Rapamycin blocks the IL-13-induced deficiency of Epidermal Barrier Related Proteins via upregulation of miR-143 in HaCaT Keratinocytes.

Interleukin (IL)-13 plays a key role in the pathogenesis of atopic dermatitis (AD). Our preliminary study demonstrated that forced expression of miR-143 could block IL-13-induced down-regulation of epidermal barrier related proteins in epidermal keratinocytes. As previous studies suggested that miR-143 expression was regulated by mammalian target of rapamycin (mTOR) signaling pathway, we investigated the mechanism of mTOR signaling pathway in the epidermal barrier dysfunction of AD. The HaCaT cells were stimulated by IL-13 and subsequently treated with rapamycin. The expression levels of miR-143, IL-13 receptor α1 (IL-13Rα1), p-mTOR, p-S6K1, p-Akt, and epidermal barrier related proteins were analyzed through RT-qPCR and/or western blotting. The current study showed that IL-13 increased the expression levels of p-mTOR, p-S6K1, and p-Akt, and that rapamycin blocked IL-13-induced down-regulation of miR-143, suppressed the IL-13Rα1 expression and up-regulated the expressions of filaggrin, loricrin, and involucrin in HaCaT cells. This study proposed that IL-13 could activate the mTOR signaling pathway, and confirmed the vital role of mTOR-miR-143 signaling axis in the pathogenesis of AD. It provided solid evidences regarding rapamycin as a potential effective therapeutic option in the management of AD.

DnaJA1/Hsp40 is co-opted by influenza A virus to enhance its viral RNA polymerase activity.

UNLABELLED: The RNA-dependent RNA polymerase (RdRp) of influenza A virus is a heterotrimeric complex composed of the PB1, PB2, and PA subunits. The interplay between host factors and the three subunits of the RdRp is critical to enable viral RNA synthesis to occur in the nuclei of infected cells. In this study, we newly identified host factor DnaJA1, a member of the type I DnaJ/Hsp40 family, acting as a positive regulator for influenza virus replication. We found that DnaJA1 associates with the bPB2 and PA subunits and enhances viral RNA synthesis both in vivo and in vitro. Moreover, DnaJA1 could be translocated from cytoplasm into the nucleus upon influenza virus infection. The translocation of DnaJA1 is specifically accompanied by PB1-PA nuclear import. Interestingly, we observed that the effect of DnaJA1 on viral RNA synthesis is mainly dependent on its C-terminal substrate-binding domain and not on its typical J domain, while the J domain normally mediates the Hsp70-DnaJ interaction required for regulating Hsp70 ATPase activity. Therefore, we propose that DnaJA1 is co-opted by the influenza A virus to enter the nucleus and to enhance its RNA polymerase activity in an Hsp70 cochaperone-independent manner. IMPORTANCE: The interplay between host factors and influenza virus RNA polymerase plays a critical role in determining virus pathogenicity and host adaptation. In this study, we newly identified a host protein, DnaJA1/Hsp40, that is co-opted by influenza A virus RNA polymerase to enhance its viral RNA synthesis in the nuclei of infected cells. We found that DnaJA1 associates with both PB2 and PA subunits and translocates into the nucleus along with the nuclear import of the PB1-PA dimer during influenza virus replication. Interestingly, the effect of DnaJA1 is mainly dependent on its C-terminal substrate-binding domain and not on its typical J domain, which is required for its Hsp70 cochaperone function. To our knowledge, this is the first report on a member of the Hsp40s that is specifically involved in regulating influenza virus RNA polymerase. Targeting the interactions between polymerase subunits and DnaJA1 may provide a novel strategy to develop antiviral drugs.

Naturally occurring PAE206K point mutation in 2009 H1N1 pandemic influenza viruses impairs viral replication at high temperatures.

The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century. In this study, we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients. Sequence comparison of the three main protein subunits (PB2, PB1, and PA) of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution (E206K) was responsible for the observed impaired replication phenotype. Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus's pathogenicity in vivo. Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1-PA complex to the nucleus at high temperature (39.5 â€‹°C). Hence, this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines.

Collagen/gelatin and polysaccharide complexes enhance gastric retention and mucoadhesive properties.

