Background: Recently, the management of musculoskeletal disorders with the patients' own stem cells, isolated from the walls of small blood vessels, which can be found in great numbers in the adipose tissue, has received considerable attention. On the other hand, there are still misconceptions about these adipose-derived regenerative cells (ADRCs) that contain vascular-associated pluripotent stem cells (vaPS cells) in regenerative medicine. Methods: Based on our previous publications on this topic, we have developed a concept to describe the significance of the ADRCs/vaPS cells in the field of orthobiologics as briefly as possible and at the same time as precisely as possible. Results: The ADRCs/vaPS cells belong to the group of orthobiologics that are based on autologous cells. Because the latter can both stimulate a patient’s body's localized self-healing power and provide new cells that can integrate into the host tissue during the healing response when the localized self-healing power is exhausted, this group of orthobiologics appears more advantageous than cell-free orthobiologics and orthobiologics that are based on allogeneic cells. Within the group of orthobiologics that are based on autologous cells, enzymatically isolated, uncultured ADRCs/vaPS cells have several advantages over non-enzymatically isolated cells/microfragmented fat as well as over uncultured bone marrow aspirate concentrate and cultured cells (adipose-derived stem cells, bone marrow-derived mesenchymal stem cells). Conclusions: The use of ADRCs/vaPS cells can be seamlessly integrated into modern orthopedic treatment concepts, which can be understood as the optimization of a process which - albeit less efficiently - also takes place physiologically. Accordingly, this new safe and effective type of treatment is attractive in terms of holistic thinking and personalized medicine.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, and polyacrylamides, to the promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies emerge as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

Intestinal epithelial cell activities during homeostasis and regeneration are well described, but their potential interactions with stromal cells remain unresolved. Exploring the functions of these heterogeneous intestinal mesenchymal stromal cells (iMSCs) remains challenging due to the lack of specific markers for most functionally homogenous subpopulations. In recent years, however, novel clustering techniques such as single-cell RNA sequencing (scRNA-seq), fluorescence-activated cell sorting (FACS), confocal microscope, and computational remodeling of intestinal anatomy have helped identify and characterize some specific iMSC subsets. These methods help researchers learn more about the localization and functions of iMSC populations during intestinal morphogenic and homeostatic conditions. Furthermore, it is imperative to understand their cellular pathways for activation and how they interact with surrounding cellular components, particularly during intestinal epithelial regeneration that follows mucosal injury. This review provides insights into the spatial distribution and functions of some identified iMSC subtypes in intestinal morphogenesis, homeostasis, and regeneration. We reviewed related signaling mechanisms implicated during epithelial and subepithelial stromal cell crosstalk. Future research should focus on elucidating the molecular intermediates of these regulatory pathways to open a new frontier for potential therapeutic targets that can alleviate intestinal mucosa-related injuries.

The vacuolar proton translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism is mainly based on anaerobic glycolytic reactions. Moreover, the neoplastic cells use the V-ATPase to extrude chemotherapy drugs to the extra-cellular compartment, as a drug-resistance mechanism. In glioblastoma (GBM), the most malignant and incurable primary brain tumor, the expression of this pump is upregulated, making it a new possible therapeutic target. In this work, the bafilomycin A1 induced-inhibition of V-ATPase in patients-derived glioma stem cell (GSC) lines was evaluated together with temozolomide, the first-line line therapy against GBM. In contrast with previous published data, the proposed treatment did not overcome the resistance to the standard therapy. In addition, our data showed that nanomolar dosages of bafilomycin A1 lead to the blockage of the autophagy process and cellular necrosis, making the drug unusable in models that are more complex. Nevertheless, the increased expression of V-ATPase following bafilomycin A1 suggests a critical role of the proton pump in GBM stem component, encouraging the search for novel strategies to limit its activity in order to get around the resistance to the conventional therapy.

Multilineage-differentiating stress-enduring (Muse) cells, a cell subgroup from mesenchymal stem cells (MSCs), are pluripotent cells with unique characteristics such as non-tumorigenic and pluripotent differentiation ability. After homing, Muse cells spontaneously differentiate into tissue component cells and supplement damaged/lost cells to participate in tissue repair. Importantly, Muse cells can survive in injured tissue for an extended period, stabilizing and promoting tissue repair. In addition, it has been confirmed that injection of exogenous Muse cells exerts anti-inflammatory, anti-apoptosis, anti-fibrosis, immunomodulatory, and paracrine protective effects in vivo. The discovery of Muse cells is an important breakthrough in regenerative medicine. The article provides a comprehensive review of the characteristics, sources, and potential mechanisms of Muse cells for tissue repair and regeneration. This review serves as a foundation for the further utilization of Muse cells as a key clinical tool in regenerative medicine.

Hematopoietic stem cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation have been critical in our fundamental understanding of HSC biology and developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem cell niches in the marrow. Stem cell niches, in particular, can be altered by the effects of previous treatments, aging, and paracrine effects of leukemic cells that create inhospitable bone marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem cell niches can be restored to favour normal hematopoieis may be key to reducing leukemic relapses following transplant.

Lodging poses a significant challenge to rice yield, prompting the need to identify elite alleles for lodging resistance traits to improve cultivated rice varieties. In this study, a natural population of 518 rice accessions was examined to identify elite alleles associated with plant height (PH), stem diameter (SD), stem anti-thrust (AT/S), and various internode lengths: (first (FirINL), second (SecINL), third (ThirINL), fourth (ForINL), and fifth (FifINL) internode lengths). 262 SSR markers linked to these traits were uncovered through association mapping in two environmental conditions. Phenotypic evaluations revealed striking differences among cultivars, and genetic diversity assessments showed polymorphisms across the accessions. Favorable alleles were identified for PH, SD, AT/S, and 1 to 5 internode lengths, with specific alleles displaying considerable effects. Noteworthy alleles include RM6811-160 bp on chromosome 6 (which reduces PH) and RM161-145 bp on chromosome 5 (which increases SD). The study identified a total of 42 novel QTLs. Specifically, seven QTLs were identified for PH, four for SD, five for AT/S, five for FirINL, six for SecINL, five for ThirINL, six for ForINL, and four for FifINL. QTLs qAT/S-2, qPH2.1, qForINL2.1, and qFifINL exhibited the most significant phenotypic variance (PVE) of 3.99% for the stem lodging trait. AT/S, PH, ForINL and FifINL had additive effects of 5.31 kPa, 5.42 cm, 4.27cm and 4.27cm, respectively, offering insights into eight distinct cross-combinations for enhancing each trait. This research suggests the potential for cross-breeding superior parents based on stacked alleles, promising improved rice cultivars with enhanced lodging resistance to meet market demands.

APC mutation is the main driver mechanism of CRC development and leads to constitutively activated WNT signaling, overpopulation of ALDH+ stem cells (SCs), and incomplete differentiation. We previously reported that retinoic acid (RA) receptors are selectively expressed in ALDH+ SCs, which provides a way to target cancer SCs with retinoids to induce differentiation. Hypotheses: A functional link exists between WNT and RA pathways, and APC mutation generates a WNT:RA imbalance that decreases retinoid-induced differentiation and increases ALDH+ SCs. Accordingly, to restore parity in WNT:RA signaling, we induced wt-APC expression in APC-mutant CRC cells and assessed the ability of all-trans-retinoic acid (ATRA) to induce differentiation. Notably, ATRA substantially increased expression of the WNT-target gene, CYP26A1, and inducing wt-APC reduced this expression by 50%. Thus, RA and WNT pathways crosstalk to modulate CYP26A1 metabolism of retinoids. We found that inducing wt-APC augments ATRA-induced cell differentiation by: i) decreasing cell proliferation; ii) suppressing ALDH1A1 expression; iii) decreasing ALDH+ SCs; iv) increasing neuroendocrine cell differentiation. Furthermore, NanoString profiling/bioinformatics identified a novel CYP26A1-based network that links WNT and RA signaling. Moreover, CYP26A1 inhibitors sensitized CRC cells to the anti-proliferative effect of drugs that downregulate WNT signaling. Notably. in wt-APC-CRCs, decreased CYP26A1 improves patient survival. These findings have strong potential for clinical translation.

As drone technology is rapidly becoming accessible to school children in terms of both low cost and ease-of-use, primary and secondary school teachers are beginning to consider where modern drones can play an important role in schooling. To date, there is very little empirical education research printed in the education research literature guiding innovative curriculum developers in the incipient domain of drone education. As a result, teachers interested in including emerging technologies in their classrooms are often at a loss of where to begin. Through clinical interviews with schoolteachers in the United States, our study identified five readily accessible “departure points” to include drones in contemporary STEM & vocational technology (CTE) school classrooms that help teachers address common curricular goals. Taken together, these interviews reveal that teachers using drones follow one of several distinct pathways as a first step toward achieving a widespread goal of teaching students to use modern technologies to construct, pursue, and communicate findings of fruitful research inquiries—the prevalence of which is not reflected in a comprehensive literature review. The five pathways for starting a successful drone education emerging from the interview data as dominant were: timed-racing trials; precision-flight obstacle courses; computer coding; videography; and domain-specific knowledge of drone operations laws and ethics.

This study aims to investigate the effect of banana stem fibers (BSFs) treatment with liquid smoke on changes in the micro-mechanics properties of BSFs, the tensile strength of single fibers, mor-phology, crystalline properties, and functional groups. The research used four model specimen variations, namely fiber without treatment and immersion in liquid smoke for 1, 2, and 3 hours. The BSFs with treatment was dried in an oven with a temperature of 40ºC for 30 minutes. Several tests were conducted, including a tensile test of single fiber capacity of 50N standard ASTM 3379-02, SEM observation, XRD, and FTIR test. The results showed that the highest increase in fiber strength was P2J, which was 264.21 MPa, and the lowest was TP fiber at 148.54 MPa. Fibers treatment with liquid smoke can form strong C-C elemental bonds caused by the H2O degradation process in BSFs, hence carbon atoms (C) are dense, and in conditions of excessive H2O degradation, the fiber strength will become brittle and the liquid smoke can increase the tensile strength of the fiber. The morphology of the fiber changed where the untreated fiber was covered with lignin, while the treated fiber had an elongated rectangular line pattern, porous, and the lignin was eroded. Crystalline properties in the X-ray diffractogram pattern differ between untreated and treated fibers. At an angle of 2ϴ, the lowest diffraction peak is around 160 in untreated wool, and the highest is 230 in treated fiber. The functional group of the fiber has changed where there is a difference in the wave crest between untreated and treatment fiber. The longer immersion time, the element of Carbon (C) will increase. In conclusion, treating BSFs with liquid smoke can change the physical, mechanical, and chemical properties, hence becoming a choice of composite reinforcement material in the future which is lightweight and environmentally friendly.

