Interplay between diabetes mellitus and atopic dermatitis.

Inflammatory dermatoses such as atopic dermatitis (AD) have long been linked to the pathogenesis of diabetes mellitus. Indeed, numerous studies show an increased risk of diabetes mellitus in individuals with AD although lower prevalence of diabetes mellitus is also observed in few studies. Though the underlying mechanisms accounting for the reciprocal influence between these two conditions are still unclear, the complex interplay between diabetes mellitus and AD is attributable, in part, to genetic and environmental factors, cytokines, epidermal dysfunction, as well as drugs used for the treatment of AD. Proper management of one condition can mitigate the other condition. In this review, we summarize the evidence of the interaction between diabetes mellitus and AD, and discuss the possible underlying mechanisms by which these two conditions influence each other.

Preventive and Therapeutic Benefits of Natural Ingredients in Photo-Induced Epidermal Dysfunction.

BACKGROUND: The skin, particularly the epidermis, is subjected to various external stresses, including ultraviolet (UV) irradiation. UV irradiation, mainly UVB at wavelength of 280-315 nm, can alter several epidermal functions, including cutaneous inflammation, epidermal hyperproliferation, DNA damage, disruption of epidermal permeability barrier and reduction in stratum corneum hydration levels. Because of the negative impacts of UVB irradiation on epidermal functions, great efforts have been made to develop regimens for the protection of alterations in epidermal function induced by UV irradiation. SUMMARY: While sunscreen can provide physical barrier to UV light, some natural ingredients can also effectively protect the skin from UVB irradiation-induced damages. Studies have demonstrated that either topical or oral administrations of some natural ingredients attenuate UVB irradiation-induced alterations in the epidermal function. The underlying mechanisms by which natural ingredients improve epidermal functions are attributable to antioxidation, stimulation of keratinocyte differentiation, increases in the content of epidermal natural moisturizers and inhibition of inflammation. KEY MESSAGE: Some natural ingredients exhibit protective and therapeutical benefits in photo-induced epidermal dysfunctions via divergent mechanisms.

Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES).

BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (P<0.05); variants in FOXL2 and MYH6 were found in patients with isolated, sporadic ASD (P<5×10^-4). CONCLUSIONS This was the first study that demonstrated variants in FOXL2 and HYDIN associated with sporadic ASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.

Efficacy and safety of brivudine for the treatment of herpes zoster: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine. METHODS: Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted. RESULTS: The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy (p = .0002) and incidence of postherpetic neuralgia (p = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups (p = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ (p > .05). CONCLUSIONS: Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.

Circ_0000006 and circ_0000160 regulate hsa-let-7e-5p/UBQLN4 axis in aortic dissection progression.

Aortic aneurysms (AA) and aorta dissection (AD) are life-threatening conditions with a rising incidence and high mortality rate. Recent research has linked non-coding RNAs to the regulation of AA and AD progression. In this study, we performed circRNA sequencing, microRNA (miRNA) sequencing, and messenger RNA (mRNA) sequencing on plasma samples from AA and AD patients to identify the key circRNA-miRNA-mRNA axis involved in the transition from AA to AD. Our results showed elevated levels of circ_0000006 and circ_0000160, along with decreased levels of hsa-let-7e-5p in AD samples compared to AA samples. Predictive analysis suggested that circ_0000006 and circ_0000160 potentially target hsa-let-7e-5p, which in turn may bind to the mRNA of Ubiquilin 4 (UBQLN4). In an AD cell model using vascular smooth muscle cells (VSMCs), silencing circ_0000006 and circ_0000160 attenuated the effects of platelet-derived growth factor (PDGF)-induced phenotypic changes, proliferation, and migration. This effect was partially reversed by inhibiting hsa-let-7e-5p. Furthermore, we found that overexpression of UBQLN4 counteracted the effects of hsa-let-7e-5p, suggesting UBQLN4 as a downstream mediator of hsa-let-7e-5p. In an animal model of AD, knockdown of circ_0000006 and circ_0000160 also showed protective effects against aortic septation. Overall, our findings indicate that the upregulation of circ_0000006 and circ_0000160 contributes to the progression from AA to AD by influencing abnormal phenotypic changes, migration, and proliferation of VSMCs. The Hsa-let-7e-5p/UBQLN4 axis may play a critical role in AD development. Targeting circ_0000006 and circ_0000160 could be a potential therapeutic strategy for preventing the progression of AD.

