In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk aggravating factors for the development of chronic skin lesions. Stem cells regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of 3D bioprinted scaffolds. With this review we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, towards their relevance in the skin regeneration field.

The vertebrate annexin superfamily (AnxA) consists of 12 members of a calcium (Ca²⁺) and phospholipid binding protein family which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca²⁺-controlled regulation of a broad range of membrane events. In this review, we identify and discuss several themes of annexin actions that hold a potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, and that repeatedly surface in the annexin activity profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.

Introduction: Chronic wounds caused by diabetes or lower-extremity artery disease are intractable because the wound healing mechanism is no longer effective due to the poor environment of the wound bed. Biosheet obtained using in-body tissue architecture (iBTA) is a collagen-based membranous tissue that is created within the body and autologously contains various growth factors and somatic stem cells including pluripotent stem cells. When applied to a wound, granulation formation can be promoted and even epithelialization may be achieved. Hearin, we report our clinical treatment experience with seven cases of intractable diabetic foot ulcers. Cases: From 46- to 93-year-old 7 patients had large foot ulcers including heel area, which was failed to heal with standard wound treatment. Methods: Two or four Biosheet-forming molds were implanted subcutaneously in the chest or abdomen, and after 3 to 6 weeks, the molds were removed. Biosheets that formed inside the mold were obtained and applied directly to the wound surface. Results: In all cases, there were no problems with the mold embedding and removal procedures, and Biosheets were formed without any infection or inflammation during the implantation period. The Biosheets were simply applied to the wounds, and in all cases, they adhered within one week, did not fall of, and became integrated with the wound surface Complete wound closure was achieved within 8 weeks in two cases and within 5 months in two cases. One patient was lost due to infective endocarditis from septic colitis. One case required lower leg amputation due to the wound recurrence, and one case achieved wound reduction and wound healing in approximately 9 months. Conclusion: Biotube obtained via iBTA promoted wound healing and were extremely useful for intractable diabetic foot ulcers involving heel area.

Skin wounds and their infections by antibiotic resistant bacteria (ARB)are very common in small animals, posing the risk of acquiring ARB by pet owners or antibiotic resistance gene (ARG) transfer to the owners’ microbiota. The aim of this study was to identify the most common pathogens infecting wounds of companion animals, assess their antibiotic resistance and determine the ARGs using culture-based, molecular and proteomic methods. A total of 136 bacterial strains were isolated from wound swabs. Their species was identified using chromogenic media, followed by MALDI-TOF spectrometry. Disk diffusion was used to test the antibiotic resistance and twelve ARGs were detected using PCRs. The dominant species included Staphylococcus pseudintermedius (9.56%), E. coli and E. faecalis (both n=11, 8.09%). Enterobacterales were mostly resistant to amoxicillin/clavulanic acid (68.3% strains), all Pseudomonas were resistant to ceftazidime, piperacillin/tazobactam, imipenem and tylosin, Acinetobacter was mostly resistant to tylosin (55.5%), all Enterococcus were resistant to imipenem, 39.2% of Staphylococci were resistant to clindamycin. Among ARGs, strA (streptomycin resistance), sul3 (sulfonamide resistance) and blaTEM, an ESBL determinant, were the most frequent. The risk of ARB and ARD transfer between animals and humans causes the need to search for new antimicrobial therapies in the future veterinary medicine.

The modification of cellulose woven fabrics and viscose nonwovens was carried out with the aim of preparing sustainable coatings from biodegradable natural polymers. The modification of fabrics with biodegradable natural polymers represents an ecological alternative to other textile modifications such as the sol-gel process. Coatings were prepared from erythritol, gelatin and collagen in various formulations with the addition of propolis and alginate fibers and a natural plasticizer (glycerin). The morphology of the materials was determined before and after modification with Dino-lite, the pH value, the drop test method, the angle recovery angle, the thickness and the mass per unit area. The modifications have no significant effect on the thickness and mass per unit area, in a larger proportion they show hydrophilic properties, which favours the application for medical purposes - for example the absorption of exudates, wound dressings etc. Due to the neutral and slightly alkaline pH value of the modified samples, they are suitable for external application on the skin. The recovery angle of the modified samples proves that the samples do not tend to crease and that they retain their elasticity after modification and have a pleasant textile feel (fabric hand).