Intratumoral heterogeneity can exist along multiple axes: Cancer Stem Cells (CSCs)/non-CSCs, drug-sensitive/drug-tolerant states and a spectrum of epithelial-hybrid-mesenchymal phenotypes. Further, these diverse cell-states can switch reversibly among one another, thereby posing a major challenge to therapeutic efficacy. Therefore, understanding the origins of phenotypic plasticity and heterogeneity remains an active area of investigation. While genomic components (mutations, chromosomal instability) driving heterogeneity have been well-studied, recent reports highlight the role of non-genetic mechanisms in enabling both phenotypic plasticity and heterogeneity. Here, we discuss various processes underlying phenotypic plasticity such as stochastic gene expression, chromatin reprogramming, asymmetric cell division and the presence of multiple “attractors”. These processes can facilitate a dynamically evolving cell population such that a subpopulation of (drug-tolerant) cells can survive lethal drug exposure and recapitulate population heterogeneity on drug withdrawal, leading to relapse. These drug-tolerant cells can be both pre-existing and also induced by the drug itself through cell-state reprogramming. The dynamics of cell-state transitions both in absence and presence of the drug can be quantified through mathematical models. Such a dynamical systems approach to elucidating patterns of intratumoral heterogeneity by integrating longitudinal experimental data with mathematical models can help design effective combinatorial and/or sequential therapies for better clinical outcomes.

Tri-dimensional (3D) cell aggregates or spheroids are considered to be closer to physiological conditions than traditional 2D cell culture. Mesenchymal stem cells (MSCs) assembling in spheroids have increased the survival of transplanted cells. The regulation of the biological processes that maintain crucial physiological reactions of MSCs is closely related to the functioning of ion channels. The pattern of expression, role and regulatory mechanisms of ion channels could be significantly different in 3D compared to 2D culture, and, thus, needed to be properly analyzed on the level of ionic currents. We developed a specific approach that allowed us to register, for the first time, endogenous ion channels in endometrial MSCs (eMSCs) assembled in spheroids. Particularly, using the single-channel patch-clamp technique, we have recorded the activity of ion channels and observed their functional interplay in mechanosensitive clusters. Our experimental protocol could be applied for identification and studying of ion channels in 3D cell cultures.

Substantial evidence indicates that bisphenol A (BPA), a ubiquitous environmental chemical used in the synthesis of polycarbonate plastics and epoxy resins, can impair brain development. Clinical and epidemiological studies exploring potential connections between BPA and neurodevelopmental disorders in humans have repeatedly identified correlations between early BPA exposure and developmental disorders, like attention deficit/hyperactivity disorder and autism spectrum disorder. Investigations using invertebrate and vertebrate animal models have revealed that developmental exposure to BPA can impair multiple aspects of neuronal development, including neural stem cell proliferation and differentiation, synapse formation, and synaptic plasticity—neuronal phenotypes that are thought to underpin the fundamental changes in behavior associated neurodevelopmental disorders. Consistent with BPA-associated neuronal phenotypes, behavioral analyses of BPA-treated animals have shown significant impacts on behavioral endophenotypes related to neurodevelopmental disorders, including altered locomotor activity, learning and memory deficits, and anxiety-like behavior. To contextualize the correlations between BPA and neurodevelopmental disorders in humans, this review summarizes current literature reporting on the developmental neurotoxicity of BPA in laboratory animals, with an emphasis on neuronal phenotypes, molecular mechanisms, and behavioral outcomes. The collective works described here predominantly support the notion that gestational exposure to BPA should be regarded as a risk factor for neurodevelopmental disorders.

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species, but acts poorly toward non-transformed cells derived from multiple tissues. Here we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Mechanistically, HMA elicits the permeabilization of the limiting lysosomal membrane, a hallmark feature of the lysosome-dependent cell death pathway. Our observations expose a key vulnerability intrinsic to cancer stem cells, and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions that can lead to the loss of structure and/or function impairment. These changes can cause a partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, what in turn can affect the quality of life. For those reasons, PNI is a major public health concern. This review aims to revisit the concepts associated with the PNI. First, the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to explain the urge for new approaches and to understand the methods to evaluate nerve regeneration in a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

This paper presents the process of designing, fabrication, assembling, programming and optimizing a prototype of a nonlinear mechatronic Ball-Plate System (BPS) as a laboratory platform for STEM engineer education. Due to the nonlinearity and complexity of BPS, task presents challenging issues, such as: 1) difficulties in controlling the stabilization of a given position point known as steady state error, 2) position resolution known as specific distance error and 3) adverse environmental effects - light shadow error, also discussed in this paper. The laboratory BPS prototype for education was designed, manufactured and installed at the Karlovac University of Applied Sciences at the Department of Mechanical Engineering, Study of mechatronics. The low-cost two degrees BPS system uses a USB HD camera for computer vision as feedback and two DC servomotors as actuators. Due to controlling problems, an advanced block diagram of control system is proposed and discussed. An open-source control system based on Python scripts that allows the use of ready-made functions from the library allows changing the color of the ball and the parameters of the PID controller, thus indirectly simplifying control system and directly the mathematical calculation. The authors will continue their research on this BPS mechatronic platform and control algorithms.

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.

Pneumonia remains a major cause of morbidity and mortality worldwide, especially during COVID-19 pandemic. With the significant global health burden that pneumonia poses, it is es-sential to improve therapeutic and management strategies. The increasing emergence of antibiotic resistant bacterial strains limits options for effective antibiotic use. New antibiotics for treatment of pneumonia may address deficits in current antimicrobial drugs, with an ability to cover both typical, atypical, and resistance pathogen. Several of these newer drugs also have structural characteristics that allow for a decreased propensity in development of bacterial resistance. Po-tential use of stem cell therapies in place of corticosteroid treatments may also offer an im-provement in patient outcomes. Human mesenchymal stem cell treatments have shown efficacy and safety in treating COVID-19 induced pneumonia. Combined treatment with both stem cells and antibiotics in pneumonia in a rabbit model has also shown significantly increased efficacy in comparison to antibiotic treatment alone, presenting yet another possible route for a novel strategy in treating pneumonia, though additional future studies are necessary before clinical implementation. While pneumonia remains a major disease of concern, having newer approved antibiotics as well as novel therapies such as stem cell treatments in the pipeline offers clinicians more options in effectively treating pneumonia.

Formation of new blood (angiogenesis) and lymphatic (lymphangiogenesis) vessels are major events associated with most epithelial malignancies, including breast cancer. Angiogenesis is essential for cancer cell survival. Lymphangiogenesis is critical in maintaining tumoral interstitial fluid balance and importing tumor-facilitatory immune cells. Both vascular routes also serve as conduits for cancer metastasis. Intratumoral hypoxia promotes both events by stimulating multiple angiogenic/lymphangiogenic growth factors. Studies on tumor-associated lymphangiogenesis and its exploitation for therapy have received less attention from the research community than those on angiogenesis. Inflammation is a key mediator of both processes, hijacked by many cancers by aberrant expression of the inflammation-associated enzyme cyclo-oxygenase (COX)-2. In this review, we focus on breast cancer and show that COX-2 is a major promoter of both events, primarily resulting from the activation of Prostaglandin (PG) E receptor EP4 on tumor cells, tumor-infiltrating immune cells, and endothelial cells; and induction of oncogenic microRNAs. COX-2/EP4 pathway also promotes additional events in breast cancer progression, such as cancer cell migration, invasion, and stimulation of stem–like cells. Based on a combination of studies using multiple breast cancer models, we show that EP4 antagonists hold a major promise in breast cancer therapy in combination with other modalities including immune check-point inhibitors

We previously showed that, based on the frequency and distribution of specific cell types, rainbow trout (RT) intestinal mucosa is divided in two regions that form a complex nonlinear 3D pattern and have a different renewal rate. This work had two aims. First, to investigate whether the unusual distribution of cell populations reflects a similar distribution of functional activities. To this end, we determined the protein expression pattern of three well defined enterocytes functional markers: Peptide Transporter 1 (PepT1), Sodium-Glucose/Galactose Transporter 1 (SGLT-1) and fatty acid-binding protein 2 (Fabp2). Second, to characterize the structure of RT intestinal stem cells (ISC) niche and to determine whether the different proliferative rates correlate with a different organization and/or extension of the stem cells population. We studied the expression and localization of well-characterized mammal ISC markers: LGR5, HOPX, SOX9, NOTCH1, DLL1 and WNT3A. Our results indicate that morphological similarity is associated with similar function only between the first portion of the mid-intestine and the apical part of the complex folds in the second portion. Mammal ISC markers are all expressed in RT but their localization is completely different suggesting also substantial functional differences. Finally, higher renewal rates are supported by a more abundant ISC population.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been considered a promising therapeutic approach to cardiovascular disease. This study intends to compare the effect of BMSCs through a standard active cardiac support device (ASD) and intravenous injection on global myocardial injury induced by isoproterenol. BMSCs were cultured in vitro, and the transplanted cells were labeled with a fluorescent dye CM-Dil. Isoproterenol (ISO) was injected into the rats; two weeks later, the labeled cells were transplanted into ISO-induced heart-injury rats through the tail vein or ASD device for five days. The rats were sacrificed on the first day, the third day, and the fifth day after transplantation to observe the distribution of cells in the myocardium by fluorescence microscopy. The hemodynamic indexes of the left ventricle were measured before sacrificing. H&E staining and Masson’s trichrome staining were used to evaluate the cardiac histopathology. In the ASD groups, after three days of transplantation, there were many BMSCs on the epicardial surface, and after five days of transplantation, BMSCs were widely distributed in the ventricular muscle. But in the intravenous injection group, there were no labeled-BMSCs distributed. In the ASD+BMSCs-three days treated group and ASD+BMSCs -five days-treated group, left ventricular systolic pressure (LVSP), the maximum rate of left ventricular pressure rise (+dP/dt), the maximum rate of left ventricular pressure decline (-dP/dt) increased compared with model group and intravenous injection group (P<0.05). By giving BMSCs through ASD device, cells can rapidly and widely distribute in the myocardium and significantly improve heart function.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. Here we report that BeWo and HUVEC cells are permissive to ZIKV and that the impact of YFV post-vaccination antibodies on ZIKV replication is cell line dependent. Embryoid bodies are also permissive to ZIKV and the presence of YFV antibodies collected 1 to 6 months post vaccination enhances ZIKV infection. Our data show that each of the cell lines and EBs have a unique response to ZIKV complexed with post-vaccination serum suggesting there may be cell-specific mechanisms that impact congenital ZIKV infections. Since ZIKV infections can cause severe congenital syndromes, it is crucial to understand any potential enhancement or protection offered from cross-reactive, post-vaccination antibodies.

