Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.

Recent studies have indicated that hindbrain [fourth ventricle (4V)] administration of the neurohypophyseal hormone, oxytocin (OT), reduces body weight, energy intake and stimulates interscapular brown adipose tissue temperature (T_IBAT) in male diet-induced obese (DIO) rats. What remains unclear is whether chronic hindbrain (4V) OT can impact body weight in female high fat diet-fed (HFD) rodents and whether this involves activation of brown adipose tissue (BAT). We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of interscapular brown adipose tissue (IBAT) contributes to its ability to activate BAT and reduce body weight in female high HFD-fed rats. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of T_IBAT and reduction of body weight in DIO rats. We first measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (0.5, 1, and 5 µg ≈ 0.5, 0.99, and 4.96 nmol) to stimulate T_IBAT in female HFD-fed rats. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) stimulated T_IBAT similarly between sham rats and denervated rats (P=NS). We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day ≈ 16.1 mg/day) or vehicle infusion to reduce body weight, adiposity and energy intake in female HFD-fed rats (N=7-8/group). Chronic 4V OT reduced body weight gain (sham: -18.0±4.9 g; denervation: -15.9±3.7 g) and adiposity (sham: -13.9±3.7 g; denervation: -13.6±2.4 g) relative to vehicle treatment (P<0.05) and these effects were similar between groups (P=NS). These effects were attributed, in part, to reduced energy intake evident during weeks 2 (P<0.05) and 3 (P<0.05). To test whether these results translate to other female rodent species, we also examined the effect of chronic 4V infusion of OT on body weight and adiposity in two strains of female HFD-fed mice. Similar to what we found in the HFD-fed rat model, we also found that chronic 4V OT (16 nmol/day) infusion resulted in reduced body weight gain, adiposity and energy intake in female DIO C57BL/6J and DBA/2J mice (P<0.05 vs vehicle). Together, these findings suggest that 1) sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and weight loss in female HFD-fed rats and 2) the effects of OT to elicit weight loss translate to other mouse models of diet-induced obesity (DIO).

(1) Background: Allergic reactions and angioedema are important immunologic conditions in acute care settings. Prior data indicate an association between the severity of symptoms and maximum lysis (ML) in thromboelastography. We aimed to evaluate the dynamics of ML after two hours of observation after admission to the emergency department. (2) Methods: We deter-mined ML with thromboelastography using extrinsic testing (EXTEM, ROTEM®, Werfen GmbH, Munich, Germany) at the presentation of patients with immunologic reactions and approximately two hours thereafter. The median test was used to compare the extent of ML between individuals who were still symptomatic at follow-up and those who were asymptomatic. (3) Results: We pro-spectively enrolled 16 individuals (10 (63%) female, mean age 50±14 years). Of these, 6 (38%) were still symptomatic at follow-up. Patients who had persistent symptoms had significantly higher ML than those who were asymptomatic (14% (IQR 12-17) vs. 8% (IQR 4-10), p=0.002). (4) Conclusions: ML is elevated in patients who are still symptomatic two hours after presenting to the emergency department due to an immunologic reaction.

One of the main challenges of cultured meat is reducing the costs of production, often described as scaling. The main components of the cultivation process include: cells, media, scaffolds and bioreactors. This work presents an alternative to current stainless steel or glass bioreactors and uses food-grade plant-based scaffolds. Bioreactors must be sterile and leak-free to maintain a proper environment for cell growth. Thermoplastic films are a popular material for constructing these fluidic systems, but traditional methods of welding these film are expensive and do not allow rapid prototyping resulting in high research and development costs for companies. In this study, a laser welding method was developed to join thermoplastic films in a way that prevents contamination and leaks, affording effective macro-fluidics fabrication. This technique was tested using polyethylene (PET) films and a laser cutter operating with settings calibrated for the material to be welded or cut. The laser welding method was found to produce strong, leak-free seals in PET films with minimal heat-induced damage to the films. The ability to design fluidics, chambers and ports of various size. Using this method afforded the incorporation of plant-based scaffolds from food-grade plants (Rice). The laser welding method developed in this study provides a reliable, contamination-free method for the rapid fabrication of fluidic systems for cell cultivation. This technique has the potential to be compatible with a vast range of cell types and scaffolds and to be widely adopted in tissue engineering for regenerative medicine and food applications such as cultured meat.

Abstract: Lipodystrophies (LDs) are rare, complex disorders of the adipose tissue characterized by selective fat loss, altered adipokines profile and metabolic impairment. Sirtuins (SIRTs) are class III NAD+-dependent histone-deacetylases linked to fat metabolism. SIRT1 plays a critical role in metabolic health by deacetylating target proteins in tissues including liver, muscle and adipose tissue. Circulating SIRT1 levels have been found to be reduced in obesity while increased in anorexia nervosa and in patients experiencing weight loss. We evaluated circulating SIRT1 levels in relation to fat amount in 32 lipodystrophic patients affected by congenital or acquired LDs compared to non-LD subjects (24 with anorexia nervosa, 22 normal weight and 24 with obe-sity). SIRT1 serum levels were higher in LDs as compared with normal weight subjects (mean ± SEM: 4.17 ± 0.48 vs. 2.59 ± 0.20 ng/mL) or subjects with obesity (1.7 ± 0.39 ng/mL), whereas they were close to those measured in anorexia nervosa (3.44 ± 0.46 ng/mL). Our findings show that within the LD group there was no relationship between SIRT1 levels and the amount of body fat. The mechanisms responsible for secretion and regulation of SIRT1 in LD deserve further investi-gation.

The development of biomaterial as substitution to connective tissue graft for treating gingival recession is growing nowadays. Hydrogels received attention as potential scaffold to be used in gingival tissue engineering since their capability to mimic soft tissue characteristic as they can hold amount of water. Gelatin is a natural polymer that widely used in hydrogel preparation with good biological properties, but it has poor physical stability for the used as scaffold. Chemical crosslinking strategy using EDC/NHS was performed in this study to overcome its limitation. One uncrosslinked gelatin and two crosslinked gelatin hydrogels different concentration of EDC/NHS were prepared in this study. This study investigated the difference of physical characterization from the prepared gelatin hydrogels. Our findings suggest the crosslinking strategy using EDC/NHS increase physical properties of the gelatin hydrogels without interfering the chemical structure of the gelatin. The higher crosslinker concentration will result in better morphology and more resilient to biodegradation. As a result, the crosslinked gelatin hydrogel with gelatin:EDC:NHS mass ratio of 12:1:1 met the physical characteristic for future use as scaffold for gingival tissue regeneration.

We previously showed that feeding mice a diet containing 1% mantle tissue decreased food consumption, leading to death. We also isolated and identified toxic substances in the mantle tissue. In the present study, we investigated the characteristics and stability of mantle tissue toxicity. Treatment of mantle tissue with 1 mM HCl, 1 mM NaOH, 1 mM dithiothreitol, and 1 mM H2O2 and heating did not reduce the toxicity of mantle tissue in mice. These results suggest that mantle toxins are stable in tissues, particularly when exposed to acidic and digestive enzymes. We examined whether mantle tissue exhibited acute toxicity. Diets containing 1% and 20% mantle extract showed similar levels of toxicity, demonstrating that feeding of mantle tissue does not lead to acute toxicity. Finally, we examined the toxicity of the mantle tissue against small intestinal tissue. Chronic feeding of mantle tissue to mice changed the color of the small intestine. Real-time PCR analysis showed that mantle tissue feeding caused changes of inflammation and endoplasmic reticulum stress markers in the small intestine. These results suggest that feeding of mantle tissue causes toxicity after causing initial damage to the small intestinal tissue.

Background: The incidence of prostate cancer (PC) has been risen annually. Despite the diagnosis is made mainly with non-metastatic PC, mortality is explained by the metastatic disease (mPC). Without a doubt there is an intermediate scenario in which patients have no mPC but will have initiated a metastatic cascade through an epithelial-mesenchymal transition. There is indeed a need for more and better tools to predict what patients will progress in the future to non-localized clinical disease or already have micrometastatic disease, and therefore, will clinically progress after primary treatment. Biomarkers for predicting mPC are still under development; there are few studies and not much evidence of their usefulness. Summary: This review is focused on tissue-based genomic biomarkers (TBGB) for predicting metastatic disease. We developed four main research questions that will attempt to answer according to the current evidence. Why is important to predict metastatic disease? Which tests are available to predict metastatic disease? What impact should there be on clinical guidelines and clinical practice in predicting metastatic disease? What are current prostate cancer treatments? Key Messages: Knowing useful predict tools could help determine which patients may need multimodal or adjuvant treatment even with a localized disease, and in consequence, what patients do not need more than a single modality of treatment. The importance of predicting metastasis is fundamental, given that once metastasis is diagnosed, the quality of life (QoL) and survival drop dramatically.

The role of mesenchymal-to-endothelial transition in the angiogenic response is controversial. Toward this, the present study aimed to determine if fibroblasts contribute to angiogenesis. Endothelial differentiation of fibroblasts was induced by culturing MRC-5 cells (human fetal lung fibroblast cells) on top of Matrigel hydrogel or embedded inside the hydrogel. The formation of ca-pillary-like networks in response to angiogenic signals was observed. The tube formation occurs quickly and can be visualized us-ing a phase-contrast inverted microscope, and/or the cells can be treated with DAPI before the assay and tubes can be visualized through fluorescence or confocal microscopy. Furthermore, fibroblasts cultured in a higher concentration invaded the Matrigel hydrogel and formed stem-cell-like spheroids. These spheroids embedded in matrigel matrices of varying densities sprouted to form 3D connective-tissue networks. Collectively, our results highlight the endothelial differentiation capacity of human lung fibroblasts. The results obtained in this work may have an impact on the search for alternative cell sources for vascular tissue engineering and the overcome of obstacles to vascularization of autologous tissue-engineered constructs and the production of functional grafts for clinical use.

Lack of reliable information on PTC industry in Sri Lanka is hampering the advancement of the technology. Hence, this study attempted to assess the current status of PTC industry in Sri Lanka in order to ascertain the type and the level of interventions needed to broaden the horizons of the industry. Data of last 05 years were collected through qualitative research methods including a questionnaire-based survey, personal interviews, etc. and personal interviews to identify product diversity, R&D, available facilities, production capacity, and markets. Information was analyzed qualitatively using descriptive statistical software to assess the current status, and identify gaps, challenges and opportunities. COVID pandemic and the economic crisis had a heavy toll on the PTC industry. Six major challenges experienced by business owners were identified as increasing capacity, opportunities to build market linkages, demand fluctuations, issues relating to awareness and insufficient support given by the government. Proper identification and screening of mother plants, determining the production capacities and marketing, knowledgeable and skilled human resources, were identified as important contributory factors for success. Development strategies identified mainly include instinctive decision making and government support. Embracing the significant trade achievements through resource reallocation, prioritization and improvisation processes at individual, family group, inter-organizational levels and across these levels need to be regulated through a responsible authority. These interpretations and recommendations of this research can be utilized both by the policy makers and public and private sector organizations for decision making purposes targeting commercial scale advancements.

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs, and able to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials: they exhibit good features in terms of impermeability, deformability and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration: however, this kind of materials lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these mate-rials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields: in the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance and patency will be herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance will be been disclosed.

The choice of parameters for laser beams used in the treatment of musculoskeletal diseases is of great importance. First, to reach high penetration depths into biological tissue and, secondly, to achieve the required effects on a molecular level. The penetration depth depends on the wavelength since there are multiple light-absorbing and scattering molecules in tissue with different absorption spectra. The present study is the first comparing the penetration depth of 1064 nm laser light with light of a smaller wavelength (905 nm) using high-fidelity laser measurement technology. Penetration depths in two types of tissue (porcine skin and bovine muscle) were investigated. The transmittance of 1064 nm light through both tissue types was consistently higher than of 905 nm light. The largest differences (up to 5.9%) were seen in the upper 10 mm of tissue, while the difference vanished with increasing tissue thickness. The higher penetration was most likely due to a combination of lower absorption in hemoglobin and less scattering at larger wavelengths, and not due to absorption in melanin. Overall, differences in penetration depth were comparably small and high peak power and short pulse lengths of laser light seem to be more important to efficiently treat deep musculoskeletal diseases.

Physical activity is well-established as an important protective factor against degenerative conditions and a promoter of tissue growth and renewal. The discovery of FNDC5 as the precursor of irisin in 2012 sparked significant interest in its potential as a diagnostic biomarker and a therapeutic agent for various diseases. Clinical studies have examined the correlation between plasma irisin levels and pathological conditions using a range of assays, but the lack of reliable measurements for endogenous irisin has led to uncertainty about its prognostic/diagnostic potential as an exercise surrogate. Animal and tissue-engineering models have shown the protective effects of irisin treatment in reversing functional impairment and potentially permanent damage, but dosage ambiguities remain unresolved. This review provides a comprehensive examination of the clinical and basic studies of irisin in the context of degenerative conditions and explores its potential as a therapeutic approach in the physiological processes involved in tissue repair/regeneration.

