Association between TH2 Cytokine Gene Polymorphisms and Risk of Bullous Pemphigoid.

BACKGROUND: T-helper 2 (Th2)-associated cytokines are involved in the pathogenesis of bullous pemphigoid (BP), an autoimmune skin disease. Increased expression of Th2 cytokines such as interleukin-4 (IL-4), IL-5, IL-6, IL-10, and IL-13 have been observed in serum, skin biopsies and/or blister fluid. This study aimed to uncover a possible association between Th2 cytokine genetic variations and susceptibility to BP. METHODS: In a cohort study, blood samples of BP patients and controls were obtained and variations in IL-4 (rs2243250 and rs2070874), IL-4R (rs1805010), IL-5 (rs2069812), IL-6 (rs1800795), IL-10 (rs1800896, rs1800871, and rs1800872), and IL-13 (rs1800925 and rs20541) were genotyped by PCR-RFLP assays. Furthermore, quantitative expression levels of IL-13 gene were evaluated by real-time RT-PCR analysis. RESULTS: Among the studied variations, a significantly higher frequency of the C-allele was observed in IL-13 gene variation (rs1800925) in the healthy individuals than BP patients. This may indicate a protective effect of C-allele on predisposition to BP. Considering individuals carrying polymorphic genotypes compared to wild genotype, the minor G-allele of IL-4R rs1805010 and A-allele of IL-13 rs20541 had a promotive and protective effect, respectively, on predisposing to the development of BP. No significant difference in IL-13 mRNA expression was detected between BP patients and healthy individuals. CONCLUSIONS: Our results indicate that IL-13 rs1800925 variation may be a protective genetic marker for the development of BP. Given this preventive effect against BP, therapeutic strategies could potentially be developed interfering with the functions of IL-13 cytokine, which seems to be integral in the pathogenesis of eosinophilic inflammatory disorders, such as BP.

Lichen planus and lichen planopilaris flare after COVID-19 vaccination.

We report two cases of lichen planus following COVID-19 vaccination in two middle-aged women, where the first patient presented with lichenplanopilaris (LPP) relapse and development of lichen planus 14 days after the second dose of AstraZeneca vaccine, and the other patient who had a previous scattered lesion of LP which extended and increased in severity after the first and second dose of Sinopharm. The suggested cause could be due to immune dysregulation and up regulation of T cell lymphocytes which was triggered after COVID-19 vaccination. What supports our hypothesis that LP had occurred due to COVID-19 vaccination, is that one of the patients responded successfully to Metronidazole. This means that the infection process after vaccination could be the cause in aggravating LP. To add, one of the suggested mechanisms for the appearance of LP or reactivation of a dormant LPP can be cytotoxic CD8 T-lymphocytes which increase the secretion of IFN-γ and IL-5 cytokines and may also result in basal keratinocytes' apoptosis leading to cutaneous manifestations. This was supported by the efficacy of Tofacitinib that was used in the other patient who presented with reactivation of LPP in addition to LP. Tofacitinib decrease the number of T cell infiltration and adjust IFN expression.

Efficacy and safety of chitosan-based bio-compatible dressing versus nanosilver (ActicoatTM ) dressing in treatment of recalcitrant diabetic wounds: A randomized clinical trial.

Chitosan has a biocompatible, biodegradable, and nontoxic nature. The effectiveness of Nano-chitosan films in the field of wound healing has been confirmed previously. The aim of this study was to compare the clinical efficacy and safety of two dressings (chitosan and nanosilver dressings) in the treatment of refractory diabetic wounds. A total of 25 eligible patients with chronic diabetic wound were included and randomly assigned to receive chitosan (13 patients) or nanosilver (12 cases) dressing. The dressings were applied on the wounds based on their protocols and patients were visited and examined by an experienced dermatologist every week. The clinical assessments and healing rates were recorded using diabetic-foot-infection (DFI) score at the 2nd, 4th, and 6th weeks during treatment. The study endpoint, safety and tolerability profile were also documented. The patterns of change in total 10-item-DFI wound scores did not differ significantly over time between the two groups. In both groups, the total 10-item-DFI wound score reduced continuously through the course of study. The mean percentage reduction of this score from baseline was 78.1% and 74.1% in the chitosan and nanosilver dressing groups, respectively. Both dressings were well tolerated and there were no adverse events. The relatively small sample size in both groups was the main limitation of the study. Our findings confirmed that chitosan may be safely and effectively used for the treatment of diabetic wounds just like the nanosilver (ActicoatTM ) dressing. Further studies are recommended with more volunteers and a longer follow-up period.