The wound management sector has attracted considerable attention due to the increasing challenge posed by antimicrobial resistance (AMR) and the specialized care required for chronic wounds. Effective wound care involves selecting appropriate dressings tailored with antimicrobial agents to prevent bacterial infection. Among various types of wound dressings, fibers and electrospun fibers, with their unique characteristics, have emerged as innovative new materials. However, the rise of AMR necessitates the exploration of new antimicrobial agents for wound dressings, particularly for addressing bacterial pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Endophytic fungi, known for producing diverse bioactive compounds, including novel antibacterial agents, represent a promising source of such new agents. This study tested thirty-two endophytic fungi from thirteen distinct Australian native plants for their antibacterial activity against S. aureus, the most common wound-associated bacteria. Ethyl acetate (EtOAc) extracts from fungal culture filtrates exhibited inhibitory effects against both methicillin-sensitive S. aureus ATCC 25923 and MRSA strains M173525 and M180920. DNA sequence analysis was employed for fungal identification, with EtOAc extracts from the most active sample, EL 19 (Chaetomium globosum), selected for further bactericidal and antibiofilm testing against the chosen bacteria. Biofilm of S. aureus ATCC 25923 was reduced by 55% by EtOAc extracts of EL 19 at 1/2 × MIC. To demonstrate the potential application in wound dressing materials, three different concentrations of the extract were incorporated into Polycaprolactone fiber mats through electrospinning, with resultant inhibition of S. aureus ATCC 25923 being observed. This research underscores the potential of endophytic fungi from Australian plants as sources of substances effective against common wound pathogens. Further exploration of the responsible compounds and their mechanisms could facilitate the development of wound dressings effective against MRSA and innovative biofilm-resistant electrospun fibers, contributing to the global efforts to combat AMR.

Background: Expansion of OKF6/TERT-2 oral epithelial cells in vitro is important for studying the molecular biology of disease and pathology affecting the oral cavity. Keratinocyte Serum-Free Medium (KSFM) is the medium of choice for this cell line. This study compares three media for OKF6/TERT-2 cultures: KSFM, Dulbecco’s Modified Eagle Medium/Nutrient Mixture of Hams F-12 (DMEM/F12) and a composite medium comprised of DMEM/F-12 and KSFM (1:1 v/v), referred as DFK. The toxicological effects of electronic cigarette liquids (E-liquids) on OKF6/TERT-2 cells cultured in these media were also compared. Methods: Cells were cultured in KSFM, DMEM/F12 or DFK and cellular morphology, growth, wound healing and gene expression of mucins and tight junctions were evaluated. Additionally, cytotoxicity was determined after E-liquid exposures. Results: Switching from KSFM to DMEM/F12 or DFK 24-hours post-seeding leads to typical cellular morphologies, and these cultures reach confluency faster than those in KSFM. Wound-healing recovery occurred fastest in DFK. Except for claudin-1, there is no difference in expression of the other genes tested. Additionally, E-liquid cytotoxicity appears to be amplified in DFK cultures. Conclusions: DMEM/F12 and DFK are alternative media for OKF6/TERT-2 cell culture to study molecular biology of disease and pathology, provided cells are initially seeded in KSFM.

The capability of radially polymerized bio-dendrimers and hyperbranched polymers for medical applications is well established. Among them, perhaps the most important are those that involve interactions with the regenerative mechanisms of cells. Dendritic polymers due to their distinctive architecture may play a multitude of roles such as protein biomimicry (collagen, elastin, hydroxy apatite production), gene and drug delivery (cell differentiation, antimicrobial protection), surface chemistry and charge modulation (adhesion to cells and tissues), polymer cross-linking (eye, skin and internal organ wound healing). The review highlights all the different categories of hard and soft tissues that may be remediated with their contribution. The reader will be also exposed to the incorporation methods to established biomaterials such as scaffolds, the functionalization strategies, and the synthetic paths for the assembly from biocompatible building blocks and natural metabolites.