Laser patterning of implant materials for bone tissue engineering purposes has shown to be a promising technique to control cell properties such as adhesion or differentiation, resulting in an enhanced osteointegration. However, the perspective of patterning the bone tissue side interface to generate microstructure effects has never been investigated. In the present study, three different laser-generated patterns were machined on the bone surface with the aim to identify the best surface morphology compatible with osteogenic-related cells recolonization. The laser patterned bone tissue was characterized by electron scanning microscopy and confocal microscopy in order to obtain a comprehensive picture of the bone surface morphology. Cortical bone patterning impact upon cell compatibility and cytoskeleton rearrangement to the patterned surfaces was performed with Stromal Cells from Apical Papilla (SCAPs). Results indicated that laser machining had no detrimental effect upon consecutively seeded cells metabolism. Orientation assays revealed that surface patterning characterized by larger hatch distances was correlated with a higher cell cytoskeletal conformation to the laser-machined patterns. For the first time, to our knowledge, bone is considered and assessed here as a potentially engineered-improvable biological interface. Further studies shall focus on in vivo implications of this direct patterning.

One in four adults in the US suffer from cartilage degeneration of the Intervertebral Disc (DDD) or load bearing joints (DJD). Combined DDD and DJD leads to billions of dollars in surgical health care costs annually. Since cartilage is avascular, it has a limited regenerative capacity. Conventional non-surgical treatment modalities provide brief symptomatic relief, have sided effects, and do not address the actual structural tissue defect in the cartilage itself. As such, new alternatives are needed. Perinatal tissue allografts have emerged as a novel frontier for bio-mechanical cartilage engineering research. Birth product-specific therapeutic roles and clinical outcomes are actively being investigated. The tissues of interest include umbilical cord-derived Wharton’s Jelly (WJ). This study assessed WJ tissue samples via ZEISS Supra 55VP Field-Emission Scanning Electron Microscope (SEM) at 100 and 300nm resolution scales. The captured images of pre and post-processed structural tissue matrices in WJ allografts were analyzed against themselves and peer-reviewed SEM images of articular cartilage, intervertebral disc cartilage, and muscle fascia. SEM images of post-processed WJ structural tissue matrices were analogous to structural tissue matrices in human articular cartilage, intervertebral disc cartilage, and muscle fascia. Relevant characteristics of pre- and post-processed structural tissue matrices in WJ allografts were comparable. This is the first study, that we are aware of, to utilize SEM to compare the pre-and post-processing relevant structural characteristics of WJ allografts and additionally demonstrate that structural collagen matrices in post-processed WJ allografts are analogous in structure to the cartilage in articular joints, intervertebral discs, and muscle fascia.

The natural hosts regarding Orthohantaviruses are rodents, soricomorphs and bats, and it is well known they may cause serious or even fatal diseases among humans worldwide. The virus is persistent among animals and it is shed via urine, saliva and feces, throughout the entirety of their lives. We aim to identify the effectiveness regarding hantavirus detection from rodent tissue samples and urine originating from naturally infected rodents. Initially, animals were trapped at five distinct locations throughout the Transdanubian region in Hungary. Lung, liver, kidney and urine samples were obtained from 163 perished animals. All organs and urine were tested using nested reverse transcriptase-polymerase chain reaction (nRT-PCR). Furthermore, sera were examined for IgG antibodies against DOBV and PUUV viruses by Western Blot assay. IgG antibodies against hantaviruses and/or nucleic acid were detected in 25 (15.3%) cases. Among Apodemus, Myodes, and Microtus rodent species, DOBV, PUUV, TULV were all clearly identified. The virus nucleic acid was detected most effectively from the kidney (100%), while only 55% of screened lung tissues were positive. Interestingly, only 3 out of 20 rodent urine samples were positive regarding nRT-PCR. Moreover, five rodents were seropositive without detectable virus nucleic acid from any of the tested organs.

Glaucoma is a blinding disease largely caused by increased resistance to drainage of fluid from the eye’s anterior chamber, resulting in elevated intraocular pressure (IOP). A major site of fluid outflow regulation and pathology is the trabecular meshwork (TM) at the entrance of the eye’s drainage system. We aimed to characterize the structural and functional properties of a newly developed tissue-engineered anterior segment eye culture model. We hypothesized that repopulation of a decellularized TM with non-native TM cells could restore aspects of normal TM. The decellularization protocol removed all cells and debris while preserving the ECM. Seeded cells localized to the TM region and progressively infiltrated the meshwork ECM. Cells reached a distribution comparable to control TM after four days of perfusion culture. After a perfusion rate increase challenge, tissue-engineered cultures reestablished normal IOPs (reseeded = 13.7±0.4 mmHg, decellularized = 35.2±2.2 mmHg, p < 0.0001). eGFP expressing CrFK control cells caused a high and unstable IOP (27.0±6.2 mmHg). In conclusion, we describe a readily available, storable, and biocompatible scaffold for anterior segment perfusion culture of non-native cells. Tissue-engineered organs demonstrated similarities to native tissues and may reduce the need for scarce donor globes in outflow research.

The cell’s capacity to integrate and respond to spatial information is a crucial feature of morphogenesis and development. The Planar Cell Polarity (PCP) pathway is a signaling mechanism, widely conserved across metazoans, providing spatial orientation along the plane of an epithelium in morphogenic processes ranging from insect wing patterning to mammalian cochleae. Although the core genes involved in the PCP pathway have been molecularly identified in the 1990s, the PCP signaling mechanism remains controversial. In this article I discuss the main players and previous models of PCP signaling reported in the literature, and propose a new model. According to it PCP is established through an homophobic signal by transmembrane protein Frizzled (Fz): 1) a Fz signal in one cell repeals Fz itself in the adjacent cell, thereby generating symmetry breaking; 2) the instructive PCP signal is conveyed through Fz interaction with atypical cadherin Flamingo (Fmi). More broadly, homophobic signaling may represent a novel mechanism for cell-cell signaling of spatial information through modulation of cell adhesion rather than canonical ligand-receptor binding.

Organ-on-Chip is a game-changing technology born from the convergence of tissue engineering and microfluidic technology. Organ-on-Chip devices (OoCs) are expected to offer effective solutions to persisting problems in drug development and personalized disease treatments. This opinion paper surveys the current landscape in research, development, application and market opportunities for OoCs to help establishing a global and multi-stakeholder OoC ecosystem. Based on a bibliometric study, a market analysis, expert interviews, and panel discussions held at the ORCHID Vision Workshop (Stuttgart, 23 May 2018), we outline presently unmet needs, key challenges, barriers and perspectives of the field, and finally propose recommendations towards the definition of a comprehensive roadmap that could render OoCs realistic models of human (patho)physiology in the near future.

This study aimed to investigate Coll-I, III, IV and elastin in canine normal prostate and PC, using Picrosirius red (PSR) and Immunohistochemical (IHC) analysis. Eight normal prostates and 10 PC from formalin-fixed, paraffin-embedded samples were used. Collagen fibers area was analyzed with ImageJ software. The distribution of Coll-I and Coll-III was approximately 80% around prostatic ducts and acini, 15% among smooth muscle and 5% surrounding blood vessels, in both normal prostate and PC. There was a higher median area of Coll-III in PC, when compared to normal prostatic tissue (p=0.001 for PSR and p= 0.05 for IHC). Immunostaining for Coll-IV was observed in the basal membrane of prostate acini, smooth muscle, blood vessels, and nerve fibers of normal and PC samples. Although there was no difference in Coll-IV area between normal tissue and PC, tumors with Gleason score 10 showed absence of Coll-IV, when compared to scores 6 and 8 (p=0.0095). Elastic fibers were found in the septa dividing the lobules and around the prostatic acini of normal samples, and was statistically higher in PC, compared to normal tissue (p=0.00229). Investigation of ECM components brings new information and should be correlated with prognosis in future studies.

Obesity, which is characterized by an excessive accumulation of body fat, is one of the critical factors causing metabolic syndrome. Many studies have been performed to identify appropriate agents to control obesity, but toxicity remains a problem. Herein, we identified that phenylbutyrate (PBA), which has been used to treat urea cycle disorder with very low toxicity for a long time, efficiently inhibited high fat-induced body weight gain in a diet-induced obesity mouse model (DIO model). PBA treatment decreased body fat mass and increased lean composition. Moreover, PBA increased brown adipose tissue (BAT) activity by increasing glucose uptake, thereby improving glucose tolerance and insulin tolerance. Interestingly, PBA could induce the expression of phosphofructokinase (PFKL), a key enzyme in the glycolytic pathway, and knocking down PFKL dramatically repressed the expression level of Ucp1 as well as those of Prdm16, Cidea, Pgc1α, and Pparγ, which are marker genes for BAT activation. These results strongly suggested that PBA could increase energy expenditure by increasing BAT activity via the induction of PFKL. Taken together, PBA could be used as a therapeutic agent for people with obesity to prevent the development of metabolic syndrome.

The regeneration of bone tissue is a main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, while it should be resorbed even in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated and it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also on osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between the formation of new bone tissue and material degradation has not been found until now. The addition of different substances such as collagen or growth factors and also of different cell types have already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are differently used as basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designated for bone regeneration with the aim to give an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.

The objective of this research was to examine apoptosis status in the laminar tissue of dairy cows with OF-induced laminitis. A total of 12 clinically healthy non-pregnant Holstein cows were randomly allocated into 2 groups of 6 cows each: the control group and the oligofructose treated group (OF group), respectively. At 0 h, 17 g/kg BW of oligofructose dissolved in 20 mL/kg BW of warm deionized water were administered to the dairy cows of OF group via a stomach tube, and dairy cows in control group were received with the said volume of deionized water by the same method. At -72 h before and 0 h, 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 60 h, and 72 h after OF overload, clinical examination in both groups were performed. After 72 h, laminar tissues of dairy cows in both groups were taken to determine genes and proteins. We observed that the gene expression of Bax (P&lt;0.01), and P53 (P&lt;0.05) significantly up-regulated, whereas that of Bcl2 significantly down-regulated (P&lt;0.01) in the afflicted cows compared to the control cows. The protein expression of Bax (P&lt;0.01), Bif1 (P&lt;0.01), caspase3 (P&lt;0.01), caspase8 (P&lt;0.05), and caspase9/9p (P&lt;0.05) significantly up-regulated, while that of Bcl2 significantly downregulated (P&lt;0.01) in the afflicted cows compared to the control cows. Moreover, the distribution of Bax (P&lt;0.01) and P53 (P&lt;0.01) proteins in laminar tissue significantly up-regulated (P&lt;0.01) in the sick cows compared with the control cows. These results suggested that unregulated genes and proteins status of apoptosis-associated indicators may be a typical cause for epidermal attachment failure which serves a key role in the pathogenesis of dairy cow laminitis. Nevertheless, further large-scale gene and protein-level studies are required to fully explain the pathogenesis of laminitis in dairy cows.

Flap surgery is a common method used to cover defects following tumor ablation, trauma, or infection. However, insufficient vascularity in the transferred flap can lead to flap necrosis and failure. Proper postoperative monitoring is essential to prevent these complications. Recently, research has explored the use of infrared thermal imaging in plastic surgery, leading to its clinical application. This study investigates the use of a forward-looking infrared (FLIR) camera to monitor blood flow in flaps. In the study, 28 rats underwent reverse McFarlane flap surgery, and their flaps were analyzed using a FLIR thermal imaging camera seven days post-surgery. Additionally, thermal images of flaps were taken on postoperative days 0, 1, 2, 3, and 7 in 22 patients. The study focused on temperature differences between normal skin and the perforator compared to the average flap temperature. Results showed that the temperature difference was higher in the necrosis group and increased over time in cases of total necrosis. A lower perforator temperature compared to the flap's average indicated vascular compromise, potentially leading to flap failure. The FLIR camera, being contact-free and convenient, shows promise for understanding and inferring the clinical progression of flaps in postoperative monitoring.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Plants can utilize the different forms of nitrogen (N), including inorganic and organic N nutrients, and show the great difference in the utilizing efficiency of N-form among species and genotypes within a species. In our previous study, we found that Tibetan wild barley (XZ16) was better in utilization of organic nitrogen in comparison with cultivated barley (Hua30). In this study, metabolite profiles of the two barley genotypes were comprehensively compared in their response to four N forms, including nitrate (NO3-), ammonium (NH4+), urea and glycine. Macro-and micro-nutrient concentrations in shoots were mostly found higher in nitrate and urea treatments than in ammonium and glycine in both the genotypes. XZ16 had higher concentrations of nutrient ions in glycine treatment, but Hua30 accumulated more nutrients in ammonium treatment. Among the total 163 differentially expressed metabolites, highest up-regulation and highest down-regulation was found in XZ16 in glycine and urea treatments respectively. Some important metabolites such as proline, glutamine, serine, asparagine, L-homoserine, aspartic acid, putrescine, ornithine, 4-aminobutyrate were up-regulated in glycine treatment in both the genotypes with higher fold change in XZ16 than in Hua30. Similarly, fructose-6-PO4, aconitic acid and isocitrate were only up-regulated in XZ16 in glycine treatment. Here, we concluded that the genotype XZ16 exhibited higher response to glycine treatment, while Hua30 showed higher response to NH4+ treatment which is attributed to their better utilization of glycine-N and NH4+-N, respectively. .

