Normal Skin Research Articles

B-350 The application of MALDI-TOF imaging to biomarker discovery in a mouse model of papillomavirus associated tumorigenesis

Abstract Background Human papillomavirus (HPV) can cause infection and dysplasia in cutaneous epithelium of immunodeficient patients. An animal model has been developed to study HPV-associated tumorigenesis using Nude mouse (Foxn1nu) and mouse papillomavirus (MmuPV1). This study applies MALDI-TOF imaging to compare the expression pattern of small molecules between viral-infected dysplastic mouse skin and mock-infected control tissue. Three sets of molecules showing distinct patterns are identified in correlation with the upregulation of an enzyme in related biosynthetic pathway. Methods Nude mice were wounded on tail and inoculated with MmPV1 suspension (1×109 viral DNA genomes per infected site) or PBS 24 hours later for treatment and control group, respectively. Tail skins were harvested 4 weeks post-infection and processed for cryosectioning. Tissue sections were analyzed using timsTOF flex (Bruker) under negative ion mode with 9-aminoacridine as the matrix. Viral infection (MmuPV1-L1 antigen) and enzyme expression (3'-phosphoadenosine 5'-phosphosulfate synthetase 1, PAPSS1) were assessed by immunofluorescence on adjacent sections. Results Three peaks demonstrated distinct distribution patterns in mouse skin. One peak at m/Z = 465 was identified as cholesterol sulfate (CS) by tandem MS and comparing with the standard. CS was enriched in keratinocytes, hair follicles, and blood vessels in normal skins, and it increased in dysplastic skins with enhanced angiogenesis. The combined peaks at m/Z = 327 & 329 were tentatively identified as docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). These long chain polyunsaturated fatty acids (LC-PUFAs) were present in the dermis as foci partially co-localized with CS, and they also increased in virus-infected skins. The peak at m/Z = 426 may represent a combination of ADP and APS. Although these two isobars cannot be separated by tandem MS, APS was revealed by the presence of sulfur isotopes at expected natural abundance (34S and 32S). They were present at a low level in the epidermis of normal skins but significantly increased after virus infection. APS and ADP were closely associated with the proliferating cells, and the signal intensity also increased with the degree of tissue dysplasia. As a single factor, APS & ADP demonstrated a fair differential power for MmuPV1-induced dysplastic skin and normal control (AUC of ROC curve = 0.75). The bifunctional enzyme PAPSS1 catalyzes the conversion of ATP to 3’-phosphonato-5’-adenyl sulfate (PAPS) via APS as an intermediate. Interestingly, immunofluorescence showed the expression of PAPSS1 also increased significantly with the severity of tissue dysplasia and MmuPV1 infection. Conclusions MALDI-TOF imaging reveals three sets of molecules with distinct patterns in mouse skin, and their levels are increased during MmuPV1-induced epithelium dysplasia. As a precursor of the common sulfate donor (PAPS), increased APS and ADP in the epidermis of virus-infected skins indicate an upregulation of sulfation pathway and adenine metabolism. This finding is supported by enhanced expression of enzyme PAPSS1 and an increased sulfation reaction product, CS. In addition, DHA and DPA are also increased in the dermis of virus-infected skins, implying a disturbance in LC-PUFA metabolism. This study demonstrates combined use of MALDI-TOF imaging and immunostaining in the search of novel biomarkers of HPV-associated tumorigenesis.