Benefits of topical natural ingredients in epidermal permeability barrier.

Because of the crucial role of epidermal permeability barrier in regulation of cutaneous and extracutaneous functions, great efforts have been made to identify and develop the regimens that can improve epidermal permeability barrier function. Studies have demonstrated that oral administration of natural ingredients can improve epidermal permeability barrier in various skin conditions, including inflammatory dermatoses and UV-irradiation. Moreover, topical applications of some natural ingredients can also accelerate the repair of epidermal permeability barrier after acute barrier disruption and lower transepidermal water loss in the intact skin. Natural ingredient-induced improvements in epidermal permeability barrier function can be attributable to upregulation of keratinocyte differentiation, lipid production, antioxidant, hyaluronic acid production, expression of aquaporin 3 and sodium-hydrogen exchanger 1. In this review, we summarize the benefits of topical natural ingredients in epidermal permeability barrier in normal skin with or without acute barrier disruption and the underlying mechanisms.

A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE.

Methylation variabilities of inflammatory cytokines play important roles in the development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS). With heightened focus on personalized and precise medicine, it is necessary to compare and contrast the difference and similarity of cytokine methylation status between the 3 most classic autoimmune diseases (AIDs). In this study, we integrated 5 Cytokine-Chips from genome-wide DNA methylation datasets of the 3 kind of AIDs, delta-beta value was calculated for intergroup difference, and comprehensive bioinformatics analyses of cytokine genes with aberrant methylations were performed. 125 shared differential methylation variabilities (DMVs) were identified. There were 102 shared DMVs with similar methylation status; 3 hypomethylated differential methylation regions (DMRs) across the AIDs were found, and all 3 DMRs were hypomethylated. DMRs (AZU1, LTBR, and RTEL1) were likely to serve as activator in the inflammatory process. Particularly, AZU1 and LTBR with hypomethylated TSS and first exon located in the promoter regions were able to trigger inflammation signaling cascades and play critical roles in autoimmune tautology. Moreover, functional epigenetic module (FEM) algorithm showed that different inflammatory networks are involved in different AIDs; 5 hotspots were identified as biologically plausible pathways in inducing or perpetuating of inflammation which are epigenetically deregulated in AIDs. We concluded methylation variabilities among the same cytokines can greatly impact the perpetuation of inflammatory process or signal pathway of AIDs. Differentiating the cytokine methylation status will serve as valuable resource for researchers alike to gain better understanding of the epigenetic mechanisms of the three AIDs. Even more importantly, better understanding of cytokine methylation variability existing between the three classic AIDs will aid in identification of potential epigenetic biomarkers and therapeutic targets. This trial is registered with ChiCTR-INR-16010290, a clinical trial for the treatment of rheumatoid arthritis with Warming yang and Smoothening Meridians.

Genome-wide identification of long non-coding RNA and mRNA profiling using RNA sequencing in subjects with sensitive skin.

Sensitive skin (SS) is a condition of subjective cutaneous hyper-reactivity. The role of long non-coding RNAs (lncRNAs) in subjects with SS is unclear. Therefore, the aim of the present study was to provide a comprehensive profile of the mRNAs and lncRNAs in subjects with SS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis presented the characteristics of associated protein-coding genes. In addition, a co-expression network of lncRNA and mRNA was constructed to identify potential underlying regulation targets; the results were verified by quantitative real-time PCR (qRT-PCR) and RNA-seq analyses in patients with SS and normal samples. Compared with the normal skin group, 266 novel lncRNAs and 6750 annotated lncRNAs were identified in the SS group. A total of 71 lncRNA transcripts and 2615 mRNA transcripts were differentially expressed (P < 0.05). The heat signature of the SS samples could be distinguished from the normal skin samples, whereas the majority of the genes that were present in enriched pathways were those that participated in focal adhesion, PI3K-Akt signaling, and cancer-related pathways. Five transcripts were selected for qRT-PCR analysis and the results were consistent with RNA-seq. The results suggested that LNC_000265 may play a role in the epidermal barrier structure of patient with SS. The data suggest novel genes and pathways that may be involved in the pathogenesis of SS and highlight potential targets that could be used for individualized treatment applications.