So far, poly(L-lactic acid), PLLA, nanosheets proved to be promising for wound healing. Such biodegradable materials are easy-to-prepare, bio-friendly, cost-effective, simple to apply and were shown to protect burn wounds and facilitate their healing. At the same time, certain metal ions are known to be essential for wound healing, which is why this study was motivated by the idea of incorporating PLLA nanosheets with Zn2+ ion containing nanoparticles. Upon being applied on wound, such polymer nanosheets should release Zn2+ ions, which is expected to improve wound healing. The work thus focused on preparing PLLA nanosheets embedded with several kinds of Zn-containing nanoparticles, their characterization and ion-release behavior. ZnCl2 and ZnO nanoparticles were chosen as model particles with different solubility in water, both types showing similar ion release dynamics in liquid medium with pH around 7.4.

Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of main biological processes in fabrication and construction of supramolecular hydrogel networks required for biomedical applications. The enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most of cases, structure and substrates of hydrogels are adjusted by enzyme catalysis due to the chemo-, regio- and stereo-selectivity of enzymes. Hydrogels processed by using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules and drugs in biomedical applications. A novel class of enzyme-mediated crosslinking hydrogels mimics the extracellular matrices by displaying unique physicochemical properties and functionalities like water-retention capacity, drug loading ability, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-healing ability, shape memory ability. In recent years, many enzymatic systems investigated hydrogel cross-linking. Results of biocompatible hydrogel products show that these mechanisms of crosslinking can fulfill requirements for variety of biomedical applications including tissue engineering, wound healing and drug delivery.

Hydrogels are used for various biomedical applications due to their biocompatibility, capacity to mimic the extracellular matrix, and ability to encapsulate and deliver cells and therapeutics. However, traditional hydrogels have a few shortcomings, especially regarding their physical properties, thereby limiting their broad applicability. Recently, researchers have investigated the incorporation of nanoparticles (NPs) into hydrogels to improve and add to the physical and biochemical properties of hydrogels. This brief review focuses on papers that describe the use of nanoparticles to improve more than one property of hydrogels. Such multifunctional hydrogel nanocomposites have enhanced potential for various applications, including tissue engineering, drug delivery, wound healing, bioprinting and biowearable devices.

Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodeling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

Developing novel wound dressings containing medicinal plant extracts can have several potential benefits, including improving the therapeutic value of the dressings and reducing the cost of producing wound dressings. In this study, we prepared foam dressing containing Eclipta prostrata leaf extract and gelatin (Eclipta prostrata dressing). Chemical composition was verified using Fourier transform infrared spectroscopy (FTIR), and pore structure was obtained by scanning electron microscopy (SEM). The physical properties, including absorption and dehydration properties, were also evaluated. The chemical properties were measured to determine the pH environment after being submerged with Eclipta prostrata dressings. The results revealed that the Eclipta prostrata dressing had a pore structure with an appropriate pore size (313.25 ± 76.51 µm and 383.26 ± 64.45 µm for the Eclipta prostrata A and Eclipta prostrata B dressings, respectively). The Eclipta prostrata B dressing was more consistent porosity, resulting in a higher absorption capacity and faster dehydration rate. According to physical properties, the Eclipta prostrata B dressing is best used on low-exuding wounds. Furthermore, the Eclipta prostrata A and B dressings make a slightly acidic environment. Therefore, our foam dressing will not interfere wound healing process.