Overexpression of the key metabolic protein Carnitine Palmitoyl Transferase 1A (CPT1A) in equine sarcoid

The equine sarcoid is the most common skin neoplasia of fibroblastic origin in horses, characterized by an excessive accumulation of extracellular matrix produced by sarcoid fibroblasts under hypoxic condition. Neoplastic cells can adapt to hypoxia by using alternative energy sources, particularly those that arise from fatty acid oxidation (FAO). The Carnitine Palmitoyl Transferase 1A (CPT1A) belongs to Carnitine System (CS) and promotes the entrance of fatty acids into the mitochondria for β-oxidation. In this study, CPT1A expression was comparatively addressed in 25 equine sarcoids and 5 normal skin samples using immunohistochemistry (IHC). Specificity of CPT1A antibody was validated by Western Blotting (WB). In normal skin samples IHC staining was weak and mainly confined to basal epidermis and few dermal fibroblasts. Sarcoid fibroblast exhibited a strong cytoplasmic and nuclear signal in 60% of the tumor samples. Cytoplasmic CPT1A expression in sarcoid fibroblasts indicates that the protein is actively involved in metabolic reprogramming processes. Nuclear CPT1A expression suggests that the protein may also be involved in the regulation of neoplastic proliferation.

Comparison of Normal Human Skin and Hypertrophic Scar Tissue Samples of Different Ages, Locations, and Stages of Maturity.

Scars disrupt the normal structure and function of the skin. The primary goal of plastic surgery is to prevent and reduce scarring. Therefore, we aimed to establish a comparison scheme between normal skin (NS) tissues of different ages and locations; hypertrophic scars (HTS) of different ages, locations, and maturities; and NS and HTS tissues to provide evidence on scar severity for improving treatment evaluation. Various methods including histology, immunohistochemistry, and immunofluorescence were employed to compare the general appearance, macrophage infiltration, fibroblast activity, degree of angiogenesis, and collagen fiber type and arrangement in human-sourced NS and HTS tissues of different ages, locations, and maturities in seven patients (three with NS and four with HTS) from the Department of Burn and Plastic Surgery of the Shandong Provincial Hospital from January 2019 to December 2020. The thicknesses of the epidermis and dermis of NS tissues varied with age and location. The epidermis of the upper arms, face, and upper eyelids of NS tissues sequentially thickened, whereas the dermis was sequentially thinner. Several glandular structures were identified in the upper eyelids but rarely in the face and upper arms. Histological changes in HTS tissue of different ages, locations, and maturity occur as scar formation time is prolonged, accompanied by increased CD86 levels and fibrosis. As the scar matured, connexin and VEGFR2 expression decreased, indicating reduced inflammation, fibroblast activity, and angiogenesis. The comparison between NS and HTS tissue also revealed significant differences; the positive expression of VEGFR2 and total collagen in HTS tissue was higher than that in NS tissue. We discovered significant differences among NS, HTS, and NS and HTS tissues of different ages, locations, and maturities. Further, this study may provide a basis for clarifying the treatment effect of different methods for HTS compared with those for NS, efficiently individualizing patients' treatment plans and ultimately shortening the scar treatment process.

Enhanced Anticancer and Biological Activities of Environmentally Friendly Ni/Cu-ZnO Solid Solution Nanoparticles

The study investigates the impact of incorporating Ni and Cu into the lattice of ZnO nanoparticles (NPs) to enhance their anticancer and antioxidant properties. Characterization techniques including pXRD, FTIR, UV-visible absorption spectroscopy, FESEM, and EDAX confirm the successful synthesis and structural modifications of Ni/Cu-ZnO NPs. Anticancer activity against breast cancer (MDA) and normal skin (BHK-21) cells reveals dose-dependent cytotoxicity, with Ni/Cu-ZnO NPs exhibiting higher efficacy against MDA cells while being less harmful to BHK-21 cells. Morphological studies corroborate these findings. Additionally, antioxidant assays using TAC, FRAP, and DPPH assay demonstrate the superior antioxidant activity of Ni/Cu-ZnO NPs matched to pure ZnO. Overall, the synergistic effect of Ni and Cu incorporation leads to improved therapeutic potential, making Ni/Cu-ZnO NPs promising candidates for cancer therapy and antioxidant applications.Molecular docking recreations were performed using Auto Dock Vina software to gain more insights and validate the observed biological activities of un-doped ZnO and bi-metal doped ZnO NPs, we investigated the interaction and binding affinities of pure ZnO and bimetallic metal co-doped ZnO for their antioxidant and anticancer studies. Ni/Cu-ZnO have shown good antioxidants and exhibited remarkable anticancer activities.