African Swine Fever (ASF) poses a significant threat to domestic pig populations worldwide. This study investigates the histopathological alterations in confirmed ASF-positive domestic pigs, focusing on over 100 cases from 2018 to 2021. Biological material from 118 pigs, confirmed ASF-positive via PCR examination, was histopathologically examined. Tissue samples from various organs were processed, embedded, and analyzed using hematoxylin and eosin staining. Immunohistochemistry (IHC) was employed to detect the major capsid protein (p72) of the ASF virus.Histological examination revealed characteristic ASF lesions, including severe hemorrhages, lymphoid depletion, and inflammatory infiltrates. Vascular anomalies leading to hemorrhagic events were widespread. Microthromboses were prevalent in lymph nodes and kidneys. IHC detected p72 in various organs, with tonsils consistently showing the highest viral presence.This comprehensive study underscores the pivotal role of lymph nodes, spleen, and kidneys in ASF pathogenesis, highlighting prominent vascular involvement and hemorrhagic manifestations. The study establishes the efficacy of IHC in detecting ASF virus, even in autolyzed tissue samples. Tonsils emerge as a consistent epicenter of viral presence, shedding light on the intricate pathogenesis of ASFV.

Nanotechnology has become an increasingly promising medical field, particularly scar removal. Scar removal is a complex process involving regenerating damaged skin tissue, and nanotechnology presents unique solutions to this issue. One potential application of nanotechnology is using nanofibers as scaffolds to support the growth of new skin tissue. These fibres can also be loaded with drugs or growth factors to promote tissue regeneration and reduce scarring. Another potential application is nanocarriers for drug delivery to specific body areas, which can promote tissue regeneration and reduce scarring.Additionally, nanotechnology has been utilized to create new materials for skin regeneration, such as "nano skin" that mimics the structure of natural skin. Nanoprobes have also been developed for the detection of scar tissue and the monitoring of its progression. These potential nanotechnology applications offer exciting possibilities for the future of scar removal and skin repair. With further research and development, nanotechnology has the potential to revolutionize scar removal and provide more effective solutions for tissue regeneration.

Demethyleneberberine is an active component extracted from the Chinese herbal drug Cortex Phellodendri. It is also a metabolite of the berberine in animals and humans. However, the pharmacokinetics, tissue distribution and excretion of demethyleneberberine have not been reported. The present study aimed to investigate the pharmacokinetic parameters of demethyleneberberine by developing a method of high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The detection was performed by using positive ion electrospray ionization in multiple reaction monitoring mode. The MS/MS ion transitions were monitored at m/z 324.4→308.3 for demethyleneberberine and 465.5→350.3 for IS. After oral administration of demethyleneberberine in rats and mice, the pharmacokinetics, tissue distribution, and excretion of desmethylberberine in rats and mice were comparatively studied for the first time. The plasma concentration of desmethylberberine reached its peak within 5 min after oral administration in both rats and mice. The bioavailability of rats and mice was comparable, ranging from 4.47% to 5.94%, higher than that of berberine. The total excretion of desmethylberberine in urine, feces and bile is 7.28~9.77%. These findings provide valuable insights into the pharmacological and clinical research on desmethylberberine.

De novo regeneration of Cannabis sativa L. (cannabis) using tissue culture techniques remains unreliable and infrequent. Conventional methods for the regeneration and transformation of cannabis have not achieved the reliability and replicability needed to be integrated into research and breeding programs. Protoplast systems are effective for gene expression studies, transformation and genome editing technologies, and opens the possibility of somatic hybridization to create interspecific hybrids. To date, leaf-derived protoplast have been isolated for transient gene expression studies, but attempts at protoplast-to-plant regeneration have not been reported. The present study aims to test the efficacy of using a callus culture system, as an abundant source for protoplast isolation and lays the groundwork for a protoplast-to-plant regeneration system. Using hypocotyl-derived callus cultures, which are known to have relatively greater regenerative potential, the efficacy of protoplast isolation and initial cell division were assessed. In this study, the effect of 2-aminoindane-2-phosphonic acid (AIP) in callus culture media and the effect of subculture frequency on protoplast yield were assessed. This study found that inclusion of AIP at 1 mM resulted in a 334% increase in protoplast yield compared with AIP-free medium, representing the first known use of AIP in cannabis tissue culture. Inclusion of AIP led to a 28% decrease in total soluble phenolics and 52% decrease in tissue browning compared to the control medium. Lastly, a two-phase culture system for protoplast regeneration was tested. At a concentration of 2.0×10^5 protoplasts per mL, division was observed, providing the first know report of cell division from cannabis protoplasts and setting the stage for future development of a protoplast-to-plant regeneration system.

Background: This study aimed to investigate the effect of fascial manipulation (FM) of the deep cervical fascia (DCF) and sequential yoga poses (SYP) on pain and function in individuals with mechanical neck pain (MNP). Method: Following the predefined criteria, ninety-nine individuals with MNP were recruited, randomised and assigned to either the intervention group (IG) (n=51) or the control group (CG) (n=48). Individuals in the IG received FM (4 sessions in 4 weeks) along with the home-based SYP (4 weeks). The CG participants received the usual care (cervical mobilization and thoracic manipulation (4 sessions in 4 weeks) along with unsupervised therapeutic exercises (4 weeks). The participants underwent baseline and weekly follow-up measurements of pain using a numerical pain rating scale (NPRS) and elbow extension range of motion (EEROM) during upper limb neurodynamic test 1 (ULNT1). The baseline and the 4th session follow-up measurements of the Patient-specific Functional Scale (PSFS) and Fear-avoidance Behavior Questionnaire (FABQ) were also taken. Results: A repeated-measures ANOVA was performed. The mean differences between the IG and CG on NPRS 3rd and 4th sessions are -1.009 (p&lt; 0.05) and -1.701 (p&lt; 0.001), respectively; on EEROM in the 4th session is 20.120 (p&lt; 0.001); on FABQ during the follow-up is -5.036 (p&lt;0.001), showing a statistically significant difference, whereas on PSFS during follow-up is 0.263 (p=0.566), suggesting no significant differences in PSFS. Conclusion: FM and SYP can aid in reducing pain and fear avoidance behavior as well as improving the function and extensibility of the upper quarter region.

Exosomes are membrane-bound, biologically active nanovesicles of size 30-200 nm produced by many cell types, such as both mammalian and plant cells. They are wrapped in a phospholipid bilayer and play a significant role in intercellular communications. The ease in their isolation and the ability of plant-derived exosome-like nanovesicles (PDEVs) to efficiently deliver bioactive constituents into mammalian cells have made them popular in contemporary research. PDEVs share many characteristics with mammalian EVs (MEVs), including shape, size, surface charge, and consist of bioactive molecules like lipids, proteins, nucleic acids, and tiny metabolites. However, the chemical composition profile of PDEVs and their biogenesis mechanism differ significantly from those of MEVs. They have been widely explored as potential therapeutic agents and are considered as good alternatives to act as a carrier for drug delivery. The present work elucidates the isolation of exosome-like-nanovesicles (henceforth exosomes) from the culture supernatants of an in vitro cultured callus tissue derived from a bone healing plant known for its osteogenic activity, i.e., Cissus quadrangularis. The physical and biological properties of exosomes were successfully studied using different characterization techniques. To assess their therapeutic potential, we studied the internalisation of calcein-AM labeled exosomes by human derived mesenchymal stromal cells (hMSCs). Additionally, we evaluated the potential of exosomes in the migration of cells in a cell scratch assay with hMSCs and their effect on amelioration of oxidative stress was investigated on preosteoblast MC3T3-E1 cells that were pre-treated with these exosomes. Furthermore, we investigated their proliferation and differentiation to osteoblasts like cells with the help of resazurin assay and alkaline phosphatase assay (ALP). The obtained results provide a primary justification for the use of Cissus quadrangularis-derived exosomes as a nanocarrier for drug molecules for various therapeutic bone applications.

Mesenchymal stem cells (MSCs) are an attractive therapeutic tool for tissue engineering and regenerative medicine owing to their regenerative and trophic properties. The best-known and most widely used are bone marrow MSCs which are currently being harvested and developed from a wide range of adult and perinatal tissues. MSCs from different sources are believed to have different secretion potentials and production which may influence their therapeutic effects. To confirm it, we performed a quantitative proteomic analysis based on the TMT technique of MSCs from three different sources: Wharton’s jelly (WJ), dental pulp (DP) and bone marrow (BM). Our analysis focused on MSC biological properties of interest for tissue engineering. We identified a total of 611 differentially expressed human proteins. WJ-MSCs showed the greatest variation compared with the other sources. WJ produced more extracellular matrix (ECM) proteins and ECM-affiliated proteins and appeared more able to modulate the inflammatory and immune response. BM-MSCs displayed enhanced differentiation and paracrine communication capabilities. DP-MSC appeared to promote exosome production. The results obtained confirm the existence of differences between WJ, DP and BM-MSC and the need to select the MSC origin according to the therapeutic objective sought.

Salinity is the most significant abiotic stress affecting crop yield worldwide, breeders are Salinity is the most important abiotic stress limiting crop production throughout the world, and breeders are encouraged to test novel genotypes for their resistance to this selection agent. However, getting a sufficient number of plants for the evaluation can be a lengthy and time-consuming procedure that might be shortened by applying in vitro techniques. An experiment was conducted under controlled saline circumstances using a tissue culture technique to investigate the influence of salt on several physic-biochemical parameters. Micro-shoots of Volkamariana lemon, sour orange, trifoliate orange, and Cleopatra mandarin rootstocks were re-cultured on MS media supplemented with NaCl from 25, up to 150 mM. Following the experiments, all of the tested rootstocks' morphological and biochemical characteristics, stomata behavior, and element accumulation were measured. As a result, adding NaCl from 25 to 150 mM to MS media caused a reduction in all morphogenetic parameters such as shoot number, shoot length, leaves number, and survival percentage was measured compared with control. Photosynthesis pigment, RWC, K, and Ca ions were decreased by increasing NaCl from 100 to 150 mM. On the contrary, proline, Cl, and Na were increased. Cleopatra mandarin and Trifoliate orange are more tolerant to salt stress than Volkamariana lemon and sour orange citrus.

In this study, 3D printing of poly-l-lactic acid (PLLA) scaffolds reinforced with graphene oxide (GO) nanoparticles via Digital Light Processing (DLP) was investigated to mimic bone tissue. Stereolithography is one of the most accurate additive manufacturing method, but the dominant available materials used in this method are toxic. In this research, a biocompatible resin (PLLA) was synthetized and functionalized to serve the purpose. Due to the low mechanical properties of the printed product with the neat resin, graphene oxide nanoparticles in three levels (0.5, 1, and 1.5 Wt.%) were added with the aim of enhancing the mechanical properties. At first, the optimum post cure time of the neat resin was investigated. Consequently, all the parts were post-cured for three hours after printing. Due to the temperature-dependent structure of GO, all samples were placed in an oven at 85 ° C for different time periods of 0, 6, 12, and 18 hours to increase mechanical properties. The compression test of heat treated samples reveals that the compressive strength of the printed parts containing 0.5,1, and 1.5 % of GO increased by 151,162 ad 235%, respectively. Scaffolds with the designed pore sizes of 750 microns and a porosity of 40% were printed. Surface hydrophilicity test was performed for all samples showing that the hydrophilicity of the samples increased with increasing GO percentage. The degradation behavior of the samples was evaluated in a PBS environment, and it revealed that by increasing GO, the rate of component degradation increased, but the heat treatment had the opposite effect and decreased the degradation rate. Finally, besides improving biological properties, a significant increase in mechanical properties under compression can introduce the printed scaffolds as a suitable option for bone implants.

Laminitis is considered as an important underlying cause of lameness diseases, yet its specific pathogenesis remains unclear. Autophagy is an intracellular degradation mechanism that controls recycling of membrane-associated integrin and may aid in the progression of metabolic diseases. But the significance of autophagy for initiation and development of laminitis is unknown. The present study aimed to explore autophagy activity in the laminar tissue of dairy cows with oligofructose-induced laminitis. Twelve healthy non-pregnant Holstein cows were randomly divided to 2 groups of 6 cows each, entitled the control group and the oligofructose overload group (OF group), respectively. At 0 h, cows in OF group were gavaged with oligofructose (17 g/kg BW) dissolved in warm deionized water (20 mL/kg BW) through oral rumen tube, and dairy cows in control group were gavaged with the same volume of deionized water by the same method. At -72 h before perfusion as well as 0 h, 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 60 h, and 72 h after perfusion, clinical evaluations in both groups were monitored. After 72 h, laminar tissues of dairy cows in both groups were collected to examine genes and proteins. We found the significantly higher (P<0.05) levels of mRNA ATG5, ATG12, and Becilin1, but P62 and mTOR were extensively lower (P<0.01) in the laminar tissue of the OF group than the control group. Protein expression level of Becilin-1 was higher significantly (P<0.05), and the protein expression level of LC3II was lower significantly (P<0.05) in OF group than control group. However, the expression of P62 reduced (P>0.05) non-significantly in OF group than control group. The distribution of Beclin1 protein in laminar tissue increased (P<0.01) significantly, and distribution of P62 protein decreased (P<0.05) significantly in OF group than control group. In conclusion, laminar tissue damage occurred during the onset of laminitis, which promoted the occurrence of autophagy, and confirmed that autophagy was involved in the regulation and pathogenesis of laminitis in dairy cows.