Laser treatment of benign melanocytic lesion: a review.

Treatment of pigmented lesions is one of the major challenges of laser and cosmetic practitioners. The most common pigmented lesions that are treated by lasers are melanocytic nevi, ephelides, solar lentigines, and café au lait macules. Melanin absorbs different wavelengths (500-1100 nm); thereby, treatment of various pigmented lesions requires the application of lasers with different wavelengths. Choosing the most appropriate type of laser depends on various factors such as the chromophore and the location of a specific lesion in the skin. In this paper, we aim to review the most efficient laser treatment protocols for each pigmented skin lesion and compare their efficacy in each part based on the previous studies.

Androgenetic alopecia and COVID-19: A review of the hypothetical role of androgens.

The coronavirus disease 2019 (COVID-19) has become the most emerging health issue globally. A prompt investigation regarding disease management and treatment is crucial for decreasing the burden of the disease. Many explorations and hypotheses have been posed, but the definite treatment has not been determined for COVID-19. Recent studies described a substantial prevalence of COVID-19 and also a higher rate of morbidity and mortality in men afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The gender-related discordance in COVID-19 infection may be due to hormonal differences, socioeconomic factors, genetic susceptibility, gender-related comorbidities, and habits like alcohol consumption. On the other hand, several studies proposed that androgens could improve the immune system and have a protective role in COVID-19, and decreased levels of androgens might be associated with unsatisfactory outcomes. In the field of dermatology, androgenetic alopecia (AGA) is correlated with a hyperandrogenic state and may be related to COVID-19 severity. Furthermore, recent research has assessed the plausible association of AGA and COVID-19. In this review, we investigate all evidence on AGA and its relationship with COVID-19, including the possible role of androgens in COVID-19 severity and outcomes as well as candidate androgen-related drugs for the treatment of COVID-19.

The utility of dermal fibroblasts in treatment of skin disorders: A paradigm of recessive dystrophic epidermolysis bullosa.

Dermal fibroblasts are the most accessible cells in the skin that have gained significant attention in cell therapy. Applying dermal fibroblasts' regenerative capacity can introduce new patterns to develop cell-based therapies to treat skin disorders. Dermal fibroblasts originate from mesenchymal cells and are located within the dermis. These cells are mainly responsible for synthesizing glycosaminoglycans, collagens, and components of extracellular matrix supporting skin's structural integrity. Preclinical studies suggested that allogeneic and autologous dermal fibroblasts provide widespread and beneficial applications for wound healing, burn ulcers, and inherited skin disorders. In this regard, generating induced pluripotent stem cells (iPSCs) from fibroblasts and gene-edited fibroblasts are promising approaches for treating skin disorders. Here, we aimed to review literature about ongoing and completed clinical trials that applied fibroblasts and bioengineered fibroblasts as therapeutic agents for various skin disorders. This review explores cell therapy protocols from the earliest phase of allogeneic and autologous fibroblasts development in different benches to translating them into bedside-level treatment for skin disorders, particularly recessive dystrophic epidermolysis bullosa.

IL12B and IL23R polymorphisms are associated with alopecia areata.

Alopecia areata is an autoimmune disease in which activation of autoreactive T cells and inflammatory immune signals target the hair follicles autoantigens. Although cytokines are involved in regulating autoimmune inflammation, the specific involvement of these molecules in the pathogenesis of alopecia areata has been remained unsettled. Here, a possible influence of IL12B, IL17A, and IL23R variations on susceptibility to alopecia areata in Iranian patients was investigated. Genotyping of IL12B (rs3212227), IL17A (rs2275913), and IL23R (rs10889677) variants were performed by extracting genomic DNA from patients and controls. Gene expression was analyzed by real-time RT-PCR. The frequency of IL12B and IL23R gene polymorphisms is significantly higher in the patients than controls, while no significant difference was found for IL17A. Stratification of the patients with respect to age at disease onset indicated that CC genotype of IL12B (rs3212227) and AA genotype of IL23R (rs10889677) gene polymorphisms are significantly associated with late-onset alopecia areata disease. In contrast to IL17A and IL23R, IL12B gene expression levels elevated in patients to that of controls, but genotypes had no effect on levels of gene expression. Overall, our data confirmed that the IL12B and IL23R polymorphisms are associated with the risk to develop alopecia areata in our population.

Melittin: a venom-derived peptide with promising anti-viral properties.