Background: This study tested the hypothesis that treatment of symptomatic, partial-thickness rotator cuff tear (sPTRCT) with fresh, uncultured, unmodified, autologous adipose derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care is safe and more effective than corticosteroid injection. Methods: Subjects aged between 30 and 75 years with sPTRCT who did not respond to physical therapy treatments for at least six weeks were randomly assigned to receive a single injection of an average 11.4×10⁶ UA-ADRCs (in 5 mL liquid; mean cell viability: 88%) (n=11; modified intention-to-treat (mITT) population) or a single injection of 80 mg of methylprednisolone (40 mg/ml; 2 mL) plus 3 mL of 0.25% bupivacaine (n=5; mITT population), respectively. Safety and efficacy were assessed using the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), RAND Short Form-36 Health Survey and pain visual analogue scale (VAS) at baseline (BL) as well as three weeks (W3), W6, W9, W12, W24, W32, W40 and W52 post treatment. Fat-saturated T2 weighted magnetic resonance imaging of the shoulder was performed at BL as well as at W24 and W52 post treatment. Results: No severe adverse events related to the injection of UA-ADRCs were observed in the 12 months post treatment. The risks connected with treatment of sPTRCT with UA-ADRCs were not greater than those connected with treatment of sPTRCT with corticosteroid injection. However, one subject in the corticosteroid group developed a full rotator cuff tear during the course of this pilot study. Despite the small number of subjects in this pilot study, those in the UA-ADRCs group showed statistically significantly higher mean ASES total scores at W24 and W52 post treatment than those in the corticosteroid group (p < 0.05). Discussion: This pilot study suggests that the use of UA-ADRCs in subjects with sPTRCT is safe and leads to improved shoulder function without adverse effects. To verify the results of this initial safety and feasibility pilot study in a larger patient population, a randomized controlled trial on 246 patients suffering from sPTRCT is currently ongoing.

This work aims to characterize a new method to recover low-manipulated human adipose tissue, enriched of adipose tissue-derived mesenchymal stem cells (ATD-MSCs) for autologous use in regenerative medicine applications. Lipoaspirated fat collected from patients was processed through Lipocell, a II-a medical device for dialysis of adipose tissue, by varying filter sizes and washing solutions. ATD-MSCs yield was measured with flow cytometry after SVF isolation in fresh and cultured samples. Purification from oil and blood was measured after centrifugation with spectrophotometer analysis. Extracellular matrix preservation was assessed through H&E staining and biochemical assay for total collagen, type-2 collagen, and GAGs quantification. Flow cytometry showed a 2-fold increase of ATD-MSCs yield in treated samples in comparison with untreated lipoaspirate; no differences where reported when varying filter size. The association of dialysis and washing thoroughly removed blood and oil from samples. Tissue architecture and extracellular matrix integrity were unaltered after Lipocell processing. Dialysis procedure associated with Ringer’s lactate preserves the proliferation ability of ATD-MSCs in cell culture. The characterization of the product shows that Lipocell is an efficient method to purify the tissue from undesired byproducts, preserving ATD-MSCs vitality and ECM integrity, resulting in a promising tool for regenerative medicine applications.

In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also has an interesting aspect as a mesenchymal stem cell reservoir. The splenic mesenchymal stem cells contribute to tissue repair in damaged tissue, and thus, the infusion can be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

We investigated the micro-threaded stem taper surface and the impact on premature failures, aseptic loosening, and infection. We have focused on the fretting, and crevice corrosion of micro-threaded tapers, as well as the characterization of microstructure and surface properties of two new and three retrieved Zweymüller stem tapers of cementless hip endoprostheses selected from a set of 45 stems. The retrievals examined were those in which the sole source of modularity with a metallic component was the head-stem taper interface between the Ti alloy taper stem and the ceramic head. To determine the surface chemistry and microstructures of both new and retrieved hip endoprostheses stem taper titanium alloy, scanning electron microscopy (SEM) was employed for morphological and microstructural analyses. At the same time, energy dispersive spectroscopy (EDS) was utilized for characterizing chemical element distribution, and electron backscattered diffraction (EBSD) was used for phase analysis. The micro-threated stem taper’s roughness for different manufacturers was investigated using an optical profilometer. Standard roughness pa-rameters Ra (average surface roughness) and Rz (mean peak to valley height of the roughness pro-file) were used in this investigation.Additionally, profile depth and peak spacing for different samples were investigated. The surface roughness results indicate no significant difference in roughness associated with varying survivorship times, ranging from 3 to 239 months, and across different manufacturers. Electrochemical studies revealed no fretting corrosion in retrieved stem tapers (ceramic head) that prematurely failed due to aseptic loosening after 239 months, infection after 3 months, and low-grade infection after a 32-month lifetime. Therefore, three retrieved ta-pers and two new ones for comparison underwent potentiodynamic measurements in Hank’s so-lution to ascertain the corrosion rate of new and retrieved stem taper surfaces. The results show a low corrosion rate for both new and retrieved samples that failed prematurely due to aseptic loosening. However, the corrosion rate of infected and low-grade infected tapers was higher. In conclusion, our study aligns with existing literature, suggesting that the use of ceramic heads de-creases the problem of taper corrosion and subsequently reduces premature failures in total hip arthroplasty.

During pregnancy, profound physiological changes occur in the maternal body, including those affecting oral health. Dental stem cells (DSCs) have emerged as promising candidates for regenerative therapies in dentistry. This manuscript delves into the intricate interplay between DSC behavior and maternal oral health during pregnancy. We provide an overview of current knowledge concerning the impact of pregnancy on DSCs, highlighting their potential roles in maintaining oral homeostasis and responding to pathological conditions. Additionally, we identify key research gaps and propose future directions for investigating novel therapeutic strategies leveraging DSCs to improve maternal and fetal oral health outcomes. By elucidating this relationship, we aim to pave the way for innovative approaches in preventive and regenerative dentistry tailored to the unique needs of pregnant women.

Efforts to enhance carbon storage in forest ecosystems through policy and management decisions rely on accurate forest biomass assessments. However, most forest inventories consider tree mortality the only form of aboveground biomass loss, overlooking other important factors, such as wood decay in living trees. In this study, using linear mixed-effects models, we delve into the sustainability of mature and over-mature deciduous forests in Latvia by conducting a comprehensive analysis of stem rot severity, identifying species for which the impact of stem rot on their carbon stock reduction was most significant. The analysis focused on determining the proportion of discolored wood, decomposed wood, and hollow spaces within the stems of 190 living deciduous trees commonly found in hemiboreal forests. The study reveals a greater extent of stem rot and more extensive decay in Populus tremula trees than in Betula spp., Alnus glutinosa, and Alnus incana. It emphasizes the influence of tree species, age, and diameter at breast height on stem rot proportions. The stump rot area significantly predicts the amount of decomposed and discolored wood within the stem. The study provides valuable insights for sustainable forestry practices and highlights challenges in estimating stem rot severity, emphasizing the need for comprehensive diagnostic methods.

Background: Although autophagy is a pro-survival process of tumor cells, in particular conditions and when differently regulated by specific signals it can stimulate cell death. We previously demonstrated that the selective stimulation of the M2 muscarinic receptor subtype (M2 mAChR) negatively controls cell proliferation and survival and causes oxidative stress and cytotoxic and genotoxic effects in both GBM cell lines and GBM stem cells (GSCs). In this work, we have evaluated whether autophagy was induced as a downstream mechanism of the observed cytotoxic processes induced by M2 mAChR activation by the orthosteric agonist APE or the dualsteric agonist N-8-Iper. Methods: To assess the activation of autophagy, we analyzed the expression of LC3B by Western blot analysis and in LC3B-EGFP transfected cell lines. Apoptosis was assessed by Caspases 3 and 9 protein expression. Results: Our data indicate that activation of M2 mAChR by N-8-Iper promotes autophagy in both U251 and GB7 cells lines as suggested by the LC3B-II expression level and analysis of the transfected cells by fluorescence microscopy. Autophagy induction by M2 mAChRs is regulated by the decreased activity of the PI3K/AKT/mTORC1 pathway and upregulated by the pAMPK expression. Downstream autophagy activation, the increase of apoptosis was also observed in both cell lines after treatment with the two M2 agonists. Conclusions: N-8-Iper treatment causes autophagy via pAMPK upregulation, followed by apoptosis in both investigated cell lines. In contrast, the absence of autophagy in APE-treated GSC cells seems to indicate that cell death could be triggered by mechanisms alternative to those observed for N-8-Iper.

Coronavirus disease-2019 (COVID-19) was seen as a respiratory disease, however, an increasing number of reports indicated that the spike protein could also be the cause of the long-term post-infectious conditions known as Long-COVID characterized by a group of unresponsive idiopathic severe neuro, cardio-vascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Parkinson's like-disease. Different lines of pieces of evidence confirmed that the spike protein that can be found on the surface of the SARS-CoV-2 virus latches onto angiotensin-converting enzyme 2 (ACE2) receptors located on target cells. The RNA genome of coronaviruses, which, has a median length of 29 kb and is the longest among all RNA viruses, is comprised of six to ten open reading frames (ORFs) that are responsible for encoding both the replicase and structural proteins for the virus. Each of the components of the viral genome is packaged into a helical nucleocapsid that is surrounded by a lipid bilayer. The viral envelope of coronaviruses is typically made up of three proteins that include the membrane protein (M), the envelope protein (E), and the spike protein (S). The spike protein not only facilitates the virus entry into healthy cells, which is the first step in infection but also promote profound damage to different organs and tissues leading to severe impairments and long-term disabilities. Here, we discussed the pervasive mechanism that spikes mRNA adopted to alter multipotent and pluripotent stem cell (SCs) genomes and the acquired disability of generating an infinite number of affected clonal cells. This stance is based on the molecular and evolutionary aspects obtained from retrotransposons-retrotransposition in mammalians and humans that documented the frequent integration of mRNA molecules into genomes and thus into DNA. Retrotransposition is the molecular process in which transcribed and spliced mRNAs are accidentally reverse-transcribed and inserted into new genomic positions to form a retrogene. Sequence-specific traits of mRNA clearly showed long interspersed element-1 (LINE-1 or L1) to confirm the retrotransposition, considered the most abundant autonomously active retrotransposons in the human genome. In mammals, L1 retrotransposons drive retrotransposition and are composed of long terminal repeats (LTRs) and non-LTR retrotransposons (mainly long interspersed nuclear elements or LINEs); specifically, the LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons. In response to retrotransposons transposition, stem cells (SCs) employ a number of silencing mechanisms, such as DNA methylation and histone modification. This manuscript theorizes the expression patterns, functions, and regulation of mRNA Spike protein imprinted by SCs retrotransposons which generate unlimited lines of affected cell progenies and tissues as the main condition of untreatable Spike-related inflammatory conditions.

Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment yet, and AD's pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second the Carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in pre-symptoms stages. Finally, we analyzed the differential expressed proteins (DEPs) for biological and functional enrichment. These proteins showed an impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways resembling previous AD reports. Our study is the first proteomic analysis in MSCs from FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.

Embryoid bodies (EBs) are multicellular three-dimensional (3D) aggregates generated from induced pluripotent stem cells (iPSCs) in suspension and serve as useful biological sources for many downstream applications. Imaging of live EBs has been hampered mainly due to the inherent limitations of the imaging techniques applied to date. This study aimed to image human iPSC (hiPSC) derived EBs to obtain their 3D volume, determining size, morphology, and cell viability from day 7 to 14 using Light Sheet Fluorescence Microscopy (LSFM). Furthermore, chromosomal stability was assessed using Multicolor fluorescence in situ hybridization (M-FISH) from day 8 to 14. EB volume increased from day 7 to 13 which, decreased at day 14. From day 7 to 11, the EBs mainly appeared spherical and morphed into an ellipsoidal shape by day 13. All EBs showed varied external morphologies and larger cavities at day 14. The EB karyotype was diploid 46XY at day 8 and exhibited a low level of aneuploidy from day 10 to 14. This study shows that an increase in cell death affects the morphology and chromosomal stability in EBs derived from hiPSC. We demonstrate that the combination of LSFM and M-FISH helps characterize EBs that will assist future stem cell therapies.

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject's individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n=232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n=37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject's age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether in-dependence of key characteristics of UA-ADRCs of the subject's individual age, sex, BMI and eth-nicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature.

Telomere repeats at the ends of human chromosomes protect chromosomes from degradation, and telomerase has a prominent role in telomere maintenance. Telomerase also affects cell proliferation, DNA replication, differentiation, and tumourigenesis. TERT (telomerase reverse transcriptase enzyme) is the catalytic subunit of telomerase and is critical for enzyme activity. TERT promoter mutations and promoter methylation are strongly associated with increased telomerase activation in cancer cells. Notably, TERT and telomerase are downregulated in stem cells during their differentiation. Therefore, the link between differentiation and telomerase provides a valuable tool for studying the epigenetic regulation of TERT enzyme. Oxygen tension affects several cellular behaviours including proliferation, metabolic activity, stemness, and differentiation. The role of oxygen tension in driving promoter modifications of the TERT gene in embryonic stem cells (ESCs) is poorly understood either in vitro or in vivo. We adopted a monolayer ESCs differentiation model to explore the role of low, physiological, oxygen (physoxia) in the epigenetic regulation of telomerase and associated genes, including TERT, DNMTs, and HDACs. Cells were cultured in either air, a 2% O2 incubator, or a 2% O2 oxygen workstation to provide a fully defined 2% O2 environment. Pre-gassed media (pre-conditioned to 2% O2 in a HypoxyCool unit) was used in all 2% O2 experimentation. As anticipated, physoxia culture increased the proliferation rate and stemness of ESCs and a slower onset of differentiation in physoxia was evident. Further, downregulated TERT expression was correlated to reduced telomerase activity during differentiation. TERT expression and telomerase activity remained significantly elevated in physoxia during differentiation. A substantial increase in TERT promoter methylation levels was noted during differentiation. Chemical inhibition of DNMT3B reduced TERT promoter methylation and was associated with increased TERT gene and telomerase activity during differentiation. DNMT3B CHiP demonstrated that downregulated TERT expression and increased proximal promoter methylation were associated with DNMT3B binding to the promoter. In conclusion, we have demonstrated that DNMT3B can directly bind TERT promoter, change its methylation levels, and contribute to regulation of telomerase activity.

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

Mineral wool made from basalt fibers is frequently used as an insulating material in construction systems. In this study, both unused mineral wool, and wool obtained from the softened roofing area, were comprehensively analyzed in a laboratory using different characterization techniques. Firstly, the amount of initial water content and compressive strength at 10% deformation were determined. Secondly, microstructure and surface chemical composition were analysed by Scanning electron microscopy (SEM) equipped with energy dispersive x-ray spectroscopy (EDX). To study heterogeneities near the fiber surface and to examine cross-sectional composition, a Scanning transmission electron microscope (STEM) was used. Finally, to verify possible reasons for resin degradation, Thermogravimetry analysis and differential scanning colometry (TGA-DSC) were simultaneously carried out. The results show that natural aging under high humidity and thermal fluctuations greatly affects the surface morphology and chemical composition of fibrous composite. Phenol-formaldehyde and other hydrophobic compounds that protect fibers against moisture and give compressive resistance were found to be degraded.

Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. For several cancers, breast and prostate in particular, bone is the primary site of metastasis. Efforts to treat bone metastases have been stymied by a lack of models to study the progression and cellular players and signaling pathways driving bone metastasis. In this review, we examine the newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic and in silico computational models bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cell enter and escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.

Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The present standard-of-care for type 1 diabetes is exogenic insulin substitutional therapy. The most advanced stretegies in this area is the development of hybrid-closed loop system and the producing of long-acting insulins. Progresses in stem cell therapies have started to revolutionize the care of patients with type 1 diabetes; however, significant challenges remain including the limited islets availability, difficulties in maintaining the viability, the heterogeneity within a complex pathology and in patients’ responses to treatment. On the way, a considerable amount of efforts in maximizing the islet transplantation effectiveness by controlling the advantageous of different stem cell approaches. With the availability and the use of big data, the concept of precision medicine is gaining wide attention worldwide and could bring the dream of “presonlaized” therapies as a reality in the near future. Here we review the current range of treatments available as well as recent pre-clinical breakthroughs in the field of personlaized medicine for type 1 diabetes.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burns healing, in the absence of regenerating epidermis, is infections which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating recruitment of macrophages into burns may contribute to faster regeneration of the epidermis and thus, decreasing the risk of infections. This review describes a unique method for rapid recruitment of macrophages into burns and activation of these macrophages to mediate accelerated regrowth of the epidermis and healing of burns. The method is based on application of bio-degradable “alpha-gal” nanoparticles to burns. These nanoparticles present multiple alpha-gal epitopes (Gal alpha1-3Gal beta1-4GlcNAc-R) which bind the abundant natural anti-Gal antibody that constitutes ~1% of immunoglobulins in humans. Anti-Gal/alpha-gal nanoparticles interaction activates the complement system, resulting in localized production of the complement cleavage-peptides C5a and C3a that are highly effective chemotactic factors for monocytes derived macrophages. The macrophages recruited into the alpha-gal nanoparticles treated burns are activated following interaction between the Fc portion of anti-Gal coating the nanoparticles and the multiple Fc receptors on macrophages cell membranes. The activated macrophages secrete a variety of cytokines/growth factors that accelerate the regrowth of the epidermis and regeneration of the injured skin, thereby cutting the healing time by half. Studies on healing of thermal injuries in the skin of anti-Gal producing mice, demonstrated a much faster recruitment of macrophages into burns treated with alpha-gal nanoparticles than in control burns treated with saline and healing of the burns within 6 days, whereas healing of control burns takes ~12 days. alpha-Gal nanoparticles are non-toxic, and do not cause chronic granulomas or keloids. These findings suggest that alpha-gal nanoparticles treatment may harness anti-Gal for inducing similar accelerated burn healing effects also in humans.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women characterized by hyperandrogenism, oligo-anovulation and insulin resistance closely linked with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS was likely further selected in humans when scarcity of food in hunter-gatherers of the late Pleistocene additionally programmed for enhanced fat storage to meet the metabolic demands of reproduction in later life. As an evolutional model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor fat storage through exaggerated lipid accumulation during development to adipocytes in vitro. In turn, fat storage is counterbalanced by reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This metabolic adaptation in PCOS balances energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction; its accompanying oligo-anovulation allowed PCOS women from antiquity sufficient time and strength for childrearing of fewer offspring with a greater likelihood of childhood survival. Heritable PCOS characteristics are now affected by today’s contemporary environment through epigenetic events that predispose to lipotoxicity with excess weight gain and pregnancy complications, calling for an emphasis on preventive healthcare to optimize the long-term, endocrine-metabolic health of PCOS women in today’s obesogenic environment.

Neurodegenerative diseases encompass a broad spectrum of profoundly disabling disorders that impact millions of individuals globally. While their underlying causes and pathophysiol-ogy display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, constitutes a shared characteristic among them. Con-sequently, targeting the BBB has emerged as an innovative therapeutic strategy for address-ing neurological diseases. Within this review, we not only explore the neuroprotective, neu-rotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will delve into the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological disorders like Alzheimer’s disease, Parkinson’s disease, and stroke as well as immune-mediated conditions such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological con-texts.

Purpose: Inflammation of various degrees is common among humans. There are associated side effects with orthodox delivery systems and anti-inflammatory agents hence the study investigated the characteristics of herbal lipospheres and the anti-inflammatory potency of the lipospheres formulated from Pentaclethra macrophylla with the view to having a drug with a better delivery system and lesser side effects.Methods: Herbal lipospheres were formulated using solidified reverse micellar solutions (SRMS) of P90H and goat fat and characterized for particle size and morphology, pH – time dependent analysis, encapsulation efficiency (EE%) and Fourier Transform infrared spectroscopy. The in vitro antinociceptive and anti-inflammatory study were carried out using membrane stabilization by hypotonicity induced haemolysis and determination of anti-platelet aggregatory activity models. The in-vivo anti-nociceptive and anti-inflammatory studies on egg albumin and formaldehyde induced arthritis models were done. Total white blood cell count and differential blood count were carried out on the rats. Results: The results showed that there was no change in pH for the PM unloaded lipospheres and 2.5g of PM-loaded lipospheres from Day 1 to Day 7, but mild variation in the rest of the formulations. The EE ranged from 35.2% to 94% increasing according to the drug concentration. The photomicrographs of the lipospheres showed that the particles were spherical in shape. The particle sizes were within the acceptable range for lipospheres. FTIR showed no interaction. In the arthritis study, PM-loaded lipospheres inhibited edema consistently throughout the duration of observation. Inhibition of membrane increased steadily with an increase in concentration of PM in the lipospheres and the standard drug. The platelet aggregatory inhibition decreased steadily with an increase in concentration of the PM in the lipospheres as well as the standard. The T50 dose of PM had the highest percentage of WBC and it decreased as the treatment doses increased from T100 to T200. There was no significant differences among the Neutrophil counts of the different groups.Conclusion: The study, therefore, showed that the methanol extract of Pentaclethra macrophylla formed efficient herbal lipospheres with antinociceptive and anti-inflammatory activities.