Accidental soft tissue injuries are a frequent injury. We report a case involving a 37-year-old man with a soft tissue wound failing conservative treatment. The use of applied fibrin membranes and concentrated growth factors yielded a resolution of the injury in 16 months without need of skin grafting.

Adiposity is associated with adverse health conditions such as obesity, cardiovascular disease and type 2 diabetes. The combination of resistance exercise and creatine supplementation has been shown to decrease body fat % in adults ≥ 50 years of age. However, the effects in adults < 50 years of age is unknown. To address this limitation, we systematically reviewed the literature and performed several meta-analyses comparing studies that included resistance exercise and creatine supplementation to resistance exercise and placebo. Twelve studies were included involving 266 participants. Adults (< 50 years of age) that supplemented with creatine and performed resistance exercise experienced a significant reduction in body fat % (-1.19%, p=0.006) and a non-significant reduction in absolute fat mass (-0.09 kg, p=0.88). Collectively, the combination of resistance exercise and creatine supplementation produces a very small reduction in body fat % in adults < 50 years of age.

Adipose tissue composition contributes greatly to the quality and nutritional value of meat. Transcriptomic and lipidomic techniques were used to investigate the molecular mechanism of fat deposition difference among Ningxiang, Berkshire and F1 pigs. Transcriptomic analysis identified 680, 592 and 380 differentially expressed genes (DEGs) by comparing the groups of Ningxiang pigs vs Berkshire pigs, Berkshire pigs vs F1 pigs, Ningxiang pigs vs F1 pigs. Lipidomic analysis screened 423, 252, and 50 significantly changed lipids (SCLs) by comparing the groups of Ningxiang pigs vs Berkshire pigs, Berkshire pigs vs F1 pigs, Ningxiang pigs vs F1 pigs. Lycine, serine and threonine metabolism pathway, fatty acid biosynthesis and metabolism related pathways were siginificant enriched in the groups of Berkshire pigs vs Ningxiang pigs and Berkshire pigs vs F1 pigs. The DEGs (PHGDH, LOC110256000) and the SCLs (Phosphatidylserines) may have a great impact on lycine, serine and threonine metabolism pathway. Moreover, the DEGs (FASN, ACACA, CBR4, SCD, ELOV6, HACD, CYP3A46, CYP2B22, GPX1, GPX3) and the SCLs (palmitoleic acid, linoleic acid, arachidonic acid, icosadienoic acid) play important role in fatty acid biosynthesis and metabolism. Thus, the fat deposition difference among Ningxiang, Berkshire and F1 pigs may be caused by the difference of the expression pattern of key genes in multiple enrichment KEGG pathways. The research presented multiple lipids that were potentially available biological indicator and screened key genes that were potentially gene targets for molecular design breeding. The research also explored the molecular mechanisms of fat deposition difference among Ningxiang, Berkshire and F1 pigs and provides insight into the selection of backfat thickness and fat composition of adipose tissue for future breeding strategies.

This work aims to investigate the expression levels of four preselected miRNAs previously linked to Cancer and/or Obesity, with the purpose of finding potential biomarkers in the clinical management of Colorectal Cancer (CRC) developed by obese and non-obese patients. We analyzed samples from a total of 65 subjects, 43 affected by CRC and 22 without cancer. Serum and both subcutaneous and omental adipose tissues (SAT and OAT) were analyzed, as well as tumor and non-tumor colorectal tissues in the case of the CRC patients. The relative expression (2-∆∆Ct) levels of 4 miRNAs (miR-181a-5p, miR-143-3p, miR-132-3p and miR-23a-3p) were measured by RT-qPCR. Serum, SAT and OAT expression levels of these miRNAs showed significant differences between subjects with and without CRC, especially in the group of overweight/obese subjects. In CRC serum levels of miR-181a-5p, miR-143-3p and miR-23a-3p correlated with their levels in both SAT and OAT. Moreover, in the case of miR-181a-5p, these correlations were significantly influenced by the body mass index (BMI). From these data, we can conclude that both adiposity and CRC induce changes in the expression of the miRNAs investigated, demonstrating the potential utility of this panel of miRNAs in the diagnosis and prognosis of CRC patients.

The injectable hydrated calcium phosphate bone-like paste (hCPP) have been developed with suitable nanoscale characteristics and unindered injection through 23G standard needles. In vitro assays showed the cytocompatibility of hCPP with mesenchymal embryonic C3H10T1/2 cell cultures. The hCPPs were identified to be composed of aggregated nano-sized particles with sphere-like shapes with low crystallinity. The ability of serum proteins (FBS) to adsorb on hCPP particles was also studied. The hCPP demonstrated high protein adsorption capacity, thereby indicating its potential in various biomedical applications. The results of the in vivo assay upon subcutaneous injection in Wistar rats indicated the nontoxicity and biocompatibility of experimental hCPP, as well as the gradual resorption of hCPP, comparable to the period of bone regeneration. The data obtained are of great interest for the development of commercial highly effective osteoplastic materials for bone tissue regeneration and augmentation.

Regeneration of biological tissues in medicine is challenging, and 3D bioprinting offers an innovative way to create functional multicellular tissues. One common way in bioprinting is bioink which is one type of the cell-loaded hydrogel. For clinical application, however, the bioprinting still suffers from satisfactory performance, e.g. in vascularization, effective antibacterial, immunomodulation and regulation of collagen deposition. Many studies have incorporated different bioactive materials into the 3D printed scaffolds to optimize the bioprinting. Here, we review a variety of additives added to the 3D bioprinting hydrogel. The underlying mechanisms and methodology for biological regeneration are important and will provide useful basis for future research.

Background: Chronic Back Pain due to Facet Joint Syndrome is a common and debilitating con-dition. Advances in regenerative medicine have shown that Autologous Unmodified Adipose Tissue-Derived Regenerative Cells (ADRC) provide several beneficial effects [1,2]. These regen-erative cells can differentiate into various tissues [3] and exhibit a strong anti-inflammatory po-tential. ADRCs can be obtained from a small amount of fatty tissue derived from the patient´s abdominal fat. Methods: We report long-term results of 37 patients (age 31-78 years, mean 62.5) suffering from “Facet Joint Syndrome” The pathology was confirmed by clinical, radiological examinations and fluoroscopically guided test injections. Then liposuction was performed. 50-100 cc of fat were harvested. To recover stem cells from adipose tissue, we use the CE-certified Transpose RT™ system from InGeneron GmbH. The cells were then injected under fluoroscopic control in the periarticular fat. Follow-up examinations were performed at one week 1 and 5 years. Results: Every patient reported improved VAS pain at any follow-up (1 week, 1, and 5 years) with ADRCs compared to the baseline. Conclusion: Our observational data indicate that facet joint syndrome patients treated with unmodified adipose tissue-derived regenerative cells experience improved quality of life in the long term.

The genus Musa spp. contains commercially important fleshy fruit producing plants including plantains and bananas with a strong potential of providing food security and source of revenue to farmers. Occasionally, plantlets are often not available to fulfill the supply demand of farmers particularly in Caribbean region. Concerns with the quality of vegetative tissues along with the possibility of the transmission of phytopathogens makes availability of plantlets limited to farm-ers. Micropropagation of plantains offers an alternative to producing large number of in-vitro plantlets. However, conventional methods of micropropagation techniques require high produc-tion costs and are labor-intensive. Recently, Temporary Immersion Bioreactor (TIB) has emerged as an alternative to conventional micropropagation methods. Our work utilized SEM (Scanning Electron Microscope), molecular and biochemical tools (qRT-PCR and ICP-OES) to characterize and compare the morphological, elemental composition, and photosynthetic gene expression of plantains cultured on TIB. Additionally, morphological features of growth and propagation rates were analyzed for comparing outputs obtained from temporary immersion bioreactor with conventional micropropagation (CM) techniques. Results showed higher growth and multiplication rates for plantlets cultivated in TIB. Gene expression analysis of selected photosynthetic genes demonstrated high transcript abundance of phosphoenol pyruvate carboxylase (PEPC) in plantain tissues obtained by TIB. Elemental composition analysis showed higher content of iron in plantains grown in TIB suggesting a potential correlation with PEPC expression. These results demonstrate the potential of TIB to be an efficient method to produce healthy in-vitro plantains.

Molecular diagnostics in healthcare relies increasingly on genomic and transcriptomic method-ologies and requires appropriate tissue specimens from which nucleic acids (NA) of sufficiently high quality can be obtained. Besides suration of ischemia and fixation type, NA quality depends on a variety of other pre-analytical parameters, like storage conditions and duration. It has been discussed that improper dehydration of tissue during processing influences quality of NAs and shelf-life of fixed tissue. Here we report on establishing a method to determine the amount of residual water in fixed, paraffin-embedded tissue (fixed by neutral buffered formalin, or a non-crosslinking fixative) and its correlation to the performance of NAs in qRT-PCR analyses. The amount of residual water depended primarily on the fixative type and the dehydration pro-tocol and, to a lesser extent on storage conditions and time. Moreover, we found that these pa-rameters were associated with the qRT-PCR performance of extracted NAs. Besides cross-linking of NAs and modification of nucleobases by formalin, hydrolysis of NAs by residual water was found to contribute to reduced qRT-PCR performance. The negative effects of residual water on NA stability are not only important for the design and interpretation of research, but must also be taken into account in clinical diagnostics where reanalysis of archived tissue from a primary tumour may be required, e.g., after disease recurrence. We conclude that improving shelf-life of fixed tissue requires meticulous dehydration and dry storage to minimize the degradative in-fluence of residual water on NAs.

The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given the approximately 8,000 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially-available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies compared to in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus have virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.

Orbital fractures are a common finding in facial trauma and serious complications may arise when orbital reconstruction is not done properly. The virtual planning can be used to manufacture patient-specific titanium orbital implants (PSI) through the process of selective laser melting. This method is currently considered the most accurate technique for orbital reconstruction. Even with the most accurate tehniques of bone reconstruction, there are still situations where enophthalmos is present after reconstruction which may be produced by intraorbital soft tissue atrophy. The aim of this paper was to evaluate the orbital soft tissue after postraumatic reconstruction of the orbital walls fractures. 10 patients diagnosed with unilateral orbital fractures were included in this study. A CT scan of the head region with thin slices (0.6mm) and soft and bone tissue windows was done. After data processing, the STL files were exported and the intraorbital fat tissue volume and the muscular tissue volume were masured. The volumes of affected orbit tissues were compared with the volumes of the healthy orbit tissues for each patient. Our findings conclude that a higher or a lower grade of fat and muscular tissue loss is present in all cases of reconstructed orbital fractures.

Abstract : This paper presents the investigation of biomechanical behaviour of sheep heart fibre using uniaxial tests in various samples. Non-linear Finite Element models (FEA) that are utilised in understanding mechanisms of different diseases may not be developed without the accurate material properties. This paper presents uniaxial mechanical testing data of the sheep heart fibre. The mechanical uniaxial data of the heart fibre was then used in fitting four constitutive models including the Fung model, Polynomial (Anisotropic), Holzapfel (2005) model, Holzapfel (2000) model and the Four-fibre Family model. Even though the constitutive models for soft tissues including heart myocardium have been presented over several decades, there is still a need for accurate material parameters from reliable hyperelastic constitutive models. Therefore, the aim of this research paper is to select five hyperelastic constitutive models and fit experimental data in the uniaxial experimental data of the sheep heart fibre. A fitting algorithm was made used to optimally fitting and determination of the material parameters based on selected hyperelastic constitutive model. In this study, the evaluation index (EI) was used to measure the performance and capability of each selected anisotropic hyperelatic model. It was observed that the best predictive capability of the mechanical behaviour of sheep heart fibre the Polynomial (anisotropic) model has the EI of 100 and this means that it is the best performance when compared to all the other models.