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against Methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

Background: Skin and soft tissue infections (SSTI) are common presentations to the emergency department. However, this is less common after contact with contaminated water, both salt or fresh. This review presents the diagnosis and the management of water-related soft tissue sepsis in this vulnerable and difficult to treat subgroup of necrotizing soft tissue sepsis. Methods: A summative literature overview regarding bacterial and fungal SSTI after contact with contaminated water, with practical diagnostic and management aspects addressed. Results: The literature indicates that these remain difficult to treat wounds and organisms. An approach using appropriate diagnostic tools with both medical and surgical management strategies is provided. Conclusion: SSTI due to water contamination of wounds involve unusual organisms with unusual resistance patterns and require a nuanced and directed diagnostic approach with adaptation of the normal antibiotic or antifungal selection to achieve cure, along with aggressive debridement and wound care.

Chemical composition analysis of açaí extracts revealed higher levels of total polyphenol content in purple açaí samples for both commercial (4.3 – 44.7 gallic acid equivalents mg/g) and non-commercial samples (30.2 – 42.0 mg/g) compared to white (8.2 – 11.9 mg/g) and oil samples (0.8 – 4.6 mg/g). The major anthocyanin compounds found in purple açaí samples were cyanidin-3-glucoside and cyanidin-3-rutinoside with total concentrations in the range of 3.6 – 14.3 cyanidin-3-glucoside equivalents mg/g. The oligomeric proanthocyanidins were quantified in the range of 1.5 – 6.1 procyanidin B1 equivalents mg/g. Moreover, açaí presented significant levels of calcium, magnesium, manganese, iron, zinc and copper, essential minor and trace elements, in comparison with other berries. All of the açaí extracts at 50 μg/mL potently inhibited the release of reactive oxygen species in lipopolysaccharide-stimulated RAW 264.7 macrophage cells, but none inhibited the release of nitric oxide. Furthermore, all the açaí samples demonstrated potential as wound healing agents due to the high levels of migration activity in human fibroblast cells.

1) Introduction: Negative pressure wound therapy (NPWT) is a frequently applied open abdomen (OA) treatment. There are only a few experimental data supporting this method and describing the optimal settings and pressure distribution in the abdominal cavity during this procedure. The aim of our study was to evaluate pressure values at different points of the abdominal cavity during NPWT in experimental abdominal compartment syndrome (ACS) animal model. 2) Methods: In this study (permission Nr. 13/2014/UDCAR) 27 Hungahib pigs (15.4- 20.2 kg) were operated. ACS was generated by implanting a plastic bag in the abdomen through mini-laparotomy and filled with 2100- 3300 ml saline solution (37 C°) to an intraabdominal pressure (IAP) of 30 mmHg. After 3 hours, NPWT (Vivano Med ® Abdominal Kit, Paul Hartmann AG, Germany) or Bogota bag was applied. NPWT group was divided into -50, -100 and 150 mmHg suction group. Pressure distribution to the abdominal cavity was monitored at 6 different points of the abdomen via a multichannel pressure monitoring system. 3) Results: The absolute pressure levels were significantly higher above than below the layer. The values of the pressure were similar in the midline than laterally. Amongst the bowels, the pressure values changed periodically between 0 and -12 mmHg which might be caused by the peristaltic movements. 4) Conclusions: The porcine model of the present study seems to be well applicable for investigating ACS and NPWT. It was possible to provide valuable for clinicians. The pressure was well distributed by the protective layer to the lateral parts of the abdomen and this phenomenon did not change considerably during the therapy.

This review describes the positive effects of growth hormone on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on the vascular endothelium improving its dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease inducing the generation of new collateral vessels able to bypass a major artery occlusion. We include some preliminary data from a trial in which GH or placebo is given to elder people suffering from critical limb ischemia, showing the effects of the hormone on plasma markers of inflammation, and stating that the administration of GH in short periods of time is safe and effective even in diabetic patients. We also analyze how Klotho may have strong relationships with GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH to repair the damaged tissue. Lastly, we show how GH induces wound healing by increasing the blood flow to the ischemic tissue. In summary, we postulate that short-time GH administration is useful for treating cardiovascular diseases.