Bovine papillomavirus gene expression and inflammatory pathway activation vary between equine sarcoid tumour subtypes

Equine sarcoids are common non-metastasising skin tumours in horses, associated with bovine papillomavirus (BPV) infection. Six subtypes are recognised (occult, verrucose, nodular, fibroblastic, mixed and malevolent lesions), with variable clinical behaviour. The pathophysiology underlying varying tumour phenotype is poorly understood, and previous data on associations with viral load have been conflicting. To better understand this clinical variation, we investigated associations between tumour subtype and viral load, viral early protein gene expression, and expression of 10 host genes by quantitative polymerase chain reaction in 27 sarcoids and 5 normal skin samples. Viral DNA copy number did not differ between subtypes but was significantly higher in animals with fewer tumours. Expression of BPV E2 and E6 was higher in occult lesions compared to fibroblastic or nodular lesions, while E5 expression was higher in previously-treated lesions. Of the host genes, only IL6 and IL1B differed between subtypes, with higher expression in fibroblastic lesions, while IL10 and CCL5 were elevated compared to skin in all lesion types, and elevations in TNF and TGFB1 were significant for occult lesions only. Expression of TLR9, ATR, VEGFA and PTGS2 in sarcoids was not significantly different from normal skin, suggesting differences between BPV and human papillomavirus tumorigenesis. Results for BPV viral load and gene expression differed from previous reports and are insufficient to explain the spectrum of tumour phenotypes. Activation of both pro-inflammatory and anti-inflammatory immune pathways in sarcoids could influence tumour growth and effective immune responses, and the contribution of specific infiltrating immune cells requires further investigation.

Dermal Regeneration Template Generated Skin Can Be Raised as A Flap: A New Dimension in Aesthetic Restoration

AbstractChildhood scars can lead to hideous aesthetic and functional deformities in young adults, which can be particularly distressing when involving the face and the breast in a female. Aesthetic restoration requires replacement of the whole or a part of the scarred skin by soft, pliable, and texture-matching skin, which nearly always is in short supply. Dermal regeneration templates (DRTs) can help in skin regeneration that is almost always aesthetically superior to most flaps. Aesthetic demands at the time of final restoration may require the regenerated skin to be moved as a local flap. As regenerated skin from dermal templates is known to match the vascularity of normal native skin, raising it as a flap should follow logically. This, however, has never been attempted to the best of our knowledge after a thorough literature search. We report a case of successfully using DRT-generated skin raised as a flap for aesthetic reconstruction of a postburn scarred breast in a young female. This adds a whole new dimension to the use of DRTs and points to a new field of research in scar management and aesthetic restoration.

RNAs m6A modification facilitates UVB-induced photoaging

RNA N6-methylation (m6A) modification is common in eukaryotic mRNA and has been linked to various physiological disorders, including UVB-induced photoaging. To identify biological differences among photoaging. Three pairs of normal and photoaged skin tissues were collected for m6A RNA sequencing assay. Transcriptome profiles showed differential m6A methylation modifications in 1365 mRNAs in photoaging skin tissues. Pathway analysis revealed the involvement of cellular stress response and regulation of cell cycle G2/M phase transition in m6A-mRNAs. Further experiments validated the differential expression of m6A methyltransferases (METTL3 and METTL14) and hypermethylation modification in mRNAs (CENPE, PPM1B and TPM1). In vitro studies demonstrated that increased METTL3 and METTL14 levels promoted m6A methylation of CENPE, PPM1B and TPM1 in UVB-induced photoaging cells, and further experiments on mice showed that downregulation of METTL3 and METTL14 reduced m6A modifications in CENPE, PPM1B and TPM1, leading to the delayed appearance of photoaging phenotypes, suggesting that these genes could serve as potential therapeutic targets for treating photoaging. Our study characterized key transcriptome changes in photoaging and identified the role of METTL3 and METTL14 in mediating m6A modification, resulting in the upregulation of CENPE, PPM1B and TPM1 expression, which may be crucial in UVB-induced photoaging.