Cancer cachexia is a multifactorial syndrome that is identified by ongoing muscle atrophy, along with functional impairment, anorexia, weakness, fatigue, anemia, reduced tolerance to antitumor treatments. Thus, reducing the patients’ quality of life. Cachexia alone causes about 22-25% of cancer deaths. This review covers the symptoms, mediators, available treatment, and prospects of 3D bioprinting for cancer cachexia. Studies about cachexia have shown several factors that drive this disease – protein breakdown, inflammatory cytokines activation, and mitochondrial alteration. Even with proper nutrition, physical exercises, anti-inflammatory agents, chemotherapy, and grafting attempts, standard treatment has been unsuccessful for cachexia. But the use of 3D bioprinting shows much promise compared to conventional methods by attempting to fabricate 3D constructs mimicking the native muscle tissues. In this review, some 3D bioprinting techniques with their advantages and drawbacks, along with their achievements and challenges in in-vivo applications have been discussed. Constructs with neural integration or muscle-tendon units aim to repair muscle atrophy. But it is still difficult to properly bio-print these complex muscles. Although progress can be made by developing new bio-inks or 3D printers to fabricate high-resolution constructs. Using secondary data, this review study shows prospects of why 3D bioprinting can be a good alternate approach to fight cachexia.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

Biological micro-dissection has a wide range of applications in the field of molecular pathology. The current laser-assisted dissection technology is expensive, and laser radiation can lead to sample contamination. As an economical and pollution-free micro-dissection method, piezoelectric ultrasonic micro-dissection has a wide application prospect. However, the performance of the current piezoelectric ultrasonic micro-dissection technology is unsatisfactory. In this paper, a novel piezoelectric ultrasonic micro-dissection device based on a flexure mechanism is proposed in order to solve the problems of low dissecting precision and excessive wear of the dissecting needle caused by the harmful lateral vibration of the current piezoelectric ultrasonic micro-dissection device. By analyzing the flexibility of flexure hinge, the type of flexure beam and the optimal design parameters are determined. Through comparing the harmonic response simulation analysis of the micro-dissection device based on a flexure mechanism and the traditional micro-dissection device without the flexure mechanism, the newly designed micro-dissection device achieves the best vibration effect when the driving frequency is 28kHz, compared with the traditional micro-dissection device, the lateral vibration suppression effect is improved by 68%. Then, based on the 3D printing technology, a prototype of a novel micro-dissection device was produced, and its performance was tested. It was found that the flexure mechanism did indeed suppress the lateral vibration of the needle tip. Finally, the experiments of 5μm thick paraffin-embedded rat liver sections were carried out, and the effects of different dissecting parameters on the dissecting effect were analyzed, and the optimal dissecting parameters were obtained. By comparing the dissecting effects of the tissue sample and the wear condition of the needle tip between the novel micro-dissection device and the traditional micro-dissection device under their optimal dissecting parameters, it is proved that the suppression of harmful lateral vibration not only significantly improves the dissecting effect, but also improves the service life and durability of the dissecting needle, which is beneficial to reduce the equipment costs.

Most commercial Cannabis sativa L. (cannabis) genotypes are short-day plants and cultivators typically use a 12.0 h uninterrupted dark period to induce flowering; however, scientific information is lacking to prove this is the optimal dark period for all genotypes, and cultivar specific photoperiods may increase productivity. Tissue culture can be used for research requiring multiple treatments, proper replication, and in a controlled environment on a smaller scale compared to greenhouse and indoor facilities. To determine whether cannabis explants can flower under varied photoperiods in vitro, explants were grown under one of six photoperiod treatments: 12.0, 13.2, 13.8, 14.4, 15.0, and 16.0 h for four weeks. The percentage of flowering explants was highest under 12.0 and 13.2 h treatments. There were no treatment effects on the fresh weight, final height, or growth index of the explants. The results suggest an uninterrupted dark period of at least 10.8 h (i.e. 13.2 h photoperiod) is needed to induce the flowering of this genotype. In vitro flowering could provide a unique and high throughput approach to study floral/seed development and secondary metabolism in cannabis under highly controlled conditions. Further research should determine if this response is the same on a whole plant level.

Acne vulgaris is a chronic skin disease, which occurs due to inflammation of the hair follicles and sebum producing (sebaceous) glands of the skin called pilosebaceous unit and the anaerobic propionic acne bacterium, P.acne. Human sebum is dominantly made up of 57.5% of triglycerides and fatty acids, 26%wax esters, 12% Squalene and 4.5% Cholesterol. The increased level Androgen hormone, sebum lipid composition, P.acne over growth which induces monocytes and pro inflammatory cytokines attracts neutrophils, basophils, and T cells to the pilosebaceous unit and drive epithelial hyper proliferation i.e., Acne vulgaris. The actual biomolecular changes due to acne vulgaris disease are present in the blood, in the sebum, and in the noninvasive sample of human scalp hair follicles. The main objectives of the present study are to analyze human scalp hair follicles samples using FTIR-ATR spectroscopy to compare and discriminate the spectral signatures of acne vulgaris and healthy scalp hair tissue samples through acne biomarkers Protein, Amide I, Amide II and Squalene (LDL), using the method of internal ratio parameters. This work represents a first step in the development of an analytical tool for future drug development.

Nanomedicine has allowed for emerging advances in imaging, diagnostics and therapeutics. Regenerative Medicine has taken advantage of a number of nanomaterials for reparation of diseased or damaged tissues in the nervous system involved in memory, cognition and movement. Electrical, thermal, mechanical and biocompatibility aspects of carbon-based nanomaterials (nanotubes, graphene, fullerenes and their derivatives) make them suitable candidates to drive nerve tissue repair and stimulation. This review article focuses on recent advances on the use of carbon nanotube (CNT)-based technologies on nerve tissue engineering; outlining how neurons interact with the nanomaterials interface for promoting neuronal differentiation, growth and network reconstruction for their possible use in therapies of neurodegenerative pathologies and spinal cord injuries.

Human induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them human attractive disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as source cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs. We also cover the phenotypic characteristics of the hiPSCs derived CMs, their ability to rescue injured CMs through paracrine effects, the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their potential use in biomedical applications.

Symptoms attributed to the gastrointestinal manifestations of multi-system disorders play an important role in the long-term management of these conditions. Gastrointestinal complications of a variety of connective tissue disorders have been studied and there is an increased interest in the incidence and prevalence of these symptoms. Descriptions of the occurrence of gastrointestinal complications in Marfan syndrome have appeared infrequently in the medical literature. In this review article we focus on both structural and functional gastrointestinal pathology that may occur in patients with Marfan syndrome.

Previous study demonstrated the reconstituted type I collagen matrix extracted from rabbit tendons enabled to regenerate the TMJ disc in the rabbit. The aim of this study was to investigate changes in the extracellular matrix (ECM) and mechanisms of regeneration in TMJ disc. In 36 New Zealand rabbits that underwent a partial discectomy, discs were replaced with reconstituted collagen templates for 3 months. A histological analysis showed that moderate to severe degeneration appeared in partially discectomized joints without implantation. In contrast, discs that received the reconstituted collagen template regenerated, and returned to normal to protect the joint. Cells in the regenerative tissue expressed ECM, and fibers became regular and compact due to tissue remodeling over time. Reparative cells differentiated into chondroblasts, and showed highly dense pericellular fibers. The morphology and collagen composition of the disc and condyle in the 3-month experimental group were similar to those of normal tissues. In conclusion, the reconstituted collagen template facilitated the regeneration of surgically discectomized discs. Type I and type II collagens play a crucial role in the regeneration of articular discs.

Metabolomic analysis of biological fluids and tissues has become an increasingly routine tool in the biological toolbox. However, challenges remain to be overcome, including developing strategies to maximise coverage of the metabolome without requiring large sample volumes. Here we describe a multimodal strategy that combines data using both LC-MS and GC-MS from a unique vial with a sample of plasma (20µl) or a sample of brain tissue (3mg). Using a split phase extraction the non-aqueous phase was analyzed by reversed phase (RP) LC-MS, whilst the aqueous phase was analyzed using hydrophilic liquid interaction chromatography (HILIC)LC-MS, with both phases also analysed using GC-MS after derivatization of the extract. Analytical performance was assessed in 7 rat cerebellum samples and a pilot study of 40 plasma samples (20 vs. 20: AD vs. healthy controls). The method, which uses four hours of instrument time, measured 20,707 metabolite features in brain samples and 17,266 in plasma samples, from those 44.1% features displayed CV’s below 15% and 75.2% below 30%. The method has potential to resolve subtle biological differences and to correlate metabolite composition directly to clinical outcomes including MMSE, age and ADCS-ADL. This method can acquire in the order of 20K metabolic features when low volumes are available.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

Obesity-associated metabolic abnormalities comprise of a cluster of conditions including dyslipidemia, insulin resistance, diabetes, and cardiovascular diseases that has affected more than 650 million people all over the globe. Obesity results from accumulation of white adipose tissues mainly due to the chronic imbalance of energy intake and energy expenditure. Variety of approaches to treat or prevent obesity, including lifestyle interventions, surgical weight loss procedures and pharmacological approaches to reduce energy intake and increase energy expenditure have failed to substantially decrease the prevalence of obesity. Brown adipose tissue (BAT), the primary source of thermogenesis in infants and small mammals may represent a promising therapeutic target to treat obesity by promoting energy expenditure through non-shivering thermogenesis mediated by mitochondrial uncoupling protein 1 (UCP1). Since the confirmation of functional BAT in adult humans by several groups, approximately a decade ago and its association with a favorable metabolic phenotype, intense interest on the significance of BAT in adult human physiology and metabolic health has emerged within the scientific community to explore its therapeutic potential for the treatment of obesity and metabolic diseases. Substantially decreased BAT activity in individuals with obesity indicates a role for BAT in setting of human obesity. On the other hand, BAT mass and its prevalence has been reported to correlate with lower body mass index (BMI), decreased age and glucose levels, leading to lower incidence of cardio metabolic diseases. Increased cold exposure in adult humans with undetectable BAT was associated with decreased body fat mass and increased insulin sensitivity. Deeper understanding of the role of BAT in human metabolic health and its inter-relationship with body fat distribution and deciphering proper strategies to increase energy expenditure by either increasing functional BAT mass, or inducing white adipose browning holds the promise for possible therapeutic avenues for the treatment of obesity and associated metabolic disorders.

Ellagitannins (ETs) are the group of tannins found in fruits, nuts and seeds; they undergo hydrolysis in the human digestive tract to form ellagic acid (EA). EA further converted into various forms of Urolithin derivatives (A, B, C, D, M-5, M-6 and M-7) by gut micro biota. Perhaps, the pharmacological properties of said Urolithins were extensively studied, while, little is known about the therapeutic role of synthetic Urolithin-C on oxidative stress induced eryptosis and tissue damage. Therefore, in the current study we investigated the ameliorative role of chemically syn-thesized Urolithin-C on sodium nitrite and Diclofenac (DFC) induced eryptosis and vital organ damage respectively. Urolithin-C was synthesized using chemical method and characterized by High-Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Liquid Chromatography Mass Spectroscopy (LC-MS). The synthesized Urolithin-C scavenged free radicals (DPPH, H2O2) and reduced ferric iron to ferrous iron, revealed its antioxidant activity. The observed antioxidant potential of Uro-lithin-C was investigated in sodium nitrite induced stress in RBC and Diclofenac induced tissue damage in rats. Interestingly, Urolithin-C normalized the sodium nitrate-induced oxidative stress in red blood cells by regulating stress markers, such as lipid peroxidation (LPO), total thiol (TT), and protein carbonyl content (PCC), and endogenous antioxidant enzymes superoxide dis-mutase (SOD) and catalase (CAT) in a dose dependent manner. Similar effect was also observed in the tissue homogenates of liver, kidney, heart and pancreas taken from the Diclofenac injected Sprague Dawley rats. The tissue sections (liver, kidney, heart and pancreas) obtained from the Diclofenac (DFC) received rats showed massive destruction of hepatocytes, nephrons, cardiocytes and pancreas. However, Urolithin-C received rats tissue sections showed normal histology compared to the positive (Silymarin) control treated groups. In addition, Urolithin-C regulated the key tissue specific biochemical markers in DFC injected Sprague Dawley rats serum strengthened its tissue protective role. In conclusion, chemically synthesized Urolithin-C regulated NaNO2 and diclofenac induced oxidative stress in RBC and vital organs through its antioxidant property.

1) Background: Overweight children usually have lower levels of physical activity (PA) than their normal-weight peers. Low PA predisposes to increase fat mass in the body. The aim of this study was to evaluate the effectiveness of school-based PA intervention on anthropometric indicators and body composition of overweight and obese children during a two-year observation period, from the age of 10 to 12. (2) Materials and methods: The research included 148 children with overweight or obesity who were born in 2007. There were two groups of children of standard and elevated PA at school (SPA and EPA, 4 and 10 hours of physical education lessons a week, respectively). An anthropometric and body composition measurements were done. Body mass index (BMI), fat mass (FM), fat-free mass (FFM), skeletal muscle mass (SMM) and total body water (TBW) were determined. Totally, 5 measurements were done at intervals of 5–6 months. (3) Results: In EPA, the percentage of obese children decreased from 46% to 35.25%, and in SPA increased from 42.75% to 46%. In EPA, FM decreased from 28.65% to 26.41%, and in SPA increased from 30.31% to 31.75%. The highest increase in FFM was in EPA boys, while SPA boys recorded the highest decrease. In SPA, SMM increased by 0.43% from 38.85% to 39.28%, and in EPA by 2.51% from 40.27% to 42.78%. TBW In EPA slightly increased from 53.26% to 53.59%, and in SPA decreased from 50.70% to 49.93%. (4) Conclusions: The elevated PA at school has a positive effect on the BMI and body composition of children who are overweight or obese. Increasing the mandatory number of physical education lessons in school curricula is an efficient strategy for reducing obesity in school-aged children.