Insight into immunocytes infiltrations in polymorphous light eruption.

Polymorphous light eruption (PLE) which is one of the most common photodermatoses has been demonstrated to be immune-mediated disorder. Resistance to UV-induced immunosuppression resulting from differential immune cells infiltration and cytokines secretion has been highlighted in the pathogenesis of PLE. In this study, we reviewed differential patterns of immune cells infiltrations and cytokines secretion that may contribute to PLE occurrence and development.

Genome-Wide Analysis of mRNA and Long Noncoding RNA Profiles in Chronic Actinic Dermatitis.

Chronic actinic dermatitis (CAD), a photosensitive dermatosis, is characterized by inflammatory lesions, especially on sun-exposed skin. However, its pathogenesis remains unclear. In this study, second-generation RNA sequencing and comprehensive bioinformatics analyses of mRNAs and long noncoding RNAs (lncRNAs) were performed to determine the transcriptome profiles of patients with CAD. A total 6889 annotated lncRNAs, 341 novel lncRNAs, and 65091 mRNAs were identified. Interestingly, patients with CAD and healthy controls showed distinct transcriptome profiles. Indeed, 198 annotated (81.48%) and 45 novel (18.52%) lncRNAs were differentially expressed between the two groups. GO, KEGG, and RGSEA analyses of lncRNAs showed that inflammatory and immune response related pathways played crucial roles in the pathogenetic mechanism of CAD. In addition, we unveiled key differentially expressed lncRNAs, including lncRNA RP11-356I2.4 which plays a role probably by regulating TNFAIP3 and inflammation. qRT-PCR data validated the differentially expressed genes. The newly identified lncRNAs may have potential roles in the development of CAD; these findings lay a solid foundation for subsequent functional exploration of lncRNAs and mRNAs as therapeutic targets for CAD.

Pivotal MicroRNAs in Melanoma: A Mini-Review.

Melanoma is a common skin cancer associated with ultraviolet light exposure and genetic variance. However, the etiology and molecular mechanisms of melanoma remain unknown. Recent studies have shown that microRNAs (miRNAs) can play key roles in the development and prognosis of this disease. In this study, we reviewed several pivotal miRNAs that may contribute to melanoma by involvement in the processes of invasion, migration, and metastasis of melanoma cells.

The null polymorphism of the GSTM1/T1 gene is not associated with susceptibility to systemic lupus erythematosus: a meta-analysis.

Previous studies have suggested that the null polymorphism of the glutathione S-transferases M1/T1 (GSTM1/T1) gene may be associated with the risk of developing systemic lupus erythematosus (SLE). We further explored this potential association using a meta-analysis. A systematic literature search was carried out in the scientific literature databases and we used odds ratios (OR) and 95 % confidence intervals (CIs) to evaluate the strength of this association. All statistical analyses were calculated using Stata software 11.0, and Bonferroni correction was used to adjust the p values. Nine eligible articles with 1,850 patients and 2,826 controls were identified. Our results showed the null polymorphism of the GSTM1 gene was associated with SLE in East Asians (OR 1.32, 95 % CI 1.04-1.69, p = 0.024), but not in Europeans and Africans. However, when Bonferroni corrections were applied (p = 0.05/2 = 0.025), we could not be sure of this association. We further analysed the associations between the GSTT1 gene null polymorphism and the risk of SLE. The results of this investigation showed that this null polymorphism was not associated with susceptibility to SLE in all included populations. In conclusion, the null polymorphism of GSTM1/T1 gene may not be associated with the risk of SLE. More studies are needed to confirm this lack of association between key oxidative defense genes and susceptibility to SLE in the future.