This article has focused on collagen-gelatin, the gelation process, as well as blend interaction between collagen/gelatin with various polysaccharides to boost mucoadhesion and gastric retention. The interaction between mucoadhesive materials and mucin layers is of significant interest in the development of drug delivery systems and biomedical applications for effective targeting and prolonged time in the gastrointestinal tract. This paper reviews the current advancement and mucoadhesive properties of collagen/gelatin and different polysaccharide complexes concerning the mucin layer and interactions are briefly highlighted. Collagen/gelatin and polysaccharide blends biocompatible and biodegradable, the complex biomolecules have shown encouraging mucoadhesive properties due to their cationic nature and ability to form hydrogen bonds with mucin glycoproteins. The mucoadhesion mechanism was attributed to the electrostatic interactions between the positively charged amino (NH2) groups of blend biopolymers and the negatively charged sialic acid residues present in mucin glycoprotein. At the end of this article, the encouraging prospect of collagen/polysaccharide complex and mucin glycoprotein is highlighted.

Treatment of non-tuberculosis mycobacteria skin infections.

Non-tuberculosis mycobacteria (NTM) skin infections have become increasingly prevalent in recent years, presenting a unique challenge in clinical management. This review explored the complexities of NTM infections localized to the superficial tissues and provided valuable insights into the optimal therapeutic strategies. The antibiotic selection should base on NTM species and their susceptibility profiles. It is recommended to adopt a comprehensive approach that considers the unique characteristics of superficial tissues to improve treatment effectiveness and reduce the incidence of adverse reactions, infection recurrence, and treatment failure. Infection control measures, patient education, and close monitoring should complement the treatment strategies to achieve favorable outcomes in managing NTM skin infections. Further efforts are warranted to elucidate factors and mechanisms contributing to treatment resistance and relapse. Future research should focus on exploring novel treatment options, innovative drug development/delivery platforms, and precise methodologies for determining therapeutic duration. Longitudinal studies are also needed to assess the long-term safety profiles of the integrated approaches.

Slow Mohs micrographic surgery for nail apparatus melanoma in situ.

BACKGROUND: Nail apparatus melanoma is a malignant tumor with a high incidence in Chinese melanoma patients. Slow Mohs micrographic surgery is an emerging technique for treating nail apparatus melanoma in situ (NAMIS). OBJECTIVE: This study evaluated the efficacy and safety of slow Mohs micrographic surgery for treating NAMIS. METHODS: Patients were enrolled in this retrospective study and treated in a single center from October 1, 2016, to June 30, 2022. Each patient underwent standard slow Mohs micrographic surgery, and follow-up was regularly conducted at clinics. RESULTS: Ten patients were enrolled in the study. Two patients underwent one Mohs stage, seven underwent two Mohs stages, and one underwent seven Mohs stages. The resection margin ranged from 5 to 25 mm. No severe complications were reported in the treatment, and recurrence of NAMIS was not observed during the follow-up period. CONCLUSION: Slow Mohs micrographic surgery is a valuable surgical method to treat NAMIS that preserves digit function and can be well tolerated by patients.

Skin diseases of the nipple and areola complex: A case series study from China.

Background: Skin diseases of the nipple and areola complex (NAC) are numerous and difficult to diagnose, which is a great challenge for clinicians. A better understanding of the clinical features of NAC skin diseases is of great value for the correct diagnosis. Methods: To investigate the clinical characteristics of skin diseases of the NAC, we retrospectively analyzed the demographic data, disease constitution, rash characteristics, inconsistency between the clinical and pathological diagnosis from 260 patients with NAC lesions that were confirmed by histopathology at Peking Union Medical College Hospital, China from 2012 to 2022. Results: The patients' average age was 43.6 (8 to 82) years, and the ratio of females to males was 13.4:1. Out of the 260 patients biopsied, the most common diseases were eczema, Paget's disease (PD), adenoma of the nipple (AN), seborrheic keratosis (SK), cutaneous metastasis of breast cancer, wart, soft fibroma, and hyperkeratosis of the nipple and areola. There were 77 (29.6%) patients with inconsistency between the clinical impressions and pathological diagnoses. AN was the most clinically misdiagnosed condition, most commonly presumed to be PD or eczema. Conclusion: Eczema and PD are the most common biopsied NAC skin diseases. Late onset, unilateral involvement, and predilection for the nipple are several characteristics of PD, which are different from eczema. NAC skin diseases are easily misdiagnosed clinically, especially AN.

A Bibliometric Analysis of Melanoma Treated with Vaccinations Research from 2013 to 2023: A Comprehensive Review of the Literature.