Exploring Potential Biomarkers and Molecular Mechanisms of Cutaneous Squamous Cell Carcinoma Based on Bioinformatics.

Cutaneous squamous cell carcinoma (cSCC) ranks as the second most common malignancy in clinical practice and poses a significant threat to public health due to its high malignancy. In this study, we aimed to explore potential biomarkers and molecular mechanisms of cSCC. Differentially expressed genes (DEGs) from GSE66359 and GSE117247 datasets were identified using R software. We conducted enrichment analyses and screened hub genes through protein-protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA). To assess the diagnostic performance of these genes, we generated ROC curves using both internal and external datasets (GSE45164) and validated the expression levels of these genes in cSCC tissues through immunohistochemistry. Subsequently, we predicted the target miRNAs and lncRNAs for hub genes using online databases and constructed competing endogenous RNA (ceRNA) networks. In total, we identified 505 upregulated DEGs and 522 downregulated DEGs. Through PPI and WGCNA analyses, we identified four hub genes exhibiting robust diagnostic performance in internal and external datasets (AUC > 0.9) and selected three previously unreported genes for further analysis. Immunohistochemistry demonstrated significantly elevated CCNA2, CCNB2, and UBE2C expression in cSCC tissues compared to normal skin tissues. Finally, we constructed three ceRNA networks, namely NEAT1/H19-hsa-miR-148a-3p-CCNA2 and NEAT1-hsa-miR-140-3p-UBE2C. In conclusion, we have identified CCNA2, CCNB2, and UBE2C as novel biomarkers for cSCC, and the NEAT1/H19-hsa-miR-148a-3p-CCNA2 and NEAT1-hsa-miR-140-3p-UBE2C ceRNA networks may represent molecular mechanisms under-lying cSCC progression. The findings of this study offer new diagnostic and therapeutic options for cSCC patients.

Periostin regulates the activity of keloid fibroblasts by activating the JAK/STAT signaling pathway

A keloid is secondary to skin trauma or has spontaneously manifested as an overgrowth and occurs when the skin heals abnormally after an injury. The main pathological manifestations are abnormal proliferation of keloid fibroblasts (KEL-FIB). This study researched periostin (POSTN) on keloid fibroblasts (KEL-FIB) and the associated mechanism, aiming to provide a reference for the targeted therapy of keloid. We got tissues from Second People’s Hospital of Guangxi Zhuang Autonomous Region between June 2022 and March 2023. POSTN expression was increased in keloid skin tissue and KEL-FIB than normal skin tissue and normal fibroblasts. We collected and inoculated KEL-FIB cells, transfection of si-NC (Silencing of POSTN negative control), si-POSTN (Silencing of POSTN), pcDNA-NC (Overexpression of POSTN negative control), and POSTN (Overexpression of POSTN) (Thermo Fisher Scientific) used Lipofectamine 2000 transfection reagent. Wound closure, cell proliferation viability, migrated cell numbers, and POSTN, p-JAK2, p-STAT3 protein levels were reduced in the si-POSTN group. Wound closure, cell proliferation viability, migrated cell numbers, and POSTN, p-JAK2, p-STAT3 protein levels were elevated in the POSTN group. POSTN protein levels did not changed and wound closure, cell proliferation viability, migrated cell numbers, were reduced in the POSTN+S-Ruxolitinib group. The study results indicated that POSTN promotes cell migration and proliferation by activating the JAK/STAT pathway, promoting KEL-FIB development.

Novel multi-spectral short-wave infrared imaging for assessment of human burn wound depth.