Cymbidium faberi Rolfe is one of the traditional Chinese orchids with important ornamental value, and the cultivation of Cymbidium faberi Rolfe mutant strains with different appearances is essential to increase its economic value, but at present, the acquisition of Cymbidium faberi Rolfe mutant strains basically relies on natural mutation.The objectives of this research were to mutagenize Cymbidium faberi Rolfe protocorm-like bodies (PLBs) and shoots in vitro using sodium azide (NaN3), and to screen and evaluate mutants in mutagenized Cymbidium faberi Rolfe seedlings using morphological characteristics.Cymbidium faberi Rolfe PLBs and shoots were used as mutagenic materials, and co-cultivated in induced shoots growth medium with the addition of 0.0 (control), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 mg/L and 0.0 (control), 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, and 10.0 mg/L NaN3 to induce the mutations, and the mortality rates of the PLBs and shoots were increased with the increase of the NaN3 concentration.At 14 d of co-cultivation, PLBs and shoots were most efficiently mutagenized with 1.5 mg/L and 4.0 mg/L NaN3, respectively.After the explants were cultured for 3 months, changes in leaf and flower morphology were observed in some mutants: shorter and thicker leaves, shorter node length, reduced height, and mid-translucent leaves compared with controls; and some Cymbidium faberi Rolfe bloomed prematurely, with single flowers with large, thick petal sepals and small inflorescences, and colours include light green throughout, and a few with purple stamens.This suggests that NaN3 can effectively mutagenise Cymbidium faberi Rolfe PLBs and shoots to satisfy people's demand for Cymbidium faberi Rolfe's ornamental properties while increasing its economic value.

Fabrication of scaffolds via 3D printing is a promising approach for tissue engineering. In this study, we combined 3D printing with cryogenic crosslinking to create biocompatible gela-tin/oxidized alginate (Gel/OxAlg) scaffolds with large pore sizes, beneficial for bone tissue re-generation. To enhance the osteogenic effects and mechanical properties of these scaffolds, we evaluated the impact of hydroxyapatite (HAp) on the rheological characteristics of the 2.86% (1:1) Gel/OxAlg ink. We investigated the morphological and mechanical properties of scaffolds with low, 5% and high 10% HAp content, as well as the resulting bio and osteogenic effects. Scanning electron microscopy revealed a reduction in pore sizes from 160-180 µm (HAp-free) to 120-140 µm for both HAp-containing scaffolds. Increased stability and higher Young’s moduli were measured for 5% and 10% HAp (18 and 21 kPa, respectively) compared to 11 kPa for HAp-free constructs. Biological assessments with mesenchymal stem cells indicated excellent cytocompati-bility and osteogenic differentiation in all scaffolds, with high degree of mineralization in HAp-containing constructs. Scaffolds with 5% HAp exhibit improved mechanical characteristics and shape fidelity, demonstrate positive osteogenic impact, and enhance bone tissue formation. Increasing the HAp content to 10% did not show any advantages in osteogenesis, offering a minor increase in mechanical strength at the cost of significantly compromised shape fidelity.

Preconditioned mesenchymal stem cells (MSCs) represent an advanced method to overcome the challenges related to their survival rate, differentiation, and activity maintenance. L-carnitine has demonstrated antioxidant and anti-apoptotic effects on injured cardiac cells. However, limited research has been conducted to explore their combined effect on cardiac tissue injury. Therefore, the present study aimed to conduct a comparative and comprehensive study investigating the role of L-carnitine-pre-treatment on the immunomodulation of inflammation, apoptosis, and differentiation of MSCs and their impact on cardiac toxicity induced by Doxorubicin (DOX). Rats were divided into group I (control), group II (DOX), group III (DOX+MSCs), group IV (DOX+L-carnitine), group V (DOX+L-carnitine pre-treated MSCs). CK-MB, troponin I, MDA, and catalase levels were improved in the treated groups (III, IV, and V). The degeneration and necrosis of the cardiomyocytes were reduced in the treated groups. They regained their normal architecture in the L-carnitine pre-treated MSCs group. These findings were augmented by analyzing the immunomodulators; NF-ҡβ, TNFα, and IL-1β, the proliferative indicators Ki-67, and hsp90, the cardiac differentiation marker TH and the apoptotic regulators; caspase 3 and Bcl2. These results demonstrate the optimal regenerative and therapeutic effects of L-carnitine pre-treated MSCs representing an efficient tool for future stem cell therapy.

The external and internal structures of male and female adults of Culicoides grisescens Edwards, were examined with scanning electron microscope (SEM) and tissue section techniques. Specimens were collected from Qilian Mountain National Park in Qinghai Province, China. The ultrastructure and morphology of compound eyes, antenna, maxillary palpus, spermathecae, genitalia and other structural characteristics of both male and female adults of C. grisescens are described. Internal structures of the species are described, including histological sections of the digestive, nervous, respiratory, and reproductive systems. This paper provides visual and descriptive details for the systematic taxonomic study of Ceratopogonidae.

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (version 2.0) contains increased 24,145 predicted genes from previous version (24317 genes) with a higher BUSCO value of 96.9%. 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjust genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserve their original des ignations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using newly obtained transcriptome data with the revised gene prediction model. This improved annotation of cucumber genome will provide essential and accurate resources for studies in cucumber.

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-vivo tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

This review provides insight into the role that obesity, but especially mediators of the adipose tissue, have in both renal disease and transplantation. In particular, we focus on the functions of leptin and adiponectin, inflammatory mediators with widely known clinical implications, as well as on the role of arachidonic acid-derived eicosanoid metabolites. These latter compounds, epoxyeicosatrienoic (EETs) and hydroxyeicosatetraenoic (HETEs) acids, which modulate the liberation of cytokines in the adipose tissue, are generated in the epoxygenase pathway of arachidonic biotransformation via CYP450 enzymes. There is accumulating evidence suggesting that EETs and HETEs may have a critical role in the onset and outcome of chronic kidney disease and renal transplantation. Finally, we also discuss the reported effect that the presence of genetic variants in leptin, adiponectin, EETs and HETEs-related genes may cause in renal patients and recipients. The levels of cytokines of the adipose tissue and related compounds play a remarkable role in both renal disease and transplant. Accordingly, novel therapeutic strategies are being developed based on the modulation of their concentrations in patients with various diseases.

Bacteriotherapy is emerging as a strategic and effective approach to treat infections by providing putatively harmless bacteria (i.e., probiotics) as antagonists to pathogens. A proper delivery of probiotics or their metabolites (i.e., post-biotics) can avail itself of biomaterial encapsulation by innovative manufacturing technologies. This review paper aims at providing the most recent biomaterial-assisted strategies proposed to treat infections or disbiosis using bacteriotherapy. We revised the encapsulation processes across multiscale biomaterial approaches, which could be ideal to target different tissues and suit diverse therapeutic opportunities. Hydrogels, and in particular polysaccharides, are the focus of this review, as they have been reported to better sustain vitality of the live cells incorporated. Specifically, the approaches for fabricating hydrogel-based devices with increasing dimensionality (D), namely, 0D (i.e., particles), 1D (i.e., fibers), 2D (i.e., fiber meshes), and 3D (i.e., scaffolds) endowed with probiotics, were detailed by describing their advantages and challenges, along with a future overlook in the field. Electrospinning, electrospray and 3D bioprinting were investigated as new biofabrication methods for probiotic encapsulation within multidimensional matrices. Finally, examples of biomaterial-based systems for cell and post-biotic release were reported.

Hydrogels prepared from natural polymer have attracted extensive attentions in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid and starch. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical application of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing and other biomedical field is summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymer, novel technologies such as enzymatic and biological methods are developed to improve the structural properties and the development of new natural based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels and hydrogel microrobots are designed to meet the advanced requirements in biomedical application, and new strategies such as dual-crosslinking, microfluidic chip, micropatterning and 3D/4D bioprinting, have been explored to fabricate advanced hydrogel materials with designed properties for biomedical application. Overall, natural polymeric hydrogels have attracted increasing interests in biomedical application, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication is badly desirable and still challenging.

Adipose tissue has acquired considerable importance due to its role in maintaining body homeostasis. Beyond storing energy, adipose tissue is essential in numerous processes of energy metabolism, food intake, endocrine and immunological functions as well as neromodulatory functions by secreting hormones that participate in the regulation of homeostasis and being responsive to soluble proteins secreted by other tissues. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favouring the secretion of deleterious adipocytokines that benefit a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases. Obesity is a disease that has increased rapidly in recent decades and is caused by environmental, hormonal, and genetic factors, which probably work in combination. Environmental factors that contribute to the increase in obesity include decreased physical activity, associated with increased screen time, increased accessibility and consumption of foods rich in fats and sugars. Weight loss should be recommended for all obese patients and overweight patients with comorbidities. For many patients who need to lose weight for medical reasons, the initial goal is to lose 5-10% of their body weight in the first 6 months. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity and in Chile, the Chilean Society of Metabolic and Bariatric Surgery led the process of adopting the adult obesity clinical practice guideline, which establishes changes in the approach to managing obesity as a chronic disease, with an emphasis on multifactorial lifestyle interventions that include dietary changes, increased physical activity, and behavioural modifications. Pharmacotherapy, medical devices, and bariatric surgery are other options for patients who need additional interventions, so the objective of this review is to know the pathophysiological mechanisms of obesity from its origin to the current treatments available for treatment.

Hydrogels (gels) are attractive tools for tissue engineering and regenerative medicine due to their potential for drug delivery and ECM-like composition. In this study, we use rheology to characterize GelMA/alginate gels loaded with human platelet lysate (PL). We then characterize these gels from a physicochemical perspective and evaluate their ability to transport PL proteins, their pore size, and their rate of degradation. Finally, their biocompatibility is evaluated. We describe how alginate changes the mechanical behavior of the gels from elastic to viscoelastic after ionic (calcium-mediated) crosslinking. In addition, we positively report the release of PL proteins and relate it to the degradation profile of the gels and the biocompatibility of the gels. Thus, the developed gels represent attractive substrates for both cell studies and bioactive materials.

Drought is an important factor seriously affects agricultural production worldwide. Agricultural practices that can increase resistance to drought are gaining importance. In this study the role of nano-silicon dioxide (NaSiO2) in countering drought stress in invitro strawberry plantlets were investigated. In the experiment, the effects of PEG 6000 concentrations (0, 4, 8%) and NaSiO2 concentrations (0, 50, 100 mg L-1) on invitro strawberry plants were determined. Plantlets treated with PEG 6000 showed reduced vegetative growth parameters, but this decrease was reduced with NaSiO2 application. NaSiO2 at 50 mg L−1 induced the maximum shoot and root fresh weight (1.20 g, 1.24 g, respectively) and length (40.09 mm, 34.26 mm, respectively), leaves number (16.67 pieces/plant) and SPAD index 53.57 among 4% and 8% PEG applications. When the SOD and CAT activities were examined, the results showed that application of NaSiO2 enhancement drought stress tolerance by promoted certain antioxidant response by increasing SOD and catalase (CAT) activities under drought stress. According to the results NaSiO2, limited the devastating impact of drought stress and markedly enhanced all the examined parameters.

Development of bioresponsive extrudable hydrogels for 3D bioprinting is imperative to address the growing demand for scaffold design and efficient and reliable methods of tissue engineering and regenerative medicine. This study proposed genipin-crosslinked gelatin-hyaluronic acid hydrogel bioink with different amounts of gelatin tailored for 3D bioprinting, focusing on high cell density loading and less artificial extra-cellular matrix (ECM) effect, as well as exploring their potential applications in tissue engineering. The bioresponsiveness of these hydrogel scaffolds was successfully evaluated in different physiological conditions. 3D and four-axis printing of complex structures such as shapes of hollow tube, star, pyramid, and four-axis tubular scaffolds prove the hydrogel’s high extrusion ability and post-printing shape fidelity. Cytocompatibility and high cell density 3D bioprinting using this moderately stable hydrogel exhibit high potential for precise cell-delivery modes in tissue engineering as well as regenerative medicine.

This paper presents a combined optical imaging/artificial intelligence (OI/AI) technique for real-time analysis of tissue morphology at the tip of the biopsy needle, prior collecting a biopsy specimen. This is an important clinical problem as up to 40% of the collected biopsy cores provide low diagnostic value due to high adipose or necrotic content. Micron-scale resolution optical coherence tomography (OCT) images can be collected with a minimally invasive needle probe and automatically analyzed by a computer neural network (CNN)-based AI software. The results can be conveyed to the clinician in real-time and used to select the biopsy location more adequately. This technology was evaluated on a rabbit model of cancer. OCT images were collected with a hand-held custom-made OCT probe. Annotated OCT images were used as ground truth for AI algorithm training. The overall performance of the AI model was very close to that of the humans performing the same classification tasks. Specifically, tissue segmentation was excellent (~99% accuracy) and provided segmentation that closely mimicked ground truth provided by the human annotations, while over 83% correlation accuracy was obtained for tumor and non-tumor classification.