BACKGROUNDS: Melanoma is a malignant tumor that originates from melanocytes and is known for its aggressive behavior and high metastatic potential. In recent years, vaccine therapy has emerged as a promising approach for the treatment of melanoma, offering targeted and individualized immunotherapy options. In this study, we conducted a bibliometric analysis to assess the global research trends and impact of publications related to melanoma and vaccine therapy. METHODS: We retrieved relevant literature from the Web of Science database from the past decade (2013-2023) using keywords such as "melanoma", "vaccine therapy", and "cancer vaccines". We used bibliometric indicators including publication trends, citation analysis, co-authorship analysis, and journal analysis to evaluate the research landscape of this field. RESULTS: After screening, a total of 493 publications were included in the analysis. We found that melanoma and vaccine therapy have gained significant attention in the field of cancer immunotherapy, as evidenced by the numerous research output and increasing citation impact. The United States, China, and their organizations are the leading countries/institutes in terms of publication output, and collaborative research networks are prominent in this field. Clinical trials evaluating the safety and efficacy of vaccination treatment in melanoma patients are the focus of research. CONCLUSIONS: This study provide valuable insights into the novel research landscape of vaccine treatment of melanoma, which could inform future research directions and facilitate knowledge exchange among researchers in this field.

Ocular Adverse Effects in Atopic Dermatitis Patients Treated With Dupilumab: A Bibliometric Analysis.

Background: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin disorders. Dupilumab, the first targeted biological drug approved for the treatment of AD, has been widely used, along with increasing ocular adverse effects (AEs). Objective: To perform a bibliometric analysis of all the qualified literature involving ocular AEs during the treatment of AD with dupilumab. Methods: Relevant studies were extracted from the Web of Science database and screened by researchers. The bibliographic analysis was performed using the VOSviewer. Results: A total of 138 articles were enrolled in this study. The first study was published in 2016 by Oregon Health and Science University from the United States. The majority of publications were published in the past 3 years. British Journal of Dermatology published the highest number of articles. The United States was the country with the most publications. Sanofi (France) and Regeneron Pharmaceuticals (USA) were the leading organizations with the most contributions. Conjunctivitis was the most common ocular AE. The management of AD will continue to be the research hotspot and development trend in this area. The milestone research is the first article "Two Phase 3 Trials of Dupilumab vs. Placebo in Atopic Dermatitis" published in the New England Journal of Medicine. Most of the top 10 papers were mainly randomized, placebo-controlled phase 2 and phase 3 clinical trials and real-life large cohort studies. Conclusions: This study may help better understand ocular AEs in the dupilumab treatment of AD, and grasp the research trends and most influential topics in this field.

Structure of type II collagen from sturgeon cartilage and its effect on adjuvant-induced rheumatoid arthritis in rats.

The purpose of this paper was to extract and characterize type II collagen of sturgeon cartilage (SC-CII), and to explore the effects of taking SC-CII orally on rheumatoid arthritis (RA) in rats. SC-CII showed a triple-helix structure (RPN = 0.12), with d1 of 11.82 Å and d2 of 4.08 Å, which was analyzed by FT-IR, CD, XRD, and MS. It was constructed of the repeating tripeptide unit Gly-X-Y, where X and Y are generally Pro or Hyp, proved by amino acid composition and peptide mass fingerprinting. Furthermore, the effects of SC-CII on RA were evaluated. Ankle thickness was significantly decreased in SC-CII groups, with changes in lymphocyte proliferation also observed. Compared with the model control group, there was an evident decrease in TNF-α, IL-1ß, COX-2, MCP-1, and TLR-4 mRNA levels, but no remarkable differences in APF, MMP-3, and MyD88 mRNA levels in the SC-CII groups. In addition, TNF-α, IL-1ß, RF, Anti-CII Ab were significantly reduced in the SC-CII groups, proved by ELISA. Therefore, SC-CII showed alleviating effects on RA through the TLR4/MyD88-NFκB pathway.

Association between metabolic syndrome and psoriasis: a meta-analysis of observational studies with non-psoriasis control groups.

INTRODUCTION: Psoriasis is a highly prevalent condition that affects the quality of life of affected individuals. Several studies have indicated an association between psoriasis and metabolic syndrome (MS). However, the results were inconsistent. The objective of this study was to evaluate the relationship between psoriasis and MS. MATERIAL AND METHODS: Electronic databases (PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane) were searched systematically for published studies up to November 2, 2018. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between psoriasis and MS. The heterogeneity of the study was estimated with the I2 statistic and analyzed by meta-regression and subgroup analyses. RESULTS: Twenty-two studies with a total of 137,053 participants were included in this meta-analysis. Psoriasis was associated with MS and the combined OR (95% CI) was 2.02 (1.67-2.43). The results showed high heterogeneity (I 2 = 83.60%, p < 0.001) and no publication bias among the included studies (p = 0.119). The source of controls may have influenced the heterogeneity according to the meta-regression. There was no heterogeneity in studies with matched non-psoriasis control groups according to the subgroup analysis. CONCLUSIONS: Psoriasis was associated with MS. The source of the control group was an influencing factor on heterogeneity in this study. Treating for MS in patients with psoriasis might improve psoriasis and reduce the risk of cardiovascular disease.