Burn depth determination is critical for patient care but is currently lacking accuracy. Recent animal studies showed that Short Wave Infrared (SWIR) imaging can distinguish between superficial and deep burns. This is a first human study correlating reflectance of multiple SWIR bands using a SWIR assessment tool (SWAT) with burn depth classifications by surgeons and histology. Burns and adjacent normal skin in 11 patients with thermal injuries were imaged with visual and narrow bands centred at 1200, 1650, 1940 and 2250 nm and biopsies were taken from select areas. Reflectance intensities for each band in 273 regions of interest (ROI) were divided by the normal skin reflectance and combined into three Reflectance Indices (RIs). In addition, burns in ROIs and biopsies were classified by five surgeons and three pathologists, respectively, as superficial partial, deep partial, or full thickness. Results show that for burn depth increase classified by the surgeons, reflectance increased at 1200 and 2250, decreased at 1940, and didn't change at 1650 nm. In contrast, all three RIs increase with burn depth and predict the deep and full depths ROIs representing operable regions (Area Under Curve >0.6507, p < 0.0001). Pathologists' classification matched surgeons' classification of burn category only in eight of 21 biopsies (38.1%), but reflectance at all bands and one RI for all deep partial and full thickness biopsies were larger than in non-biopsy normal and superficial partial thickness ROIs (p < 0.0118). In conclusion, multi-spectral imaging with a new SWAT is a promising approach for evaluation of burn wound depth.

PH‐responsive bionanocomposite pectin grafted with dimethylaminoethyl methacrylate and acrylic acid copolymer along with silver nanoparticles for breast cancer drug delivery

AbstractIn this study, we developed a pH‐responsive hydrogel membrane composed of pectin, dimethylaminoethyl methacrylate (DMAEMA), and acrylic acid (AA) through a free radical‐triggered graft copolymerization method. Freshly formed silver nanoparticles (AgNPs) produced from the reduction reaction were embedded in the produced hydrogel. Pectin‐grafted dimethylaminoethyl methacrylate and acrylic acid copolymer [poly (DMAEMA‐co‐AA)‐g‐pectin] and its bionanocomposite with AgNPs were confirmed by Fourier‐transform infrared spectroscopy (FT‐IR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The swelling behavior of poly (DMAEMA‐co‐AA)‐g‐pectin in solutions with diverse pH values was assessed. For use as a controlled drug delivery agent, the hydrogel was loaded with 5‐fluorouracil (5‐FU). The incorporation of AgNPs had a great impact on the entrapment efficiency of 5‐FU. At pH 7.4, nearly 48% of the 5‐FU was released in vitro from the polymeric nanocomposite within 24 h. Moreover, poly (DMAEMA‐co‐AA)‐g‐pectin and poly (DMAEMA‐co‐AA)‐g‐pectin/AgNPs presented high cytocompatibility toward normal skin fibroblast cells (BJ1), and the drug delivery system strongly inhibited human Caucasian breast adenocarcinoma cells (MCF‐7). These results demonstrated that these poly (DMAEMA‐co‐AA)‐g‐pectin/AgNPs are an excellent candidate for use in anticancer drug delivery systems.Highlights Free radical polymerization of nanocomposites incorporated with nanoparticles. Nanoparticles improve the bionanocomposites' drug loading. The developed bionanocomposites exhibit control drug release. The novel bionanocomposites acts as an excellent anticancer drug carrier.

A novel model of post-burn hypertrophic scarring in rat tail with a high success rate and simple methodology