Due to the still large number of patients diagnosed with pelvic neoplasms (colorectal, gynecological, and urological) in advanced stages right from the initial diagnosis, surgery represents the mainstay of treatment, often implying wide, eventually multi-organ resections in order to achieve negative surgical margins. Perineal wound morbidity, particularly in extralevator abominoperineal excision, leads to complications and local infection rates of up to 40%. Strategies to reduce postoperative wound complications are pursued to address this issue.The VRAM flap remains the gold standard for autologous reconstruction after pelvic oncological resection; it was initially designed for abdominal wall defects and later expanded for large pelvic tissue defects.The flap's application is based on its physical characteristics, including abundant tissue and a generous skin paddle, which effectively obliterates dead space after exenterations. The generous skin paddle offers good cosmetic and functional outcomes at the recipient site.This article describes the case of a patient histopathologically diagnosed with stage IIIA squamous cell carcinoma of the uterine cervix who received multimodal onco-surgical treatment. The surgical mainstay of this treatment is pelvic exenteration. Pelvic reconstruction after this major surgery was performed using a vertical flap with the rectus abdominis.

Wound infection is a common complication of chronic wounds. It can impair healing, which may not occur without external help. Antimicrobial dressings (AMDs) are a type of external help to infected chronic wounds. In this study, highly porous membranes made of only chitosan and containing the antiseptic polyhexanide (poly(hexamethylene biguanide); PHMB) were prepared by cryogelation, aiming to be used in AMDs. These membranes exhibited high water swelling capacity, fast water absorption and high water vapor transmission. The best drug loading method involved simultaneous loading by soaking in a PHMB solution and sterilization by autoclaving, resulting in sterilized, drug-loaded membranes. The drug release kinetics was comparable to that of a commercial PHMB-releasing AMD assayed under the same conditions. These membranes exhibited high antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are bacterial species commonly found in infected wounds, and blood clotting activity. The obtained results suggest that these membranes may be suitable for use in the development of AMDs.

Biosurfactants (BSs) are microbial compounds that have emerged as potential alternatives to chemical surfactants due to their multifunctional properties, sustainability, and biodegradability. Owing to their amphipathic nature and distinctive structural arrangement, biosurfactants exhibit a range of physicochemical properties, including excellent surface activity, efficient critical micelle concentration, humectant properties, foaming and cleaning abilities and the capacity to form microemulsions. Furthermore, numerous biosurfactants display additional biological characteristics, such as antibacterial, antifungal, and antiviral effects, antioxidant, anticancer, and immunomodulatory activities. Over the past two decades, numerous studies have explored their potential applications, including pharmaceuticals, cosmetics, antimicrobial and antibiofilm agents, wound healing, anticancer treatments, immune system modulators and drug/gene carriers. These applications are particularly important in addressing challenges such as antimicrobial resistance and biofilm formation in clinical, hygiene, and therapeutic settings. They can also serve as coating agents for surfaces, enabling antiadhesive, suppression, or eradication strategies. Not least importantly, biosurfactants have shown compatibility with various drug formulations, including nanoparticles, liposomes, micro and nanoemulsions, and hydrogels, improving drug solubility, stability, and bioavailability and enabling targeted and controlled drug release. These qualities make biosurfactants promising candidates for the development of next-generation antimicrobial, antibiofilm, anticancer, wound healing, immunomodulating, drug or gene delivery agents, as well as adjuvants to other antibiotics. Analyzing recent literature, this review aims to provide insights into the present understanding, highlight emerging trends, identify promising directions and advancements in the utilization of biosurfactants within the pharmaceutical and biomedical fields.