Despite tremendous advances in the development of anti-viral therapeutics, viral infections remain a chief culprit accounting for ongoing morbidity and mortality worldwide. Natural products, in particular animal venoms, embody a veritable cornucopia of exotic constituents, suggesting an immensurable source of anti-infective drugs. In this context, melittin, the principal constituent in the venom of the European honeybee Apis mellifera, has been demonstrated to exert anti-cancer, anti-inflammatory, anti-diabetic, anti-infective, and adjuvant properties. To our knowledge, there is no review appertaining to effects of melittin against viruses, prompting us to synopsize experimental investigations on its anti-viral activity throughout the past decades. Accumulating evidence indicates that melittin curbs infectivity of a diverse array of viruses including coxsackievirus, enterovirus, influenza A viruses, human immunodeficiency virus (HIV), herpes simplex virus (HSV), Junín virus (JV), respiratory syncytial virus (RSV), vesicular stomatitis virus (VSV), and tobacco mosaic virus (TMV). However, medication safety, different routes of administrations, and molecular mechanisms behind the anti-viral activity of melittin should be scrutinized in future studies.

Overlapping and Distinct FAS/FASLG Gene Polymorphisms in Alopecia Areata in an Iranian Population.

Alopecia areata (AA) is considered to have a multifactorial etiology and polymorphisms in certain genes have been shown to be associated with AA. Although several reports have investigated the effect of FAS/FAS ligand (FASLG) gene variations with predisposing to AA, genetic association of disease, however, varies among different ethnicities and no data have so far been reported in Iranian population. The present study aimed to uncover a possible association between variations in FAS/FASLG genes and AA. Genomic DNA was extracted from all samples and the SNPs of FAS (rs1800682) and FASLG (rs5030772) genes were genotyped in AA patients and controls. In addition, gene expression of FAS/FASLG was assessed by RT-PCR. Regarding FASLG, the frequency of the G-allele was significantly higher in the patients compared to the controls, indicating that the G-allele at this locus could be a risk for developing AA. In contrast, no association was found for rs1800682 (FAS) with AA. Similarly, compared to controls, FASLG gene expression was upregulated. While no association between clinical-demographic characteristics of the AA patients and their genotypes in FAS/FASL variations was observed, multivariate regression analysis indicated a correlation between the incidence of AA disease and its familial history as well as AG/GG genotypes of FASLG (rs5030772). In conclusion, our data indicate an association between FASLG rs5030772 variation and AA. However, previously reported the association of FAS rs1800682 polymorphism with AA was not observed here. These findings highlight overlapping and distinct genetic polymorphisms in an Iranian cohort which might influence the susceptibility to AA.

Anti-Staphylococcal and cytotoxic activities of the short anti-microbial peptide PVP.

Over the past years, short anti-microbial peptides have drawn growing attention in the research and trade literature because they are usually capable of killing a broad spectrum of pathogens by employing unique mechanisms of action. This study aimed to evaluate the anti-bacterial effects of a previously designed peptide named PVP towards the clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) in vitro. Secondary structure, cytotoxicity, and membrane-permeabilizing effects of the peptide were also assessed. PVP had a tendency to adopt alpha-helical conformation based upon structural predictions and circular dichroism spectroscopy (in 50% trifluoroethanol). The peptide showed MIC values ranging from 1 to 16 µg/mL against 10 strains of MRSA. In contrast to ciprofloxacin and gentamicin, PVP at sub-lethal concentration (1 µg/mL) did not provoke the development of peptide resistance after 14 serial passages. Remarkably, 1 h of exposure to 4 × MBC of PVP (8 µg/mL) was sufficient for total bacterial clearance, whereas 4 × MBC of vancomycin (8 µg/mL) failed to totally eradicate bacterial cells, even after 8 h. PVP showed negligible cytotoxicity against human dermal fibroblasts at concentrations required to kill the MRSA strains. The results of flow cytometric analysis and fluorescence microscopy revealed that PVP caused bacterial membrane permeabilization, eventually culminating in cell death. Owing to the potent anti-bacterial activity, fast bactericidal kinetics, and negligible cytotoxicity, PVP has the potential to be used as a candidate antibiotic for the topical treatment of MRSA infections.

The Association between Genetic Variation in Wnt Transcription Factor TCF7L2 (TCF4) and Alopecia Areata.