BackgroundHypertrophic scars present a serious concern after surgeries and trauma, particularly with the highest risk following burn injury. The current modeling methods usually involve relatively complicated surgical operations and special equipment, and have unstable reproducibility and reliability. This study aimed to establish a simple and reliable model of post-burn hypertrophic scarring in the rat tail. MethodsWet gauze saturated with hot water (94–98 °C) was applied to the dorsal side of the rat tail for varying durations to induce burn injury. Wounds were left exposed until completely healed, and the optimal duration for scalding treatment was determined based on gross examination. Thereafter, the optimal scalding duration was used again to evaluate scar formation over time, which was tracked through hematoxylin-eosin (HE) and Masson staining, immunohistochemistry of scar-related proteins and number/distribution of vascular endothelial cells, and picrosirius red staining to measure the quantities and proportion of type I and III collagen. ResultsThe scalding duration which led to optimal post-burn scarring was 15 s, with an overall success rate of 87.5 %. Complete healing of the wound occurred after roughly 30 days, leading to the formation of scars grossly red in appearance, tough to the touch and raised compared to the surrounding skin. Microscopically, the epidermis and dermis of the scar were significantly thicker than normal rat tail skin, and the dermis of scar contained a large number of disorganized bundles of fine filamentous collagen. We also observed a significant increase in the number of TGF-β1-positive cells and capillaries in the dermis (p < 0.05). Picrosirius red staining showed that compared to type III collagen, the expression of type I collagen was more dominant in scar tissue, and was more finely distributed than in normal rat tail skin. ConclusionWe successfully established a model for post-burn hypertrophic scarring, utilizing reliable and simple techniques and materials, which could simulate the biological characteristics of post-burn scarring. Our innovative model has the potential to facilitate the study of post-burn wound healing and scar formation.

A miniaturized dual band terahertz metamaterial based absorber as a biosensor for non-melanoma skin cancer diognostic

Early diagnosis of Non-melanoma skin cancers (NMSCs) is most important for successful treatment of the disease.The detection of NMSCs involves visual inspection or invasive method of detection by skin biopsy. Recently, terahertz spectroscopy has come into limelight for detection of biomarkers in low terahertz (THz) region in between 0.1 – 10 THz which will be in resonance with the biomolecules. This work entails in designing a microscale THz metamaterial absorber for discriminating the attributes between Non-melanoma skin cancerous skin and normal skin. The proposed absorber is composed of space filling curved aluminum layer over a polymide substrate. The absorber culminates its absorbance peak of 99.8 % at 0.503 THz and 99.5 % at 1.076 THz, revealing its dual band trait. Moreover, variation of refractive index of the medium from 1.3 to 1.4 shows shift in absorption peak with a sensitivity of 95.76 GHz/RIU and 100 GHz/RIU for first and second band respectively.

Modulation of Melanocyte in Melasma Patients After Picosecond Laser Treatment.

Melasma is a therapeutically challenging hyperpigmented skin condition. Currently, there is a lack of invivo observation regarding changes in melanin and dendritic melanocytes after laser treatment. To investigate alterations in melanin and melanocytes in melasma before and after laser treatment using optical coherence tomography (OCT). Eight female melasma patients were enrolled in Taiwan. Based on the baseline OCT scans, the patients were categorized into either epidermal-type or mixed-type melasma and were assigned different treatment protocols accordingly. Sequential OCT images were collected from melasma lesions and normal skin at baseline, Week 4 and Week 8. After 8 weeks of laser treatment, the mean Melasma Area Severity Index (MASI) score improved from 10.92 to 6.30. Results from OCT showed no significant changes in the normalized density, area, or intensity of melanin in both lesional and normal skin. At baseline, the mean length of dendritic melanocytes in the affected skin was 15% longer than those in normal skin; at Week 8, the mean length of lesional dendritic melanocytes became the same as those in normal skin. Additionally, the mean width of dendritic melanocytes decreased from being 4% wider to only 2% wider than those in normal skin. After 8 weeks of treatment, an improvement of MASI score was noted, mainly attributable to a reduction in lesional area. OCT showed no notable change regarding melanin, but a decrease in length and width of dendritic melanocytes was noted in the lesional skin of melasma patients.