Biomass and biowaste valorisation is of major interest nowadays because of the spirit of circular economy and of the neutral environmental fingerprint global target. In the current project chondroitin sulphate (ChS) was incorporated with the crustaceous’ and shrimp’s byproduct chitosan (Chi) and the fish industry byproduct gelatine (FG) to obtain dense hydrogel membranes. Glycerol (Gly) was utilized to avoid brittleness. The formation of the hydrogel membranes is attributed to secondary interactions between the natural polymers and the plasticizer. The prepared hydrogel membranes were characterized by Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The surface morphology of the membranes was examined using scanning electron microscopy (SEM). Dynamic mechanical analysis (DMA) and tensile tests were also performed to evaluate the mechanical response of the membranes. The samples were also evaluated for membrane wettability, degradation rate and water vapor transmission rate (WVTR). Finally, in vitro endothelial cell attachment on the membrane were addressed. The overall results of the study indicate that the hydrogel membranes could be appropriate for external application in wound healing applications as dressings.

Despite being under development for decades, RNA therapeutics have only recently emerged as viable platform technologies. The COVID-19 mRNA vaccines have demonstrated the promise and power of the platform technology. In response, novel RNA drugs are entering clinical trials at an accelerating rate. As the skin is the largest and most accessible organ, it has always been a preferred target for drug discovery. This holds true for RNA therapies as well, and multiple candidate RNA-based drugs are currently in development for an array of skin conditions. In this mini review, we catalog the RNA therapies currently in clinical trials for different dermatological diseases. We summarize the main types of RNA-related drugs and use examples of drugs currently in development to illustrate their key mechanism of action.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

The indole-3-pyruvic acid pathway is the major route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of L-tryptophan via indole-3-pyruvic acid into indole-3-acetic acid (IAA). It has been described that locally produced jasmonic acid (JA) in response to mechanical wounding, triggers de novo-formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of YUC8 and YUC9 gene expression depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. In addition, transactivation assays provided experimental evidence for the binding of the MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in those of the other YUCCA genes. Moreover, we clearly demonstrate that YUC8ox and YUC9ox overexpressing plants show less damage after spider mite infestation, thereby underlining a role of auxin in plant responses toward biotic stress cues.

Background: In 2014 the World Health Organization (WHO) warned of an emerging world-wide crisis of antibiotic resistant microorganisms. In response, government and professional organizations recommended that health care systems adopt antimicrobial stewardship programs (ASPs). In the United States, the Centers for Medicare Services (CMS) mandated antimicrobial stewardship in the hospital inpatient setting. Effective January 1, 2020, the Joint Commission required ambulatory centers that prescribe antibiotics, such as wound centers, to institute an ASP. Chronic wounds often remain open for months, during which time patients may receive multiple courses of antibiotics and numerous antimicrobial topical treatments. The wound clinician plays an integral role in reducing antimicrobial resistance in the outpatient setting: antibiotics prescribed for skin and soft tissue infections are among the most common in an outpatient setting. One of the most challenging aspects of antimicrobial stewardship in treating chronic wounds is the inaccuracy of bacterial and infection diagnosis. Methods: Joint Commission lists five elements of performance (EP): (1) Identifying an antimicrobial stewardship leader, (2) establishing an annual antimicrobial stewardship goal, (3) implementing evidence-based practice guidelines related to the antimicrobial stewardship goal, (4) providing clinical staff with educational resources related to the antimicrobial stewardship goal, and (5) collecting, analyzing, and reporting data related to the antimicrobial stewardship goal. This article focuses on choosing and implementing an evidence-based ASP goal for 2020. Discussion: Clinical trials have demonstrated the ability of fluorescence imaging (MLiX) to detect clinically significant levels of bacteria in chronic wounds. Combined with clinical examination of signs and symptoms of infection, the MLiX procedure improves the clinician’s ability to diagnose infection and can guide antimicrobial use. In order to satisfy the elements of performance, the MLiX procedure was incorporated into the annual ASP goal for several wound care centers. Clinicians were educated on the fluorescence imaging device and guidelines were instituted. Collection of antimicrobial utilization data is underway.

Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges in size from one to one hundred nanometers. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism that it is tested on, all have a large determining factor on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signaling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress, as well as the effects of nanosilver on the responses to such stresses, are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis, as well as other pathway alterations are examined in this review.