3D bioprinting is the process of manipulating cell-laden bioinks to fabricate living structures. 3D bioprinting techniques have brought considerable innovation in biomedicine, especially in the field of tissue engineering, allowing the production of 3D organ and tissue models for in vivo transplantation purposes or for in-depth and precise in vitro analyses. Natural-derived hydrogels, especially those obtained from the decellularization of biological tissues, are promising bioinks for 3D printing purposes, as they present the best biocompatibility characteristics. Despite this, many natural hydrogels do not possess the necessary mechanical properties to allow a simple and immediate application in the 3D printing process. In this review, we focus on the bioactive and mechanical characteristics that natural hydrogels may possess to allow efficient production of organs and tissues for biomedical applications, emphasizing the reinforcement techniques to improve their biomechanical properties.

Ingrown toenails are a commonly occurring foot complaint. The condition occurs when the nail plate pierces the sulcus, giving rise to pain, inflammation and infection. As the skin attempts to heal itself, hypergranulation tissue may form. This is a case report of phenolic nail surgery treatment for a bilateral presentation with sharp resection of hypergranulation tissue performed in only one (the lateral) of the two affected sulci. Sharp resection of the residual medial hypergranulation tissue was performed two months after the index procedure when this had not settled. The case highlights the potential role of sharp resection in the overall improvement of treatment outcomes.

Objectives: The promising specific growth regulators are employed tissue culture of the bamboo species. The specific natural hardening mixture supports the acclimatization and adaptation of the protected cultivation. The bamboo species contribute to the carbon sequestration and stabilization of the environment. Findings: The growth regulator 2, 4-D encourages callus induction and growth regulators NAA + TDZ, BAP + Kinetin + Gelrite, BAP + Kinetin + Coconut water + myo-inositol, NAA and TDZ impose plant regeneration in the Bambusa species. The growth regulator of 2,4-D, 2,4-D + Kinetin, 2,4-D + BA, 2,4-D + BAP and 2,4-D + NAA + BAP produces callus induction in the Dendrocalamus species. The growth regulator of TDZ, BA and IBA + Coumarin + Putrescine, BAP + GA3, NAA + Kinetin, BA + IBA, BA + Kinetin + NAA, NAA + Kinetin, Kinetin + IAA has facilitated shoot regeneration in the Dendrocalamus species with the specific period. The growth regulator of BA and TDZ; BAP + TDZ, IBA + Coumarin + Putrescine, BAP + GA3, NAA + Kinetin, BA + IBA, BA + Kinetin + NAA, NAA + Kinetin, Kinetin + IAA develops root regeneration with unambiguous time in the Dendrocalamus species. The growth regulator of BAP and Kinetin + BAP imposes shoot regeneration and IBA and IBA + Coumarin + sucrose conducts root regeneration in the edible bamboo. The natural hardening materials of cocopeat, vermicompost, perlite, cow dung, FYM, compost, soil & garden soil and humus soil, perlite, and FYM recommend in the acclimatization and adaptation of the Bambusa species and Dendrocalamus species respectively. Novelty: The standard growth regulators and hardening mixtures impose tissue culture, acclimatization and adaptation in the bamboo species. The bamboo species involves in managing carbon sequestration, biogeochemical cycle and the environment.

Brain tissue segmentation is an important component of clinical diagnosis of brain diseases by means of multi-modal magnetic resonance imaging (MR). Brain tissue segmentation is developed by many unsupervised methods in literature. The most commonly used unsupervised methods are: K-Means, Expectation Maximization and Fuzzy Clustering. Fuzzy clustering methods offer considerable benefits compared with the aforementioned methods as they are capable of handling brain images which are complex, largely uncertain and imprecise in nature. However, this approach suffers from the intrinsic noise and intensity inhomogeneity (IIH) in the data resulted from the acquisition process. To resolve these issues, we propose a fuzzy consensus clustering algorithm that defines a membership function resulted from a voting schema to cluster the pixels. In particular, we first pre-process the MRI data and employ several segmentation techniques based on traditional fuzzy sets and intuitionistic sets. Then, we adopted a voting schema to fuse the results of the applied clustering methods. Finally, to evaluate the proposed method, we used the well-known performance measures (boundary measure, overlap measure and volume measure) on two publicly available datasets (OASIS and IBSR18). The experimental results show the superior performance of the proposed method in comparison with the recent state of the arts.

There are various biomaterials in nature, but none fulfills all the requirements. Cellulose, eco-friendly material-based biopolymers, have been advanced biomedicine to satisfy most market demand and circumvent many ecological concerns. This review aims to present an overview of the state of the art in cellulose's knowledge and technical biomedical applications. It included an extensive bibliography of recent research findings for fundamental and applied investigations. The chemical structure of cellulose allows modifications and simple conjugation with several materials, including nanoparticles, without tedious efforts. Cellulose-based materials were used for biomedicine applications such as antibacterial agents, antifouling, wound healing, drug delivery, tissue engineering, and bone regeneration. They advanced the applications to be cheap, biocompatible, biodegradable, easy for shaping and processing into different forms, with suitable chemical, mechanical and physical properties.

Hearing dysfunctions can be classified by type, degree, configuration, time of onset, aetiology, and finally, consequences on speech development. They can be divided into conductive, mixed, central types and sensorineural. Conductive hearing loss (CHL) results from interference with the mechanical transmission of sound through the external and middle ear; it can be congenital, as a consequence of anatomic abnormalities, but it can commonly be acquired following middle ear inflammatory pathologies. Sensorineural hearing loss (SNHL) results from failure to transduce vibrations to neural impulses in the cochlean and is a consequence of an irreversible damage to the differentiated cells which make up the organ of hearing and the acoustic paths at various levels. Mixed hearing loss involves a combination of these two types in the same ear. Studies in neuroscience field have shown that the prevention of cell degeneration is only possible if all the factors taken at the different stages of stem cells’ multiplication and differentiation are administered together. We have demonstrated this in a recent study on the ability of SCDSFs to prevent neurodegeneration in hippocampal cells of the CA1 zone in mice. This study confirms previous findings demonstrating that early developmental zebrafish embryo extracts could act as a modulator of senescence in human mesenchymal stem cells (hMSC) isolated from many adult tissues. These findings have open a promising way for the approaches promoting the rejuvenation and regeneration of different tissues, by-passing stem cell transplantation. In the present clinical trial we have used SCDSFs to study the possible reversion of neurosensory hearing loss, until now considered an irreversible condition.

In the present study, we aimed to investigate whether an automated molecular diagnostic method based on PCR-reverse blot hybridization assay can discriminate between human Mycobacterium tuberculosis (MTB)-positive and -negative FFPE tissues and to compare the relative mRNA expression levels of various host immune markers between MTB-infected and uninfected human tissues using quantitative reverse transcription (qRT) PCR. A total of 52 human FFPE tissue samples from various regions of the body, including the lungs, lymph nodes, tendons, colon, and appendix, were collected and used for the molecular identification of Mycobacterium species and analysis of cytokine mRNA expression. As a result, IFN-γ, TNF-α, IP-10, CXCL9, CXCL11, and GM-CSF mRNA expression levels in MTB-infected tissues were significantly higher than those in uninfected samples. Additionally, the differences in the mRNA expression levels of IFN-γ, CXCL9, and GM-CSF between MTB-infected and uninfected tissues were statistically significant were statistically significant (p < 0.05). Correlation curve analysis indicated that the mRNA expression of IFN-γ was inversely proportional to that of IP-10 and that the mRNA expression levels of IFN-γ, TNF-α, CXCL9, CXCL11, GM-CSF, and TNFR were proportional and well-correlated. Furthermore, to establish marker profiles for detecting MTB infection, the statistically significant expression levels of three markers were combined. We confirmed that the combined profile of IFN-γ, CXCL9, and GM-CSF expression levels was statistically significant (P < 0.001). Although the mRNA expression patterns of host immune markers may vary according to MTB infection status, these patterns may be highly correlated and can be simultaneously used as an additional indicator for diagnosing TB.

Scaffolds are widely used in tissue engineering because their manufacture is based on natural and synthetic polymers, which allows them to have properties such as biocompatibility and biodegradability, creating an ideal environment for cell growth on their surface. In this context, among the polymers studied in Tissue Engineering are Chitosan (CH) and Polyvinyl Alcohol (PVA). CH is a versatile polymer obtained from de-acetylation of chitin, which is used for its high biodegradability and biocompatibility, although its mechanical properties must be improved. It has been found that one of the ways to improve the mechanical properties of CH is to mix it with other synthetic polymers such as PVA. PVA is known for its biocompatibility, biodegradability, zero toxicity and ease of preparation due to its solubility in water and excellent mechanical properties, such as tensile strength and ease in the formation of films and barriers. In this study we evaluated the capacity of scaffolds made with CH and PVA in different concentrations (2: 1, 1: 1, 1: 2, respectively) as a possible application in bone regeneration. This was made through different characterization tests such as Infrared Spectroscopy, AFM, Swelling test and Porosity test, where we obtained information about its structural and physicochemical properties. Additionally, a cellular quality control was performed on the material through the MTT assay. The Fourier transform infrared spectroscopy (FTIR) study showed that there are strong intermolecular hydrogen bonds between the chitosan and polyvinyl alcohol molecules. The Swelling and Porosity tests showed favorable results, obtaining maximum values ​​of 5519% and 72.17% respectively. MTT tests determined that the prepared materials are not cytotoxic. These findings suggest that scaffolds possess properties suitable for use in Tissue Engineering.

Cranio-maxillofacial structure is a region of particular interest in the field of regenerative medicine due to both its anatomical complexity and the numerous abnormalities affecting this area. However, this anatomical complexity is what makes possible the coexistence of different microbial ecosystems in the oral cavity and the maxillofacial region, contributing to the increased risk of bacterial infections. In this regard, different materials have been used for their application in this field. These materials can be obtained from natural and renewable feedstocks or by synthetic routes with desired mechanical properties, biocompatibility and antimicrobial activity. Hence, in this review, we have focused on bio-based polymers, which by their own nature, by chemical modifications of their structure, or by their combination with other elements, provide a useful antibacterial activity as well as the suitable conditions for cranio-maxillofacial tissue regeneration. This approach has not been reviewed previously, and we have specifically arranged the content of this article according to the resulting material and its corresponding application, reviewing guided bone regeneration membranes; bone cements; and devices and scaffolds for both soft and hard maxillofacial tissue regeneration, including hybrid scaffolds, dental implants, hydrogels and composites.

Three-dimensional (3D) bioprinting promises to be essential in tissue engineering for solving the rising demand for organs and tissues. Some bioprinters are commercially available, but their impact on the field of TE is still limited due to their cost or difficulty to tune. Herein, we present a low-cost easy-to-build printhead for microextrusion-based bioprinting (MEBB) that can be installed in many desktop 3D printers to transform them into 3D bioprinters. We can extrude bioinks with precise control of print temperature between 2 - 60 ºC. We validated the versatility of the printhead, by assembling it in three low-cost open-source desktop 3D printers. Multiple units of the printhead can also be easily put together in a single printer carriage for building a multi-material 3D bioprinter. Print resolution was evaluated by creating representative calibration models at different temperatures using natural hydrogels such as gelatin and alginate, and synthetic ones like poloxamer. Using one of the three modified low-cost 3D printers, we successfully printed cell-laden lattice constructs with cell viabilities higher than 90% after 24h post printing. Controlling temperature and pressure according to the rheological properties of the bioinks was essential in achieving optimal printability and great cell viability. The cost per unit of our device, which can be used with syringes of different volume, is less expensive than any other commercially available product. These data demonstrate an affordable open-source printhead with the potential to become a reliable alternative to commercial bioprinters for any laboratory.

The aim of performed studies was to fabricate an antibacterial and degradable scaffold that may be used in the field of skin regeneration. To reach the degradation criterion the biocompatible polyurethane (PUR), obtained by using amorphous macrodiol α,ω-dihydroxy(ethylene-butylene adipate) macrodiol (PEBA), was used and processed with so-called “fast-degradable” polymer polylactide (PLA) (5 wt% or 10 wt%). To meet the antibacterial requirement obtained hybrid PUR-PLA scaffolds (HPPS) were modified with ciprofloxacin (Cipro) (2 wt% or 5 wt%), the fluoroquinolone antibiotic inhibiting growth of bacteria such as Pseudomonas aeruginosa, Escherichia Coli and Staphylococcus aureus, which are main cause of wound infections. Obtained unmodified and Cipro-modified HPPS were studied towards their chemical composition to detect presence or absence of characteristic functional groups of PUR, PLA and Cipro, and as well to indicate the participation of hydrogen bonds in the HPPS structure in dependence on PLA addition and ciprofloxacin modification. Mechanical properties were studied to determine the possible application of HPPS as a skin tissue scaffold. Scanning electron microscopy (SEM) was used to study morphology of unmodified and Cipro-modified HPPS and to performed elementary analysis by using energy-dispersive x-ray spectroscopy (EDX) of obtained materials. Finally, the microbiological tests were performed to indicate the antibacterial effect of Cipro-modified HPPS on S.aureus growth. Performed studies showed that Cipro-modified HPPS, obtained by using 5 % of PLA, possess suitable mechanical characteristic, morphology, degradation rate and demanded antimicrobial properties to be further developed as a potential scaffolds for skin tissue engineering.