SPRR1B+ keratinocytes prime oral mucosa for rapid wound healing via STAT3 activation

Oral mucosal wounds exhibit accelerated healing with reduced scarring compared to cutaneous wounds, representing an optimal wound healing paradigm. However, the specific cellular subtypes orchestrating the efficient healing of mucosal tissues remain elusive. Through a comprehensive analysis integrating bulk-mRNA and single-cell sequencing data during the wound healing process in oral mucosa and skin, we have delineated a distinct set of genes markedly upregulated during tissue repair. This collection of wound healing-associated genesets was highly enriched in a specific keratinocyte subpopulation identified as STAT3-activated SPRR1B+ keratinocytes. Notably, despite the inherent rapidity of oral mucosal healing, the induction of SPRR1B+ keratinocytes is evident in both skin and mucosal wound healing processes in murine model. Intriguingly, these wound healing-promoting SPRR1B+ keratinocytes, which are induced via STAT3 activation, inherently abundant in unwounded normal mucosa but absent in normal skin. SPRR1B knockdown significantly inhibits mucosal keratinocyte migration, a critical attribute for effective wound healing. In summary, through analysis of human oral and skin wound healing processes at single-cell resolution, coupled with validation in murine model, suggests STAT3-activated SPRR1B+ keratinocytes are associated with the rapid mucosal repair process. This discovery underscores the potential application of SPRR1B+ keratinocytes in the therapeutic management of chronic or non-healing wounds.

Intralesional immunotherapy of cutaneous warts using tuberculin purified protein derivative and vitamin D3 – A randomized comparative study

Objectives: Numerous studies have been conducted on the clinical efficacy of immunotherapeutic agents in the treatment of cutaneous warts showing variable results. The present study aimed to compare the clinical efficacy and safety of intralesional tuberculin purified protein derivative (PPD) and Vitamin D3 therapy in recurrent and recalcitrant extra-genital cutaneous warts. Material and Methods: This study was conducted as a prospective, randomized, comparative, and single-blind study. A total of 104 patients were randomly distributed into two treatment groups: Group A (Tuberculin PPD, n = 53) and Group B (Vitamin D3, n = 51). Each patient in Group A received an intralesional injection of 0.1 mL tuberculin PPD (5 Tuberculin Units), while each patient in Group B received an intralesional injection of 0.2 mL Vitamin D3 (Cholecalciferol containing 120,000 IU). The injections were given at the initial visit (week 0) and after every 2 weeks for a maximum of four sessions (weeks 2, 4, and 6). The largest wart was selected for intralesional therapy. The categorization of clinical response was done based on the percent reduction in the size of warts into complete (appearance of normal skin), marked (&gt;50% reduction), moderate (&lt;50% reduction), and inadequate (no change in warts) responses. Adverse effects (if any) were recorded during each patient visit. The final response was evaluated at 6 months follow-up from the last treatment session. Results: Regarding the response of patients to tuberculin PPD therapy, out of a total of 53 patients, 40 (75.5%) showed a complete response. Regarding the response of patients to Vitamin D3 therapy, out of a total of 51 patients, 36 (70.6%) showed a complete response. However, the difference in the response to the treatment between the two groups was statistically insignificant (P = 0.402). Conclusion: Both intralesional tuberculin PPD and Vitamin D3 are effective and safe in the treatment of all recurrent and recalcitrant extra-genital cutaneous warts.

In vivo Antifungal Efficacy and Safety of Natural Compounds for Topical Treatment of Cutaneous Candidiasis

In vivo toxicity and antifungal therapeutic evaluation of selected natural compounds for topical applications was analyzed using standard methods. The natural compounds, blue vitriol, brimstone, trona, alum, palm ash and black stone were hygienically selected and purchased at a local market in southeastern Nigeria. The test organisms were isolated from high vaginal swab specimens obtained from cases of cutaneous candidiasis. The isolates were identified based on their morphological, physiological and molecular characteristics. The toxicological screening of the test samples was done using Draize’ skin irritancy test, Murine local lymph node assay (LLNA) and necropsy. The in vivo evaluation of antifungal activity of the solutions was done using eight-week-old albino rats weighing 120g – 150g. The animals were infected with the Candida isolates percutaneously; and treated using various formulations of the natural compounds. The skin sections were carefully observed for histopathological changes, before and after treatment. The total yeast counts of the infected skin tissues were also determined. The isolates include Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Draize’ skin test and Murine local lymph node assay showed no observable skin irritancy reaction (P&gt;0.05). The normal skin architecture of the infected animals was restored after 5 days of treatment with the test samples; while the total yeast count decreased from 108 CFU/mL to 102 CFU/mL. The findings have revealed that natural compounds are effective as well as non-toxic topically, in treatment of cutaneous candidiasis.