Background: Alopecia areata (AA) is a non-scarring hair loss with a polymorphous presentation ranging from patchy lesions to involvement of the entire scalp. The disease is the consequence of an autoimmune attack on hair bulbs that results in a premature transition of hair follicles to catagen and telogen. Thus the Wnt/ß-catenin signaling pathway that regulates the hair cycling might be involved in the pathogenesis of AA. Genetic variations in the components of Wnt/ß-catenin could greatly alter their adaptive mechanisms against an immunologic attack. Objectives: Our aim was to investigate the association between AA and genetic polymorphisms in the TCF7L2 gene, one of the most important components of the Wnt/ß-catenin pathway. Methods: This is a case-control study of 145 patients with AA and 152 healthy controls. Genotyping of the TCF7L2 gene (rs7903146) was performed via the ARMS-PCR method (amplification refractory mutation system- polymerase chain reaction). The allele and genotype distribution was compared between the two groups. Results: The frequency of the T allele (0.38 vs. 0.28, odds ratio = 1.56, 95% CI = 1.09-2.17, p = 0.013) and TT + CT genotypes (0.68 vs. 0.53, odds ratio = 1.88, 95% CI = 1.17-3.02, p = 0.008) were significantly higher in AA patients. Conclusions: This study indicates that the TCF7L2 gene variant is associated with AA. Its contribution to disease pathogenesis could either be through a hair cycling defect or dendritic cell dysregulation.

Methylprednisolone pulse therapy plus adjuvant therapy for pemphigus vulgaris: an analysis of 10 years' experience on 312 patients.

Steroid pulse therapy has shown satisfactory efficacy and safety in treating pemphigus vulgaris (PV). However, there is a paucity of data about the efficacy and safety of methylprednisolone, despite its frequent administration. The aim of this study is to evaluate the efficacy and safety of steroid pulse therapy in treating PV. In this 10-year retrospective cohort study, 312 patients with PV, who had received methylprednisolone pulse therapy, were included. Data of pulse therapy sessions, adjuvant medications, dosages, remission rates, complications, and mortalities were collected from all patients. A total of 276 patients out of 312 underwent the final follow-up at least 6 months after the last session of pulse therapy. Complete remission off therapy was achieved in 83 patients (30%), and 152 patients (55%) had complete remission on therapy. About 29 (10.5%) patients had lesions of pemphigus at the time of the study follow-up, and 26.8% of remained patients were on the minimal therapy. Methylprednisolone pulse therapy could be considered as an option for proper control of PV in severe cases. It might lead to shorter periods of hospitalization and reduce the need to take long-term high-dose oral steroid therapy.

Melittin: from honeybees to superbugs.

The emergence of antibiotic-resistant bacteria, dubbed superbugs, together with relative stagnation in developing efficient antibiotics has led to enormous health and economic problems, necessitating the need for discovering and developing novel antimicrobial agents. In this respect, animal venoms represent a rich repertoire of pharmacologically active components. As a major component in the venom of European honeybee Apis mellifera, melittin has a great potential in medical applications. In this mini-review, we summarize a multitude of studies on anti-bacterial effects of melittin against planktonic and biofilm-embedded bacteria. Several investigations regarding synergistic effects between melittin and antibiotics were also described. On the whole, the properties of melittin can open up new horizons in a range of biomedical areas, from agriculture to veterinary and clinical microbiology.

Losartan ointment relieves hypertrophic scars and keloid: A pilot study.

Keloid and hypertrophic scars are two types of fibrosis caused by extracellular matrix overexpression, and angiotensin II via AT1 receptor is known to play a key role in stimulation of fibrosis. A pilot placebo controlled single blind study was carried out on patients with hypertrophic scars and keloids. A total of 37 adult volunteers were randomly assigned into losartan 5% or placebo treatment groups. The treatment was performed twice a day for three months and a 6-month follow-up. The treatment was evaluated using Vancouver scar scale method. Totally, 30 participants were analyzed (Losartan ointment n = 20; placebo ointment n = 10; seven placebo volunteers left the study because they thought the treatment was not effective for them). In the losartan group, VSS scores dropped significantly (p < 0.01) both in keloid and hypertrophic scar patients. Vascularity and pliability were significantly reduced by losartan treatment (p < 0.05). It can be concluded that losartan potassium ointment (5%) can alleviate the keloid and hypertrophic scar.

Genetic variant association of PTPN22, CTLA4, IL2RA, as well as HLA frequencies in susceptibility to alopecia areata.