Background: This study aimed to describe the frequency and duration of sedentary bouts and assess the bidirectional cross-sectional associations between these characteristics and adiposity in elderly women. Methods: Data from 314 elderly community-dwelling women (mean age 66.6±6.5 years) from Czech Republic, Poland, and Slovakia were analyzed. Measures were collected in 2008–2017. Fat mass percentage (FM%) was used as an indicator of adiposity. The patterns of sedentary behaviour were monitored using an accelerometer, and ≥5, ≥10, ≥20, ≥30, ≥40, and ≥60 minute bouts were analyzed. The exponent alpha was also calculated to express the accumulation of sedentary time in bouts. We performed a multiple linear regression analysis to assess the bidirectional causal association between variables. Results: There was a significant association of FM% with time spent in bouts with a duration ≥5, ≥10, ≥20min (β ranging 0.11–0.28, p≤0.01) and the frequency of bouts with a length ≥5, ≥10, ≥20, and ≥30min (β ranging 0.03–0.74, p≤0.05) in fully-adjusted models. In contrast, a strong negative association was observed between FM% and alpha (bout distribution) in both directions (p≤0.001). Conclusions: Our results suggest that the sedentary characteristics such as bout duration, bout frequency, and distribution (alpha) are bidirectionally associated with adiposity and they should be considered in further research in older adults.

Cancer is a leading cause of morbidity and mortality worldwide, yet much is still unknown about its mechanism of establishment and destruction. Recently, studies had shown that tumor cells cannot survive under the high temperature conditions. This treatment technique is called Hyperthermia. This report presents the case of radiative microwave heating of hyperthermia therapy on breast cancer in a porous medium. In this study, the steady state is solved analytically while unsteady state is solved using semi-implicit finite difference to get a more accurate prediction of blood temperature distributions within the breast tissues. A moderate temperature hyperthermia treatment is apply which results into cell death due to an increase in the level of cell sensitivity to radiation therapy and blood flow in tumor and oxygen. The results show that by applying metabolic heat generation rate of $3.97 X 10^{5}Wm^{-3}$, it takes upto 2 minutes for the tumor cells to get the require therapeutic temperature point.

Background: Traditional root canal therapy (RCT) has been the primary method for treating necrotic pulp, but it presents limitations such as loss of vitality and postoperative fractures. Recent advancements in regenerative endodontics offer alternative strategies to restore pulp tissue vitality and function. These approaches involve stem cell transplantation, cell homing, and the use of organic scaffolds to promote pulp regeneration. Highlight: This article reviews various regenerative endodontic techniques, including autogenic and allogenic dental pulp transplantation, the use of amniotic membrane scaffolds, platelet-rich fibrin therapy, specialized pro-resolving mediators, nanofibrous and bioceramic-based scaffolds, injectable scaffolds, and dentin matrix proteins. These strategies leverage stem cells, growth factors, and biomaterials to create conducive microenvironments for cell attachment, proliferation, and differentiation, thereby facilitating pulp tissue regeneration. Methods: The literature search was conducted using databases such as PubMed, Scopus, and Google Scholar, employing keywords like "regenerative endodontics," "pulpitis," "pulp regeneration," and "platelet-rich fibrin." Conclusion: The reviewed approaches in regenerative endodontics show promising potential for overcoming the limitations of traditional RCT and promoting pulp tissue regeneration. However, further research is needed to optimize protocols, address challenges, and translate these advancements into routine clinical practice. Ultimately, these innovations have the potential to enhance patient outcomes in endodontic treatment by restoring pulp vitality and function effectively.

Inherited heart diseases (IHDs) are caused by genetic mutations that disrupt the physiological structure and function of the heart. Understanding the mechanisms behind these diseases is crucial for developing personalised interventions in cardiovascular medicine. Development of induced pluripotent stem cells, which can then be differentiated to any nucleated adult cell type, has enabled the creation of personalised single-cell and multicellular models, providing unprecedented insights into the pathophysiology of IHDs. This review provides a comprehensive overview of recent advancements in human iPSC models used to dissect the molecular and genetic underpinnings of common IHDs. We examine multicellular models and tissue engineering approaches, such as cardiac organoids, engineered heart tissue, and multicellular co-culture systems, which simulate complex intercellular interactions within heart tissue. Recent advancements in stem cell models offer a more physiologically relevant platform to study disease mechanisms, enabling researchers to observe cellular interactions, study disease progression, and identify therapeutic strategies. By leveraging these innovative models, we can gain deeper insights into the molecular and cellular mechanisms underlying IHDs, ultimately paving the way for more effective diagnostic and therapeutic strategies.

Background: Obesity remains a widely debated issue, often criticized for the limitations in its identification and classification. This study aims to compare two distinct systems for classifying obesity: Body Mass Index (BMI) and body fat percentage (BFP) as assessed by bioelectrical impedance analysis (BIA). By examining these measures, the study seeks to clarify how different metrics of body composition influence the identification of obesity-related risk factors. Methods: The study enrolled 1255 adults, comprising 471 males and 784 females, with a mean age of 36 ± 11.90 years. Participants exhibited varying degrees of weight status, including optimal weight, overweight, and obesity. Body composition analysis was conducted using the TANITA Body Composition Analyzer BC-418 MA III device (T5896, Tokyo, Japan), evaluating the following parameters: current weight, basal metabolic rate (BMR), adipose tissue (%), muscle mass (%), and hydration status (%). Results: Age and psychological factors like cravings, fatigue, stress, and compulsive eating were significant predictors of obesity in the BMI model but not in the BFP model. Additionally, having a family history of diabetes was protective in the BMI model (OR: 0.33) but increased risk in the BFP model (OR: 1.66). The BMI model demonstrates exceptional predictive ability (AUC=0.998). In contrast, the BFP model, while still performing well, exhibits a lower AUC (0.975), indicating slightly reduced discriminative power compared to the BMI model. Conclusions:BMI classification demonstrates superior predictive accuracy, specificity, and sensitivity. This suggests that BMI remains a more reliable measure for identifying obesity-related risk factors compared to the BFP model.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but is critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterioembolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels' elastic modulus (G'), loss modulus (G''), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from &lt;50 µm to &gt;1 mm. Gel particle size and morphology correlate most significantly with tan(δ). Conversely, arterial flow rates do not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction is affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings highlight the importance of gel viscoelasticity and flow parameters in determining particle size, dispersibility, and occlusive potential.

The integration of modern technologies like intramedullary fixators and advanced biometallic alloys has revolutionized traumatology and orthopedics. While these innovations have improved treatment, the exploration of new materials for implants persists. Tantalum and niobium, both non-toxic with similar properties, are preferred for titanium-based biomedical alloys due to their exceptional biocompatibility and corrosion resistance. Acting as stabilizers in titanium alloys, they form passive oxide layers resisting corrosion and remain compatible with biological systems. The novel Ti21Nb6Ta (TNT) alloy promises enhanced osteosynthesis outcomes. Our in vivo research on experimental animals evaluated the biocompatibility and osteoinduction of TNT compared to Ti-6Al-4V (BT-6) alloy (control group). The study comprised three experiments across different animal species, assessing acute toxicity, irritant effects, and long-term biocompatibility and osteoinduction through simulated osteosynthesis. Results indicated that aqueous extracts from both alloys were non-toxic and non-irritating. Furthermore, both demonstrated high biocompatibility and active osteoinduction potential after three months of implantation.

Background: In most cases, intra-labyrinthine schwannoma (ILS) occurs in patients with unilateral hearing deterioration or neurofibromatosis type II (NF II). The pattern of localization of these tumors is various but affects mostly the cochlea. Extirpation of the ILS, if hidden by the cochlea modiolus, is difficult under the aspect of complete removal. Therefore, a tissue removal device (TRD) was designed and tested in temporal bones. The principle of handling the new device is a pushing and pipe cleaner handling inside the cochlea. This present study aimed to describe the first in vivo experience with the newly developed TRD for removing cochlear intra-labyrinthine schwannoma. Methods: In three patients, the TRD was used for the tumor removal of ILS. In two patients with a cochlear schwannoma in combination with a cochlea implantation and one patient suffering from NF II, a cochlear schwannoma was removed with the TRD. The access was performed with a posterior tympanotomy, an enlarged round window approach, and an additional second-turn access. The device was inserted and extracted gradually from the second turn access until the rings were visible in the second turn access. By pushing and pipe cleaner handling, the tumors were removed. An MRI control was performed on the day postoperatively with a T1 GAD sequence. Results: Tumor removal with the TRD was performed in a 15-minute procedure. MRI control confirmed a complete removal on the postoperative day in both cases. Conclusion: In vivo handling of the device confirmed a straightforward handling for tumor removal. MRI scanning showed a complete removal of the tumor by the TRD.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGen database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined by Mendelian randomization. 253 genes that exerted trans-regulatory impacts on 1,439 genes were identified. Majority of the identified gene-pairs aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. Genes with higher gene expression heritabilities displayed broader regulatory impact in the network. The network displayed the scale-free topology, this provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and higher expression of HHEX is associated with lower triglycerides and risk of type 2 diabetes. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The identified network displayed scale-free topology indicating the hub genes of a tissue-specific network could be targeted to prevent disease outcomes.

Mercury (Hg) pollution not only poses a threat to the environment but also adversely affects the growth and development of plants, with potential repercussions for animals and humans through bioaccumulation in the food chain. Maize, a crucial source of food, industrial materials, and livestock feed, requires special attention in understanding the genetic factors influencing mercury accumulation. Developing maize varieties with low mercury accumulation is vital for both maize production and human health. In this study, a comprehensive genome-wide association study (GWAS) was conducted using an enlarged SNP panel comprising 1.25 million single nucleotide polymorphisms (SNPs) in 230 maize inbred lines across three environments. The analysis identified 111 significant SNPs within 78 quantitative trait loci (QTL), involving 169 candidate genes under the Q model. Compared to the previous study, the increased marker density and optimized statistical model led to the discovery of 74 additional QTL, demonstrating improved statistical power. Gene Ontology (GO) enrichment analysis revealed that most genes participate in arsenate reduction and stress responses. Notably, GRMZM2G440968, associated with the significant SNP chr6.S_155668107 of axis tissue, encodes a cysteine proteinase inhibitor, suggesting its potential role in alleviating Hg toxicity by inhibiting cysteine. Haplotype analyses provided further insights, indicating that lines carrying hap3 exhibited the lowest mercury content compared to other haplotypes. In summary, our study significantly enhances the statistical power of GWAS, identifying additional genes related to mercury accumulation and metabolism. These findings offer valuable insights into unraveling the genetic basis of mercury content in maize and contribute to the development of maize varieties with low mercury accumulation.

In a 24-week-long experiment, 31 rats were assigned to one of 3 groups: a Control group receiving standard chow and water, a Fructose group receiving standard chow and a 20% fructose solution, or an STZ+lipids group that received a fat-enriched diet following a single 25 mg/kg streptozotocin injection at the onset of the diet. Both groups experienced significantly increased caloric intake but did not gain weight above the Control group level. Adipocytes in subcutaneous and visceral adipose depots of both groups had smaller size compared to control and higher density in tissue. Respirometric analyses unveiled a substantial increase in mitochondrial respiration across all adipose tissue types in both dietary intervention groups, with greater changes observed in the Fructose group. Correlation analyses demonstrated that in both experimental groups high tissue respiration is associated with better biochemical profile and closer to control adipose tissue morphology. Increased tissue respiration in adipose depots could be an important mechanism of resilience to excessive caloric intake.

Intrauterine adhesions (IUA) has become one of the main causes of female infertility, how to effectively prevent postoperative re-adhesion has been a clinical challenge. In this study, a mussel-inspired dual-network hydrogel was proposed for postoperative anti-adhesion of IUA. First, calcium alginate/polyacrylamide (CA-PAM) hydrogel was prepared by covalent and Ca2+ cross-linking. Benefiting from abundant phenolic hydroxyl groups, polydopamine (PDA) was introduced to further enhance the adhesion ability and biocompatibility. This CA-PAM hydrogel immersed in 10 mg/mL dopamine solution possessed remarkable mechanical strength (elastic modulus > 5 kPa) and super stretchability (with a breaking elongation of 720%). At the same time, it shown excellent adhesion more than 6 kPa. Surprisingly, the coagulation index of the hydrogel was 27.27 ± 4.91, demonstrating attractive coagulation performance in vitro and the potential for rapid hemostasis after surgery.