Association of ABO and Rhesus blood groups with symptom emergence in scabies: a cross-sectional study.

Scabies is a contagious skin condition caused by the Sarcoptes scabiei mite. It can lead to various clinical reactions, ranging from no symptoms at all to noticeable skin lesions and severe itching within the same household. We aimed to investigate the potential role of blood groups in the emergence of disease symptoms by comparing the scabies patients with asymptomatic co-residents. This study comprised 102 patients infected with scabies from index cases and 111 asymptomatic co-residents. The index cases where symptoms first appeared were excluded. Among patients with scabies, 34 individuals (33.3%) had type A blood group, 12 (11.8%) had type B, 27 (26.5%) had type AB, and 29 (28.4%) had type O. Of these patients, 101 (99%) were Rh+, while 1 (1%) was Rh-. In asymptomatic contacts, 61 individuals (55%) had type A, 9 (8.1%) had type B, 1 (0.9%) had type AB, and 40 (36%) had type O blood group. Of these, 102 (91.9%) were Rh+, and 9 (8.1%) were Rh-. A significant difference was observed between the two groups concerning the frequency of ABO, Rh, and ABO*Rh blood groups (p < 0.05). The prevalence of B + and AB + blood groups was higher in scabies patients compared to asymptomatic contacts. The study results showed a significant association between the emergence of scabies symptoms with blood groups. Our results highlight the importance of more research into the roles of blood group antigens in normal skin epithelium and their involvement in the etiopathogenesis of scabies.

Semaglutide functional electrospinning nanofiber membrane rescues apoptosis and promotes diabetic wound healing

The healing of diabetic wounds is a difficult problem due to decreased proliferation, and migration of epidermal and endothelial cells. Here we reported semaglutide-loaded nanofiber membrane to promote diabetic wound healing through suppressing reactive oxygen species production and accelerating angiogenesis in a diabetic rat model. The fiber membrane was prepared by an electrostatic spinning technique. The fiber membrane consisted of thermalplastic polyurethane elastomer, polyvinyl butyral ester, zein and semaglutide (SMGT). The fiber membrane had a uniformly distributed diameter, suitable water vapor transmission rate, good water absorption and retention properties. In vivo data determined that the SMGT-loaded nanofiber membrane was able to promote normal skin pathological structure formation in regenerated tissue. In vitro experiments displayed that SMGT might facilitate HG-induced endothelial cell dysfunction by inhibiting ROS production. The present study provided a theoretical basis for the extensive application of SMGT in the treatment of diabetic ulcers and other wounds.

Novel Pannexin 1 isoform is increased in cancer.

Pannexin 1 (PANX1) is upregulated in many cancers, where its activity and signalling promote tumorigenic properties. Here, we report a novel ∼25 kDa isoform of human PANX1 (hPANX1-25K) which lacks the N-terminus and was detected in several human cancer cell lines including melanoma, osteosarcoma, breast cancer and glioblastoma multiforme. This isoform was increased upon hPANX1 CRISPR/Cas9 deletion targeting the first exon near M1, suggesting a potential alternative translation initiation (ATI) site. hPANX1-25K was confirmed to be a hPANX1 isoform via mass spectrometry, can be N-linked glycosylated at N254, and can interact with both β-catenin and full length hPANX1. A double deletion of hPANX1 and hPANX1-25K reduces cell growth and viability in cancer cells. hPANX1-25K is prevalent throughout melanoma progression, and its levels are increased in squamous cell carcinoma cells and patient-derived tumours, compared to keratinocytes and normal skin, indicating that it may be differentially regulated in normal and cancer cells.