Alopecia areata (AA) is characterized by a genetically complex inheritance. HLA frequencies, as well as the single nucleotide polymorphism (SNP) in PTPN22, CTLA4, and IL2RA genes, have been described to be associated with AA susceptibility. So far, no independent replication of these studies has been reported, and no data exist on a possible association between AA disease and these SNPs or influence of HLA frequencies in Iranian population. A possible association between HLA-DRB1*11 alleles as well as a single variation in PTPN22, CTLA4, and IL2RA genes and patchy AA disease have been investigated in a cohort from Iran. Patient and control subjects were genotyped for PTPN22 (rs2476601), CTLA4 (rs3087243), and IL2RA (rs3118470) variations as well as HLA frequencies. Gene expression levels were analyzed by real-time RT-PCR. In contrast to PTPN22 and CTLA4 gene polymorphisms, a significant association was found between IL2RA SNP and susceptibility to AA in Iranian cohort. While gene expression levels of IL2RA and PTPN22 were higher in the patients than that of controls, CTLA4 expression levels found significantly lower in the patients. Despite a significant association between AA and HLA-DRB1*11 frequencies, the presence of DRB1*11 is not associated with PTPN22, CTLA4, or IL2RA gene SNPs. Although the minor allele in IL2RA SNP can be a significant determinant of AA disease development in Iranian population, reported an association between the PTPN22 and CTLA4 variations was not confirmed by our study. Furthermore, these genetic risk factors might act independently from HLA alleles.

The effect of cryopreservation on anti-cancer activity of human amniotic membrane.

Human amniotic membrane (AM) is an appropriate candidate for treatment of cancer due to special properties, such as inhibition of angiogenesis and secretion of pro-apoptotic factors. This research was designed to evaluate the impact of cryopreservation on cancer cell death induction and anti-angiogenic properties of the AM. Cancer cells were treated with fresh and cryopreserved amniotic condition medium during 24 h and cancer cell viability was determined by MTT assay. To evaluate angiogenesis, the rat aorta ring assay was performed for both fresh and cryopreserved AM within 7 days. In addition, four anti-angiogenic factors Tissue Inhibitor of Matrix Metalloproteinase-1 and 2 (TIMP-1 and TIMP-2), Thrombospondin, and Endostatin were measured by ELISA assay before and after cryopreservation. The results showed that the viability of cultured cancer cells dose-dependently decreased after treatment with condition medium of fresh and cryopreserved tissue and no significant difference was observed between the fresh and cryopreserved AM. The results revealed that the amniotic epithelial stem cells inhibit the penetration of fibroblast-like cells and angiogenesis. Moreover, the penetration of fibroblast-like cells in both epithelial and mesenchymal sides of fresh and cryopreserved AM was observed after removing of epithelial cells. The cryopreservation procedure significantly decreased anti-angiogenic factors TIMP-1, TIMP-2, Thrombospondin, and Endostatin which shows that angio-modulatory property is not fully dependent on proteomic and metabolomic profiles of the AM. These promising results demonstrate that cancer cell death induction and anti-angiogenic properties of the AM were maintained within cryopreservation; a procedure which can circumvent limitations of the fresh AM.

Antimicrobial Wound Dressing Containing Silver Sulfadiazine With High Biocompatibility: In Vitro Study.

Many patients all over the world suffer from acute wounds caused by traumas or burns. In most crucial cases, skin regeneration cannot be promoted spontaneously, and skin grafts are applied as the main treatment. However, this therapy has some drawbacks which motivate researchers to develop wound dressings. In this study, electrospun mats consisting of polycaprolactone (PCL) and polyvinyl alcohol (PVA) incorporated with silver sulfadiazine (SSD) are proposed to be used as antimicrobial wound dressings with the capability of cell seeding. Various amounts of SSD were loaded into PVA nanofibers, and the effects of SSD particles on the morphological characteristics of nanofibers, mechanical behaviors, and physical properties of the mats were studied for the first time. The cellular viability, antimicrobial properties of the scaffolds, and release behavior of silver were also examined. Finally, the best concentration of SSD was determined based on the quality of nanofibers, antibacterial features, and the ability of cellular attachment and proliferation. Fibronectin was also coated to enhance the biocompatibility of the selective scaffold. It was shown that the mats have appropriate mechanical properties with good handling ability in wet environment and also have a hydrophilic surface to adhere to the wound bed. Results indicate that SSD particles increase the fiber diameter and hydrophilic properties, while they weaken the mechanical characteristics of the mats. Furthermore, 5 wt% SSD/PVA was determined as the best concentration of SSD as it results in a desirable fiber quality for the mats with enough antimicrobial properties and acceptable cell proliferation on the surface. Coating fibronectin was also introduced as an effective method to increase the biocompatibility of the scaffolds incorporated with SSD particles.