Ageing may be characterized by progressive loss of cognitive function as well as decrease in physical activities, in addition to change in appearance. Previously, we reported that intracerebroventricular transplantation of a human neural stem cell (NSC) line (F3) over-expressing choline acetyltransferase (F3.ChAT) gene, an enzyme responsible for acetylcholine synthesis, markedly improved cognitive function and physical activity of aged animals by enhancing acetylcholine and growth factors (GFs) and neurotrophic factors (NFs). In the present study, 10-month-old F344 rats were intravenously transplanted with F3 or F3.ChAT NSCs (1 x 106 cells) once a month to 21st month of age when the cumulative mortality reached 20%, and physical activity and learning/memory function were investigated, in addition to the analyses of brain acetylcholine concentration, and cholinergic and dopaminergic system restoration. Neuroprotective and neuroregenerative activities of stem cells were also confirmed by analyzing oxidative damages, neuronal skeletal protein, angiogenesis, brain and muscle weights, and proliferating host stem cells. Stem cells markedly improved both the cognitive (passive avoidance and water-maze performances) and physical (locomotor and rota-rod activities) functions, in parallel with the elevation of acetylcholine levels in cerebrospinal fluid and in muscles, in which F3.ChAT cells were superior to F3 parental cells. Stem cell transplantation down-regulated CCL11, leading to restoration of microtubule-associated protein 2 as well as functional markers of cholinergic and dopaminergic systems, and preserved brain and muscular capillaries, recovering muscle mass. In addition, stem cells enhanced antioxidative capacity, attenuating oxidative damage of multiple organs including muscles and the brain. The results indicate that NSCs over-expressing ChAT gene improve cognitive function and physical activity of ageing animals by protecting and recovering functions of multiple organs including cholinergic and dopaminergic systems as well as muscles from oxidative injuries through secretion of acetylcholine and GFs/NFs, increased antioxidant elements, and enhanced blood flow.

Glioblastoma multiforme (GBM) is a highly heterogeneous brain tumor with limited treatment options and a poor prognosis. Cancer stem cells (CSCs) have emerged as a critical factor in GBM resistance and management, contributing to tumor growth, heterogeneity, and immunosuppression. The transcription factor FOXM1 has been identified as a key player in the progression, spread, and therapy resistance of various cancers, including GBM. In this study, researchers conducted structure-based in silico screening to identify natural compounds that could target the DNA-binding domain (DBD) of the FOXM1 protein. Through molecular docking analyses, identified Silybin B as a potential inhibitor of FOXM1, exhibiting strong interaction with the protein. MD simulations were performed to validate the binding stability of the FOXM1-Silybin B complex. The study provides valuable insights into the potential of Silybin B as a FOXM1 inhibitor and its ability to induce senescence in GBM stem cells. These findings contribute to the development of structure-based design strategies for FOXM1 inhibitors and innovative therapeutic approaches for the treatment of Glioblastoma.

Cancer stem cells remain a challenge to isolate and characterize because of their plastic phenotype. Using a microfluidic lab-on-a-chip based on ultra-high frequency dielectophoresis, we measured the electromagnetic signature of colorectal cancer cells and demonstrated that cancer stem cells show a distinct and lower electromagnetic signature than differentiated cells. The release of extracellular vesicles from tumor cells can drive tumor progression and metastasis development. As extracellular vesicles from cancer stem cells carry more aggressive content, we treated colorectal cancer cells with these vesicles to test whether the lab-on-a-chip can detect a change in phenotype. The electromagnetic signature of treated cells is modified in comparison to untreated cells and sometimes even when no biological change is observed. The lab-on-a-chip provides rapid and relevant result without prior labeling compared to conventional biological approaches. It could be useful in the clinic for early detection of cancer stem cells in the tumor mass and for monitoring the aggressive potential of extracellular vesicles in the bloodstream in order to adapt therapeutic management and prevent relapse.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

Glioblastoma (GBM) is one of the most aggressive solid tumors, particularly due to the presence of cancer stem cells (CSCs). Today the characterization of this type of cells with an efficient, fast and low-cost method remains an issue. Hence, we have developed a microfluidic lab-on-a-chip based on dielectrophoresis (DEP) single cell electro-manipulation to measure the two crossover frequencies: f_x01 in low frequency range (below 500 kHz) and f_x02 in Ultra High Frequency range (UHF, above 50 MHz). First, in vitro conditions were investigated. U87-MG cell lines were cultured in different conditions in order to induce an undifferentiated phenotype. Then, ex vivo GBM cells from patients’ primary cell culture, were passed through the developed microfluidic system and characterized in order to reflect clinical conditions. This article demonstrates that the usual exploitation of low frequency range DEP does not allow the discrimination of the undifferentiated from the differentiated phenotypes of GBM cells. However, the presented study highlights the use of UHF-DEP as a relevant discriminant parameter. The proposed microfluidic lab-on-a-chip is able to follow the kinetic of U87-MG phenotype transformation in a CSC enrichment medium and their cancer stem cells phenotype acquirement.

Renewable resources gain increasing interest as source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014–2018). Special focus is drawn on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.

The purpose of this study was to evaluate the bioactivity and cell response of a well-characterized Nurse´s A-phase (7CaO•P2O5•2SiO2) ceramic and his effect compared to a control (tissue culture polystyrene-TCPS) on the adhesion, viability, proliferation and osteogenic differentiation of ahMSCs in vitro. Cell proliferation (Alamar Blue Assay), Alizarin Red-S (AR-s) staining, alkaline phosphatase (ALP) activity, osteocalcin (OCN) and collagen I (Col I) were evaluated. Also, field emission scanning electron microscopy (FESEM) images were acquired in order to visualise the cells and the topography of the material. The proliferation of cells growing in a direct contact with the material was slower at early stages of the study because of the new environmental conditions. However, the entire surface was colonized after 28 days of culture in growth medium (GM). Osteoblastic differentiation markers were significantly enhanced in cells growing on Nurse´s A phase ceramic and cultured with osteogenic medium (OM), probably due to the role of silica to stimulate the differentiation of ahMSCs. Moreover, calcium nodules were formed under the influence of ceramic material. Therefore, it is predicted that Nurse´s A-phase ceramic would present high biocompatibility and osteoinductive properties being a good candidate to be used as a biomaterial for bone tissue engineering.

Burn injuries have profound implications for aesthetics, functionality, and patient survival. Umbilical cord lining mesenchymal stem cells (SCL-MSCs) have emerged as a potential therapeutic approach for burn wounds due to their easy isolation, favorable differentiation capabilities, and low immunogenicity. This study aimed to evaluate the growth characteristics of SCL-MSCs and their effectiveness in treating burn wounds. Mechanical isolation was employed to extract mesenchymal stem cells from the umbilical cord lining membrane. The isolated cells underwent characterization, including analysis of HLA-E, G, and DR expression, and assessment of immunogenicity against rabbit antigens using ELISA. A rabbit model was utilized to administer burn treatment. SCL-MSCs exhibited typical morphology of mesenchymal stem cells and demonstrated robust proliferation. These cells expressed CD90, HLA-E, and HLA-G markers while lacking HLA-DR expression. Intact cells and supercrushed cell fluid displayed minimal and unstable immunogenicity. SCL-MSCs exhibited remarkable differentiation potential toward fibroblast lineages, with differentiated fibroblasts showing elevated collagen production and efficient sheet formation. In the experimental rabbit model, burn wounds covered with SCL-MSC tegaderm material plates exhibited superior healing compared to controls. The stem cell material plate area demonstrated reduced inflammatory cell counts (P &lt; 0.01) and increased fibroblast count, neovascularization, and mitotic index (P &lt; 0.01). These findings highlight the potential of SCL-MSCs as a valuable resource for burn wound research and treatment.

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined by in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was totally stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs were closer to those in humans than to those in mice.

Genetic sensorineural hearing loss and Meniere disease have been associated with rare variations in the coding and non-coding region of the human genome. Most of these variants are classified as likely pathogenic or variants of unknown significance and require functional validation in cellular or animal models. Given the difficulties to obtain human samples and the raising concerns about animal experimentation, human induced pluripotent stem cells emerge as cellular models to investigate the interaction of genetic and environmental factors in the pathogenesis of inner ear disorders. The generation of human sensory epithelia and neuron-like cells carrying the variants of interest may facilitate a better understanding of their role during differentiation. These cellular models will allow us to explore new strategies for restoring hearing and vestibular sensory epithelia as well as neurons. This review summarizes the use of human induced pluripotent stem cells in sensorineural hearing loss and Meniere disease and proposes some strategies for its application in clinical practice.

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of Coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in cardiovascular system, the clinical applications centered on the NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process based on the clinical images and mathematical modeling to assess the endothelial function and vulnerability of atherosclerotic plaque. Then, the emerging bioimaging technologies that have the potential to directly measure the arterial NO concentration were discussed, including the Raman spectroscopy and electrochemical sensor. Aside from the diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the inhaled NO therapy to treat the pulmonary hypertension and COVID-19, stem cell therapy and NO-releasing platform to treat endothelial dysfunction and atherosclerosis.

Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation which is characteristic of acute-distress-respiratory syndrome, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.

If genetic gains in wheat yield are to be achieved in today’s breeding, increasing genetic variability of cultivated genotypes is an essential requisite to meet. To this aim, alien gene transfer through chromosome engineering (CE) is a validated and sound strategy. Attempts to incorporate more than one alien segment into cultivated wheat have been rare, particularly for tetraploid durum wheat. Here we present the agronomic and quality performance of the first successful CE-mediated multiple introgression into the latter species. By assembling into 7AL, 3BS and 1AS arms of a single genotype homoeologous segments of Thinopyrum ponticum 7el1L, Aegilops longissima 3SlS, and Triticum aestivum 1DS arms, respectively, we have stacked several valuable alien genes, comprising Lr19+Sr25+Yp (leaf and stem rust resistance and a gene increasing semolina yellowness), Pm13 (powdery mildew resistance) and Gli-D1/Glu-D3 (genes affecting gluten properties), respectively. Advanced progenies of single, double and triple recombinants were field-tested across three years in a typical durum wheat growing area of Central Italy. The results showed that not only all recombinants had normal phenotype and fertility, but also that one of the triple recombinants had the highest yield through all seasons compared with all other recombinants and control cultivars. Moreover, the multiple introgressions enhanced quality traits, including gluten characteristics and semolina yellow index. Presence of effective disease resistance genes confers additional breeding value to the novel and functional CE products, which can greatly contribute to crop security and safety.

Imatinib became the standard treatment for chronic myeloid leukemia (CML) about 20 years ago, which was a major breakthrough in stabilizing the pathology and improving the quality of life of patients. However, the emergence of resistance to imatinib and other tyrosine kinase inhibitors leads researchers to characterize new therapeutic targets. Several studies have highlighted the role of histone deacetylase 6 (HDAC6) in various pathologies, including cancer. This protein effectively intervenes in cellular activities by its primarily cytoplasmic localization. In this review, we will discuss the molecular characteristics of the HDAC6 protein, as well as its overexpression in CML leukemic stem cells, which make it a promising therapeutic target for the treatment of CML.