Generalized multinucleate cell angiohistiocytoma with possible origin from fibroblasts: A clinicopathological study of 15 cases.

Multinucleate cell angiohistiocytoma (MCAH) is a vascular and fibrohistiocytic proliferation with unknown pathogenesis. Clinical lesions tend to be localized to an anatomical area. Exceptionally, the generalized variant is rare. This study reports three cases of generalized MCAH, and analyzes the clinicopathological features of 15 cases reviewed in the published work. Compared with the localized variant, generalized MCAH affected both sexes equally, had an earlier age of onset and a predilection for the trunk and extremities. Histopathologically, the most characteristic feature is the giant, bizarre multinucleate cells with angulated cytoplasm. Systemic diseases or abnormal immune conditions were revealed in six patients with generalized MCAH. For the first time, we found that the present cases showed increased elastic fibers in the affected areas, suggesting that the synthetic function of fibroblasts was active. This study suggested that MCAH originates from fibroblasts and is a distinct entity with potential correlation with abnormal immune states.

The efficacy and safety of DermalaxTM DEEP in the correction of moderate to severe nasolabial folds: a multicenter, randomized, double-blind clinical study.

BACKGROUND: To investigate the efficacy and safety of Dermalax in the correction of moderate to severe nasolabial folds (NLFs) compared to Restylane. METHODS: A total of 324 subjects with moderate to severe NLFs were enrolled in this multicenter, randomized, double-blind, active-controlled clinical study. Eligible subjects were randomly assigned to the test group received Dermalax injection (n = 162) or control group received Restylane injection (n = 162). Clinical efficacy and safety were assessed based on the Wrinkle Severity Rating Scale (WSRS) and the Global Esthetic Improvement Scale(GAIS) at weeks 2, 8, 16, 24, 36 and 48 weeks after injection. RESULTS: At week 24, similar improvements of effective rate were obtained on the Dermalax group (93.75%) and Restylane group (89.44%). Significances were found at 36 weeks and 48 weeks after injection, Dermalax seemed be better than Restylane in maintaining the effect in the later period. The improvement of mean WSRS score for test group was superior to that of control group with significance. GAIS scores rated at week 24 were 1.65 VS 1.94 (p < .001) and 2.10 VS 2.27 (p = .060), seperately. CONCLUSIONS: Dermalax was no inferior to or better than that of the control filler Restylane in correcting of moderate to severe NLFs in Chinese subjects.

Lack of association of the IL-1RN and IL-10 polymorphisms with risk of psoriasis: A meta-analysis.

BACKGROUND: The present study carried out a meta-analysis to investigate whether the interleukin-1 receptor antagonist (IL-1RN) VNTR polymorphism and three IL-10 single-nucleotide polymorphisms (SNPs) rs1800896, rs3021097, and rs1800872 are associated with psoriasis risk. METHODS: Wanfang, China National Knowledge Infrastructure, Medline, and PubMed databases were searched for potential studies published until 2 November 2017. Forest plots were generated. RESULTS: Thirteen case-control studies were included in the review. The results of meta-analyses revealed no association of the IL-1RN*2 allele with psoriasis in the overall populations (odds ratio [OR] = 1.16, 95% confidence intervals [CI]: 0.89-1.50, p = 0.279), Asians (OR = 1.27, 95% CI: 0.73-2.23, p = 0.403), and Caucasians (OR = 1.04, 95% CI: 0.88-1.23, p = 0.669). Under the allelic model, there was no statistically significant association of psoriasis with the IL-10 SNPs rs1800896 (G allele vs. A allele: OR = 1.03, 95% CI: 0.90-1.18, p = 0.639), rs3021097 (C allele vs. T allele: OR = 1.17, 95% CI: 0.88-1.56, p = 0.288), and rs1800872 (C allele vs. A allele: OR = 1.01, 95% CI: 0.81-1.25, p = 0.951). No publication bias was found by Egger's test and Begg's funnel plots. CONCLUSION: Current published studies fail to support an association of the IL-1RN VNTR polymorphism and IL-10 SNPs rs1800896, rs3021097, and rs1800872 with psoriasis risk.