Hidradenitis suppurativa and Langerhans cell histiocytosis are rare disorders that can reveal similar clinical manifestations, making differential diagnosis difficult. A definitive diagnosis requires biopsy and histological confirmation in suspicious cases. The complex pathophysiology of these diseases has still not been understood, therefore the treatment is still a challenge for physicians. It is seen with predilection in the intertriginous areas of the body, predominantly in the axillary region, rarely requiring a surgical procedure. However perineal, perianal, and gluteal HS usually necessitates some form of surgical treatment. Langerhans cell histiocytosis (histiocytosis X) is a very rare systemic disease manifested by clonal cell proliferation of histiocytic-dendritic nature, with pseudonodular manifestation that deeply infiltrates the hypodermis and ulcerates the epidermis on the surface. Langerhans cells are dendritic, antigen-presenting cells localized in the suprabasal regions of the squamous epithelium of the skin and mucous membranes, which help regulate the immune system. In this report, we present our experience with extensive gluteal, perineal, and perianal hidradenitis suppurativa and Langerhans cell histiocytosis cases, including our treatment methods and outcomes.

The connective tissue mast cell (MC), a sentinel tissue-residing secretory immune cell, is preserved in all vertebrate classes since approximately 500 million years. No physiological role of the MCs has yet been established. Considering the power of natural selection of cells during evolution, it is likely that the MCs exert essential yet unidentified life-promoting actions. All vertebrates feature a circulatory system, and the MCs interact readily with the vasculature. It is notable that embryonic MC progenitors are generated from endothelial cells. The MC hosts many surface receptors enabling its activation by a vast variety of potentially harmful exogenous and endogenous molecules, and by reproductive hormones in the female sex organs. Activated MCs release a unique composition of pre-formed and newly synthesized bioactive molecules, like heparin, histamine, serotonin, proteolytic enzymes, cytokines, chemokines, and growth factors. MCs play important roles in immune responses, tissue remodeling, cell proliferation, angiogenesis, inflammation, wound healing, tissue homeostasis, health, and reproduction. As recently suggested, MCs enable perpetuation of the vertebrates because of key effects—spanning generations—in ovulation and pregnancy, as in life-preserving activities in inflammation and wound healing from birth till reproductive age, thus creating a permanent life-sustaining loop. Here, we present recent advances that further indicate that the MC is a specific life-supporting and progeny-safeguarding cell

Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph­angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. The activating cleavage of VEGF-C is mediated by at least five different proteases: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the "mature" growth factors, which differ in affinity and receptor activation potential. The “default” VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by different proteases. During embryonic development, ADAMTS3 activates VEGF-C. In contrast, thrombin and plasmin likely activate VEGF-C/-D during tissue injury-induced lymphangiogenesis, and PSA and cathepsin D perhaps during tumor-associated pathological lymphangio­genesis. Additionally, cathepsin D from saliva might activate latent VEGF-C/-D upon wound licking, thereby accelerating healing. Similar to tyrosine kinase receptors and VEGFs themselves, these activating proteases could be targeted to modulate angiogenesis and lymphangiogenesis in relevant diseases.

The goal of this study was to determine the relative susceptibility of four common equine wound pathogens to ten different types of antimicrobial agents based on minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Additionally, to describe the comparison of bactericidal activity of medical grade Manuka honey, local honey, and commercial, food-grade honey to other commonly used wound dressings. The objective is to provide veterinary practitioners with comparative data on the use of a variety of antimicrobial dressings for inhibiting growth of common wound bacteria. MIC and MBC for Manuka, store, and local honeys were comparable to those of sterile gauze, sugar, and hypertonic saline. Across bacterial species, local honey proved to have more bactericidal activity when compared to Manuka and commercial, food-grade honey. The MIC and MBC for PHMB gauze and foam was consistently at a higher dilution compared to the other antimicrobials. The majority of antimicrobials exhibited stronger inhibitory and bactericidal activity against a Streptococcus zooepidemicus isolate obtained from a wound compared to other bacteria that were ATCC lab acclimated. Additional research for in-vivo applications needs to be done to see whether differences exist in effective wound management.