The molecular study of fat cell development in the human body is essential for our understanding of obesity and related diseases. Mesenchymal stem/stromal cells (MSC) are the ideal source to study fat formation as they are the progenitors of adipocytes. In this work, we used human MSCs, received from surgery waste, and differentiate them into fat adipocytes. The combination of several layers of information coming from lipidomics, metabolomics and proteomics enabled comprehensive analysis of the biochemical pathways in adipogenesis. Simultaneous analysis of metabolites, lipids and proteins in cell culture is challenging due to the compound’s chemical difference so that most studies involve separate analysis with unimolecular strategies. In this study, we employed a multimolecular approach using a two–phase extraction to monitor the crosstalk between lipid metabolism and protein-based signaling in a single sample (~105 cells). We developed an innovative analytical workflow including standardization with in-house produced 13C-isotopically labeled compounds, hyphenated high-end mass spectrometry (high-resolution Orbitrap MS) and chromatography (HILIC, RP) for simultaneous untargeted screening and targeted quantification. Metabolite and lipid concentrations ranged over 3-4 orders of magnitude and were detected down to the low fmol (absolute on column) level. Biological validation and data interpretation of the multiomics workflow was performed based on proteomics network reconstruction, metabolic modelling (MetaboAnalyst 4.0) and pathway analysis (OmicsNet). Comparing MSCs and adipocytes, we observed significant regulation of different metabolites and lipids such as triglycerides, gangliosides and carnitine with 113 fully reprogrammed pathways. The observed changes are in accordance with literature findings dealing with adipogenic differentiation of MSC. These results are a proof of principle for the power of multimolecular extraction combined with orthogonal LC-MS assays and network construction. Considering the analytical and biological validation performed in this study, we conclude that the proposed multiomics workflow is ideally suited for comprehensive follow-up studies on adipogenesis and is fit for purpose for different applications.

The heat and matter transfer during glucose catabolism in living systems and their relation with entropy production are a challenging subject of the classical thermodynamics applied to biology. In this respect, an analogy between mechanics and thermodynamics has been performed via the definition of the entropy density acceleration expressed by the time derivative of the rate of entropy density and related to heat and matter transfer in minimum living systems. Cells are regarded as open thermodynamic systems that exchange heat and matter resulting from irreversible processes with the intercellular environment. Prigogine’s minimum energy dissipation principle is reformulated using the notion of entropy density acceleration applied to glucose catabolism. It is shown that, for out-of-equilibrium states, the calculated entropy density acceleration is finite and negative and approaches as a function of time a zero value at global thermodynamic equilibrium for heat and matter transfer independently of the cell type and the metabolic pathway. These results could be important for a deeper understanding of entropy generation and its correlation with heat transfer in cell biology with special regard to glucose catabolism representing the prototype of irreversible reactions and a crucial metabolic pathway in stem cells and cancer stem cells.

Cost-effective and functionalized scaffolds are in high demand for stem-cell-based regenerative medicine to treat refractory bone defects in craniofacial abnormalities and injuries. One potential strategy is to utilize pharmacological and cost-effective plant polyphenols and biocompatible proteins, such as gelatin. Nevertheless, the use of chemically modified proteins with plant polyphenols in this strategy has not been standardized. Here, we demonstrated that gelatin chemically modified with epigallocatechin gallate (EGCG), the major catechin isolated from green tea, can be a useful material for dedifferentiated fat cells and adipose-derived stem cells and can induce bone regeneration in a rat congenial cleft-jaw model in vivo. Vacuum-heated gelatin sponge modified with EGCG (vhEGCG-GS) induced superior osteogenesis from these two cell types compared with vacuum-heated gelatin sponge (vhGS). The EGCG-modification converted the water wettability of vhGS to a hydrophilic property (contact angle: 110° to 3.8°) and the zeta potential to a negative surface charge; the modification enhanced the cell adhesion property and promoted calcium phosphate precipitation. These results suggest that the EGCG-modification with chemical synthesis can be a useful platform to modify the physicochemical property of gelatin. This alteration is likely to provide a preferable microenvironment for multipotent progenitor cells, inducing superior bone formation in vivo.

The design of biomaterial platforms able to release bioactive molecules is mandatory in tissue repair and regenerative medicine. In this context, electrospinning is a user-friendly, versatile and low-cost technique, able to process different kinds of materials in micro- and nano-fibers with a large surface area-to-volume ratio for an optimal release of gaseous signalling molecules. Recently, the antioxidant and anti-inflammatory properties of the endogenous gasotramsmitter hydrogen sulfide (H2S), as well as its ability to stimulate relevant biochemical processes on the growth of mesenchymal stem cells (MSC), have been investigated. Therefore, in this work, new poly(lactic) acid fibrous membranes (PFM), doped and functionalized with H2S slow-releasing donors extracted from garlic, were synthetized. These innovative H2S-releasing mats were characterized for their morphological, thermal, mechanical and biological properties. Their antimicrobial activity and effects on the in vitro human cardiac MSC growth, either in the presence or in the absence of oxidative stress, were here assessed. On the basis of the results here presented, these new H2S-releasing PFM could represent promising and low-cost scaffolds or patches for biomedical applications in tissue repair.

The “stem cells” discipline represents one of the most dynamic areas in biomedicine. While adult marine/aquatic invertebrate stem cell (MISC) biology is of prime research and medical interest, studies on stem cells from organisms outside the classical vertebrate (e.g., human, mouse, zebrafish) and invertebrate (e.g., Drosophila, Caenorhabditis) models have not been pursued vigorously. Marine/aquatic invertebrates constitute the largest biodiversity and the widest phylogenetic radiation on Earth, from morphologically simple organisms (e.g. sponges, cnidarians), to the more complex mollusks, crustaceans, echinoderms and protochordates. These organisms illustrate a kaleidoscope of MISC-types that participate in the production of a large number of novel bioactive-molecules, many of which are of significant potential interest for human health. MISCs further participate in aging and regeneration phenomena, including whole-body regeneration. For years, the European MISC-community has been highly fragmented and scarce ties were established with biomedical industries in attempts to harness MISCs for human welfare. Thus, it is important to: i) consolidate the fragmented European community working on MISCs; ii) promote and coordinate European research on MISC biology; iii) stimulate young researchers to embark on research in MISC-biology; iv) develop, validate, and network novel MISC tools and methodologies; v) establish the MISC discipline as a forefront interest of biomedical disciplines, including nanobiomedicine; vi) establish collaborations with industries to exploit MISCs as sources of bioactive molecules. In order to fill the recognised gaps, the EC-COST Action 16203 “MARISTEM”, has recently been launched. At its initial stage the consortium unites 26 scientists from EC countries, Cooperating countries and Near Neighbor Countries.

Thyrotropin releasing hormone (TRH; pGlu-His-Pro-NH2) is an intercellular signal produced mainly by neurons. Among the multiple pharmacological effects of TRH, that on food-intake is not well understood. We review data that show that peripheral injection of TRH generally produces a transient anorexic effect, discuss the pathways that might initiate this effect, and explain its short half-life. In addition, central administration of TRH can produce anorexic or orexigenic effects, depending on the site of injection, that are likely due to interaction with TRH receptor 1. Anorexic effects are most notable when TRH is injected into the hypothalamus and the nucleus accumbens, while the orexigenic effect has only been detected by injection into the brain stem. Functional evidence suggests that TRH neurons that are prime candidate vectors for TRH action on food-intake include the caudal raphe nuclei projecting to the dorsal motor nucleus of the vagus, and possibly TRH neurons from the tuberal lateral hypothalamus projecting to the tuberomammillary nuclei. For other TRH neurons, the anatomical or physiological context and impact of TRH in each synaptic domain are still poorly understood. The manipulation of TRH expression in well-defined neuron types will facilitate the discovery of its role in food-intake control in each anatomical scene.

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the amyloid precursor protein (APP) gene. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.

Functional articular cartilage regeneration remains an unmet medical challenge, increasing the interest for innovative biomaterial-based tissue engineering (TE) strategies. Hydrogels, 3D macromolecular networks with hydrophilic groups, present articular cartilage-like features such as high water content and load-bearing capacity. In this study, 3D porous polyethylene glycol diacrylate (PEGDA) hydrogels were fabricated combining the gas foaming technique and an UV-based crosslinking strategy. The 3D porous PEGDA hydrogels were characterized in terms of their physical, structural and mechanical properties. Our results showed that the size of the hydrogels pores can be modulated by varying the initiator concentration. In vitro cytotoxicity tests showed that 3D porous PEGDA hydrogels presented high biocompatibility both with human chondrocytes and osteoblast-like cells. Importantly, the 3D porous PEGDA hydrogels supported the viability and chondrogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs)-based spheroids as demonstrated by the positive staining of typical cartilage extracellular matrix (ECM) (glycosaminoglycans (GAGs)) and upregulation of chondrogenesis marker genes. Overall, the produced 3D porous PEGDA hydrogels presented cartilage-like mechanical properties and supported MSC-spheroid chondrogenesis, highlighting their potential as suitable scaffolds for cartilage TE or disease modelling strategies.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigates B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq Tannic acid / 100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq Chlorogenic acid / 100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods; our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and Berberine - Berberine sulfate hydrate (BS) - investigated on Daphnia sp reported significant BS toxicity after 24 h; BVE revealed considerable toxicity after 48 hours and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated on different tumor cell lines after 24 and 48 hours of treatments. The MTS assay evidenced a dose- and time-dependent antiproliferative activity, higher on BS than BVE. The strongest diminution of tumor cell viability was recorded on breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 &lt; 100 µg/mL). However, no cytotoxicity was reported on normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE's concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

Background: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with „no-option“ critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agent’s pharmacotherapy related to the therapeutic efficacy of BMCs treatment. Methods: In the present study, we have reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 ml of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (n=22) were considered responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (n=13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors and the risk of major amputation. Results: Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI) and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP ˃ 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (n=22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (n=20) had significantly reduced pain scale after BMCs transplant, compared to the NON-RAS group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (n=17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. Conclusions: CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responder and previous treatment before BMCs transplant with RAS-acting agents alone or atorvastatin were significant.

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now known also as a modulator of gene expression. What is important for cancer, is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts the enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, including NFκB, to their cognate sites to enable expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which have a significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. In general, the capacity of cancer cells to adapt to oxidative stress depends on molecular systems such as the interface of OGG1 with NFκB, which bestows a cancer cell with the molecular mechanism of transformation of its microenvironment to enable adaptation and survival of malignant clones.

Recent advancements in experimental and computational methods for RNA secondary structure detection have revealed the crucial role of RNA structural elements in diverse molecular processes within living cells. It has been demonstrated that the secondary structure of the entire viral genome is often responsible for performing crucial functions in the viral life cycle and also influences virus evolution. To investigate the role of viral RNA secondary structure, alongside experimental techniques, the use of bioinformatics tools is important for analyzing various secondary structure patterns, including hairpin loops, internal loops, multifurcations, external loops, bulges, stems, and pseudoknots. Here, we have introduced a Python package for analyzing RNA secondary structure elements in viral genomes, which includes the recognition of common secondary structure patterns, the generation of descriptive statistics for these structural elements, and the provision of their basic properties. We applied the developed package to analyze the secondary structures of complete viral genomes collected from the literature, aiming to gain insights into viral function and evolution. Both the package and the collection of secondary structures of viral genomes are available at http://github.com/KazanovLab/RNAsselem.

Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from PGC-1α-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. Upon achieving a cellular confluence of 70-80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vivo mouse models. In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to control-secretome (Ctrl-Sec). In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum pro-inflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec-treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, OPA1 (a mitochondrial function marker), and PPARα (an anti-fibrogenic marker) in the PGC-Sec-treated group, along with reduced Collagen 1A expression (a pro-fibrogenic marker). These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

Diseases of cereals caused by pathogenic fungi can significantly reduce crop yields. Many cultures are exposed to them. The disease is difficult to control on a large scale, thus one of the relevant approaches is the crop field monitoring, which helps to identify the disease at an early stage and take measures to prevent its spread. One of the effective control methods is disease identification based on the analysis of digital images with the possibility of obtaining them in field conditions using mobile devices. In this work, we propose a method for the recognition of five fungal diseases of wheat shoots (leaf rust, stem rust, yellow rust, powdery mildew, and septoria), both separately and in combination, with the possibility of identifying the stage of plant development. A set of 2414 images of wheat fungi diseases (WFD2020) was generated, for which expert labeling was performed by the type of disease. WFD2020 data are available freely at http://wfd.sysbio.ru/. In the process of creating this set, a method was applied to reduce the degeneracy of the training data based on the image hashing algorithm. The disease recognition algorithm is based on the convolutional neural network with the EfficientNet architecture. The best accuracy (0.942) was shown by a network with a training strategy based on augmentation and transfer of image styles. The recognition method was implemented by the authors as a bot on the Telegram platform, which allows assessing plants by lesions in the field conditions.

The peril of a 3-dimensional, robust and sustained myocardial restoration by means of Tissue Engineering is that it still remains a largely experimental approach. Prolific protocols have been developed and tested in small and large animals, but as clinical cardiac surgeons, we have not come to the privilege of utilizing any of them in our clinical practice. The question arises: why? The heart is a unique organ, anatomically and functionally. It is not an easy target to replicate with current techniques, or even to support its viability and function. Currently available therapies fail to reverse the loss of functional cardiac tissue, the fundamental pathology remains unaddressed and a heart transplantation is an ultima ratio treatment option. Owing to equivocal results of cell-based therapies, several strategies have been pursued to overcome limitations of the current treatment options. Preclinical data as well as first-in-human studies conducted to date have provided important insights into the understanding of injection-based approaches for myocardial restoration. In the light of the available data, injectable biomaterials suitable for transcatheteter delivery appear to have the highest translational potential,. This article presents a current state-of-the-art in the field of hydrogel-based myocardial restoration therapy.

Background Oil palm (OP), Elaeis guineensis , is by far the most important global oil crop, supplying about 40% of total traded vegetable oil. Palm oils are key dietary components consumed daily by over three billion people, mostly in Asia, and also have a wide range of important non-food uses including in cleansing and sanitising products. Main body Oil palm is a perennial crop with a >25-year life cycle and an exceptionally small land footprint compared to annual oilseed crops. Oil palm crops globally produce an annual 81 million tonnes (Mt) of oil from about 19 million hectares (Mha). In contrast, the second and third largest vegetable oil crops, soybean and rapeseed, yield a combined 84 Mt oil but occupy over 163 Mha of increasingly scarce arable land. Despite this advantage, oil palm has acquired a poor environmental reputation, especially in Europe and North America, although soybean planting is now responsible for more deforestation. Oil palm crops face other challenges in the 2020s. On the demand side, these include changing consumer purchasing habits, threats to global trade systems, and diminishing demand for liquid fuels as transport systems become increasingly electrified. On the supply side, major issues include stagnant yields in ageing plantations, sluggish replanting of improved varieties, labour shortages, diseases and climatic/ environmental threats. The latter include the increasing incidence of new and existing pests/diseases and a general lack of climatic resilience, especially relating to elevated temperatures and increasingly erratic rainfall patterns. This review surveys the oil palm sector in the 2020s and beyond, its major challenges and options for future progress. Conclusions Oil palm crops face many future challenges, including emerging threats from climate change and new pests and diseases, that require more effective international collaboration. Nevertheless, new breeding technologies are providing the promise of improvements, such as much higher yielding varieties, improved oil profiles, enhanced disease resistance and modified crop architecture to enable harvesting mechanisation. The industry also needs to redouble its efforts to engage with global consumers in a constructive dialogue aimed at addressing its image problem and explaining the many benefits of its products.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-5 cytokine and infiltration of eosinophils. Humanized monoclonal antibodies targeting IL-5 or its receptor, represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in CRS patients is associated to the epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their typical phenotype acquiring a mesenchymal phenotype. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered in EMT during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these altered signaling pathways are able to interfere with EMT; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells which can be easily isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to delineating inflammatory process underlying the development of nasal polyps.

G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.

Interdisciplinary STEM and STEAM education give us an opportunity for creativity and educational innovation in a world scenario that needs training in which students can achieve all educational objectives and are prepared to achieve sustainable development. The rural environment with its land is a scenario that provides us with a range of educational resources for the development of STEM and STEAM projects in which students who are better trained and prepared for the needs of today's world are developed, as well as students who are more linked and sensitized to the environment, with the rural environment and its land, so important in our time.  In this article, we will collect examples from Latin America; STEM projects are being developed in which young people establish links with their environment, territory, and the local environment surrounding them. We must look carefully at projects and works in which students' ties with their land and environment are valued through the STEM and STEAM education necessary today. In this scenario, a comparison has been made between Latin American countries and Spain.

Treatment of tendinopathies with multipotent mesenchymal stromal cells (MSCs) is a promising option in equine and human medicine. However, conclusive clinical evidence is lacking. The purpose of this study was to gain insight into clinical treatment efficacy and to identify suitable outcome measures for larger clinical studies. Fifteen horses with early naturally occurring tendon disease were assigned to intralesional treatment with allogeneic adipose-derived MSCs suspended in serum or with serum alone by block randomization (dosage adapted to lesion size). Clinicians and horse owners remained blinded to the treatment during 12 months (7 horses per group) and 18 months (7 MSC- and 5 control-group horses) of follow-up including clinical examinations and diagnostic imaging. Clinical inflammation-, lameness- and ultrasonography scores improved more over time in the MSC-group. The lameness score difference significantly improved in the MSC- compared to the control-group after 6 months. In the MSC-group, 5 out of 7 horses were free of re-injuries and back to training until 12 and 18 months. In the control-group, 3 out of 7 horses were free of re-injuries until 12 months. These results suggest that MSCs are effective for treatment of early phase tendon disease and provide a basis for a larger controlled study.

Tissue regeneration is an essential requirement for wound healing and recovery of organs’ dysfunction. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium. In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity in a concentration-dependent manner. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. The results indicate that ERCM from AMSCs containing a large amount of GFs and NFs improve wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment modality, frequently applied in patients suffering from haematological malignancies. In the last two decades, there have been multiple randomised controlled trials (RCTs), review articles, and meta-analyses addressing the efficacy of rabbit anti-thymocyte globulin (r-ATG) as a graft-versus-host disease (GvHD) prophylaxis. Nevertheless, only a few aimed to compare the effectiveness of different r-ATG formulations. We performed a systematic literature review of articles published since 2017 to this day utilising PubMed, Scopus, Cochrane, and MEDLINE, with the main endpoints being prophylaxis of acute GvHD (aGvHD) and chronic GvHD (cGvHD). We subjected to scrutiny a total of 5 studies, of which 4 compared the differences between Thymoglobulin (ATG-T) and Grafalon (ATG-G), and 1 discussed the impact of ATG-T dose. Overall cGvHD, aGvHD grades II-IV, TRM, OS, NRM, LFS, relapse, overall infections, and EBV reactivation do not seem to be affected by the type of utilised rATG. However, data on aGvHD grades III-IV, GRFS, moderate-severe cGvHD, and CMV reactivation is conflicting. Through our research, we sought to summarise the most recent findings concerning r-ATGs in allo-HCT, and provide insight into the differences between the targets and origin of various ATG formulations.

Acute and chronic bone infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), remains a major complication and therapeutic challenge. It is documented that local administration of vancomycin offers better results than the usual routes of administration (e.g. intravenous) when ischemic areas are present. In this work, we evaluate the antimicrobial efficacy against S. aureus and S. epidermidis and analyzed the potential cytotoxic effect of a novel hybrid 3D-printed scaffold based on poly(caprolactone) and chitosan loaded with different vancomycin concentrations (1, 5, 10 and 20%). For this purpose, vancomycin release was measured by means of HPLC, and the biological response of ah-BM-MSCs in the presence of the scaffolds was evaluated in terms of cytotoxicity (LDH activity), proliferation (AlamarBlueⓇ) and osteogenic differentiation (ALP activity, Alizarin Red staining). In addition, two cold plasma treatments were evaluated to improve the adhesion of hydrophobic polymers to hydrogels. The hybrid PCL/CS/Van scaffolds tested were found to be biocompatible, bioactive, and bactericide, as demonstrated by no cytotoxicity or functional alteration and by bacterial inhibition. Our results suggest that the scaffolds developed would be excellent candidates to be used in a wide range of biomedical fields such as drug delivery systems or tissue engineering applications.

Differentiation of induced pluripotent stem cells to a range of useful, mature target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, organoids expressed ACE2 capable of binding SARS-Cov2 spike protein demonstrating the physiological relevance of the organoids produced. This study demonstrates the rapid production of pulmonary organoids using a multi-germ layer approach that could be used for studying novel respiratory disease interactions.

It has become practically impossible to survey the literature on cells derived from adipose tissue with the aim to apply them in regenerative medicine. The aim of this review is to provide a jump start to understanding the potential of UA-ADRCs (uncultured, unmodified, fresh, autologous adipose derived regenerative cells isolated at the point of care) in regenerative medicine. We show that serious and adequate clinical research demonstrates that tissue regeneration with UA-ADRCs is safe and effective. ADRCs are neither 'fat stem cells' nor could they exclusively be isolated from adipose tissue, as ADRCs contain the same adult (depending on the definition) pluripotent or multipotent stem cells that are ubiquitously present in the walls of small blood vessels. Of note, the specific isolation procedure used has significant impact on the number and viability of the cells and hence on safety and efficacy of UA-ADRCs. Furthermore, there is no need to further separate adipose-derived stem cells (ASCs) from ADRCs if the latter were adequately isolated from adipose tissue. Most importantly, UA-ADRCs have the physiological capacity to adequately regenerate tissue without need for manipulating, stimulating and/or (genetically) reprogramming the cells for this purpose. Tissue regeneration with UA-ADRCs fulfills the criteria of homologous use.

Publicly-funded scientists have a responsibility to engage with the public on scientific information, but are lacking a standardized framework and assessment strategy to do it well. The PEPS (Public Engagement Practices for Scientists) Method is an outcomes-centered framework employing standardized pedagogical methods with quantifiable outcomes. This approach reveals that scientists often have unrealistic expectations for achieving affective learning outcomes (i.e. changing views from anti- to pro-vaccine) by solely cognitive learning strategies (i.e. supplying data). The PEPS Method can serve as a roadmap for standardized science communication assessments, complementing existing science communication training programs for the next generation of scientists.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

Tissue regeneration is an essential requirement for wound healing and recovery of organs’ function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.

Anterior-tooth (ANT) contacts induce short latency reflex inhibition of human jaw-closing muscles. The jaw is a rigid class 1 lever for pinpoint-targeting muscle force into a single bite-point, the pivoting food particle. See-saw reflex movements around the food particle fulcrum multiply the food-crushing force. Unpredictable jolts of reaction force caused by food-crushing are subjected to the rostral ANT and caudally to the two articulate ends of the jaw triangle. Compression/distraction strains of food-crushing must be monitored and inhibited by withdrawal reflexes. The mesencephalic ganglion (Vmes), neural myelin sheath, and muscle stretch receptors evolved subsequently to the advent of jaws to improve the velocity of proprioceptive and withdrawal reflexes. In mammalians, the spindles of the taut motor units, stretched by the food-fulcrum send excitatory monosynaptic feedback for the efferent neurons of the respective ipsilateral muscle units, via Vmes. In the Vmes, the spindle-input-mediating afferent neurons are coupled with another source of afferent feedback, which is also excitatory, from the back-tooth (BAT) mechanoreceptors. The two sources of excitatory pulses are summated and targeted for the efferent neurons to boost the stretched and taut motor units. Likewise, the afferent feedback from ANT mechanoreceptors is also coupled in the Vmes with concomitant feedback from spindles. The ANT output, however, is inhibitory to negate the excitatory feedback from the stretched jaw-muscle units. The inhibitory feed from ANT temporarily blocks the excitatory potential of masticatory motor efferent neurons to protect the ANT and jaw-joints from inadvertent strains. The inhibitory inputs from ANT alternate with the excitatory inputs from BAT to determine which jaw-closing muscle units are activated or inhibited at any given instant of food-crushing. The Vmes exists in all jawed vertebrates, and its’ evolution was probably motivated by demands for the control of bite force. The monosynaptic unilateral food-crushing excitatory and inhibitory reflexes (UFCR) override the coexisting bilaterally executed feed for jaw muscles from the central nervous system. Hypothesis: The Vmes-mediated UFCR combine neural inputs from tooth contacts with concomitant feedback from muscle stretch receptors for the control of mammalian food-crushing bite force.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

The editorial explores the realm of emerging translational research in neurology and psychiatry, providing insights into various subjects, including neurodegenerative disorders and innovative therapeutic methods. The main objective is to study neurological and psychiatric disorders, such as Alzheimer's disease, with a particular emphasis on techniques for neural regeneration and repair. The editorial highlights the importance of taking a comprehensive approach to studying and treating complex neurological and psychiatric conditions. This involves thoroughly reviewing research papers on the causes, development, biomarkers, and treatment options for these conditions. The editorial emphasizes the necessity of using multidisciplinary and integrative methods to gain a deeper understanding and improve the treatment of these conditions. The development of an animal model for recurrent primary dysmenorrhea showcases the innovative techniques employed in the investigation of gynecological disorders, illustrating the capacity of translational research to connect fundamental scientific knowledge with practical medical applications. The cooperative endeavors of researchers and clinicians emphasized in this editorial lay the foundation for revolutionary advancements that hold the potential to enhance outcomes for individuals afflicted with neurological and psychiatric disorders globally.

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs), or antimicrobial peptides (AMPs) together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this communication, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition.

Acute myeloid leukemia (AML) is the second common hematologic malignancy in children. The incidence of childhood AML is much lower than acute lymphoblastic leukemia (ALL), which makes the childhood AML a rare disease in children. The role of genetic abnormalities in AML classification, management and prognosis prediction is much more important than before. The WHO classification of myeloid neoplasms and the European LeukemiaNet (ELN) classification were both revised in 2022. The application of the new information in childhood AML will be upcoming in the next few years. The frequency of each genetic abnormality in adult and childhood AML is different, therefore, in this review we emphasize in well-known genetic subtypes in childhood AML, including Core-binding factor AML (CBF AML), KMT2Ar (KMT2A/11q23 rearrangement) AML, normal karyotypes AML with somatic mutations, unbalanced cytogenetic abnormalities AML, NUP98 11p15/NUP09 rearrangement AML and acute promyelocytic leukemia (APL). Current risk group classification, management algorithm in childhood AML and novel treatment modalities, such as targeted therapy, immune therapy, chimeric antigen receptor (CAR) T-cell therapy are reviewed. Finally, the indications of hematopoietic stem cell transplantation (HSCT) in AML are discussed.

Bone tissue engineering has developed significantly in recent years as the increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cells transplantation, may hold promise as stroke therapy because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria, potentially transferrable into ischemic cells, may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells, to critically evaluate the potential of mitochondria-based stem cell therapy for stroke.

As a matter of course, the first gene must be formed in the absence of gene. On the other hand, many biopolymers including gene are produced under the genetic system in extant organisms. Thus far, no idea explaining how the first gene was formed in the absence of gene, has been proposed except the idea based on the GADV hypothesis. GADV means four amino acids; Gly [G], Ala [A], Asp [D] and Val [V]. In this article, a reliable answer to the question, how the first gene was generated, is provided. The idea is as follows. The first gene (genetic information) was formed by random joining of anticodons, GNCs, which were carried by primeval anticodon stem-loop (AntiC-SL) tRNAs produced during repeated cycles of random joining of nucleotides and degradation of oligonucleotides. However, it might be difficult for many persons to accept the idea, because tRNAs and metabolic pathways using various proteins, which are produced under genetic functions, must be used to form the first gene. Then, it is reconsidered based on definition of genetic information and minimum necessary things to generate the first gene in this article, how the first gene was generated. Consequently, it could be reconfirmed that five prototypes of members (genetic code, tRNA, metabolism, cell structure and protein) composing the fundamental life system, except gene, are certainly necessary to generate the first gene. Namely, it can be concluded that the first gene was formed through nucleotide metabolism with immature [GADV]-proteins, primeval AntiC-SL tRNA formation with immature [GADV]-proteins, formations of single-stranded (GNC)n codon sequence by random joining of anticodons, GNCs, carried by AntiC-SL tRNAs, double-stranded (ds)-(GNC)n RNA and maturation of an immature [GADV]-protein, which was produced from one strand of the ds-RNA. Thus, the first gene was formed using the five primitive or prototypes of members, which were produced in the absence of gene. There would be no other way for generating the first gene.

Background: The ageing process starts in the center of the face, in the periocular region and around the mouth, with a combination of volume loss and tissue descent, wrinkles deepen, and loss of skin structure and quality. Recently, several studies proved the efficacy of therapies based on the autologous adipose tissue grafting that leverages the properties of stromal vascular fraction (SVF) and adipose derived mesenchymal stem cells (ADSCs) to accelerate the regenerative processes of the skin. This study aimed to verify the ability of the guided Superficial Enhanced Fluid Fat Injection (SEFFI) in the facial area to correct volume loss and skin aging and proved the very low rate of complications of this standardized procedure . Methods: we retrospectively collected data from 2,365 procedures performed in Italian centers between 2019 and 2021. Guided SEFFI was performed alone or combined with cosmetic treatments, including the use of hyaluronic acid filler, suspension threads, synthetic calcium hydroxylapatite, botulin toxin, and microneedling. Results: SEFFI was used alone in more than 60% of the patients, and in all face areas. In about one tenth of patients SEFFI was combined with botulin toxin treatment or hyaluronic acid filling. Other procedures were used more rarely. Ecchymosis in the donor or injection sites was the most frequent event, and yet observed in only 14.2% and 38.6% of patients, respectively. Conclusions: The SEFFI technique is standardized and minimally invasive, leading to very few complications. It can be a promising antiaging medical treatment that combines effectiveness, safety, and simplicity.

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

The mushroom industry generates large amounts of stems, a co-product with valuable sensory and health characteristics. This work aimed to study the influence of particle size (L — &gt;0.510 mm; LI — 0.510-0.315 mm; SI—0.315-0.180 mm; S — &lt;0.180 mm) and species in the characterization and antioxidant activity of flours from stems of Agaricus bisporus (ABSF) and Pleurotus ostreatus (POSF). ABSF was rich in protein (14 g/100 g), calcium (428.23-700.77 mg/100 g), and sorbitol (22.57-26.60 g/100 g), while POSF in β-glucans (36.62-40.34 g/100 g) and linoleic acid (20.57-39.86 g/100 g of lipid). Both species were flush in amino acids with umami flavor. The highest hydration properties and oil holding capacity were exhibited in the S size of both species. ABSF showed elevated values for emulsifying activity than POSF. ABSF-S recorded the heightened antioxidant capacity in vitro, in consonance with the total phenolic compounds (0.91 mg/g). However, this antioxidant assays in POSF presented a positive correlation with β-glucans content. According to these results, there could be several food applications for these co-products, such as emulsifier stabilizer, sweetener or fortifier in the development of functional food.

The evaluation of HAADF-STEM images of a sample with the composition Nb18W16O93 provided new insights in its real structure. The basic structure comprises an intact octahedral framework of the tetragonal tungsten bronze (TTB) type. The partial occupation of the pentagonal tunnels (PT) by metal-oxygen strings determines the oxygen to metal ratio (O/SM with M = Nb,W). For a large area, the O/SM was determined to be 2.755 which is smaller than the value of Nb18W16O93 which is O/SM = 2. 735. To a large extent, the threefold TTB superstructure structure of Nb8W9O47 with a high oxygen content is present (O/SM = 2.765). In addition, a new fourfold TTB superstructure was found in small domains: Nb12W11O63 with an O/SM = 2.739 obviously accommodates a part of the sample’s metal excess compared to the stable phase Nb8W9O47.