Background: Cervical cancer (CC) is a common gynecological malignancy worldwide. Some patients perform serious resistance after chemotherapy, and long-stranded non-coding RNA MEG3 is reported to be involved in the regulation of chemoresistance in many solid tumors. However, its involvement in cervical adenocarcinoma has not been reported. Methods: Hela cell lines, cisplatin-resistant cell lines (Hela-CR) and nude mice were used in this study. After MEG3 was overexpressed or knocked down in cells by the lentivirus vector, cell growth was detected by the CCK-8 assay, and cell migration was evaluated using Transwell assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of MEG3, miR-21 and PTEN mRNA. Apoptosis was detected by flow cytometry. The targeting relationship between mRNAs was predicted and verified using dual-luciferase reporter gene experiments. Western blot was executed to examine Bax, cleaved-caspase 3, Bcl-2, PTEN and GAPDH expression. Cells were injected into the mice to form xenograft tumors to compare tumorigenesis capacity. Results: We demonstrated that MEG3 was down-regulated in cervical cancer by analyzing the TCGA database. Moreover, knockdown of MEG3 promoted CC cell proliferation, migration and inhibited the apoptosis. These changes of CC cells were more pronounced under cisplatin treatment. Further studies showed that the MEG3/miR-21/PTEN axis affected cisplatin sensitivity in cervical cancer cells, and these results of recue assay were used to confirm this conclusion. Conclusions: MEG3 performing as ceRNA promotes cisplatin sensitivity in CC cells through the miR-21/PTEN axis.

Objective. Apoptotic events mediated by mitochondrial injury play an important role on the onset of Pemphigus vulgaris (PV). The thioredoxin‐2 (Trx2)/apoptosis signal‐regulating kinase 1 (ASK1) signaling pathway is considered a key cascade involved on the regulation of mitochondrial injury. Hence, we have investigated the regulatory mechanism of the Trx2/ASK1 signaling in PV‐induced mitochondrial injury. Methods. Serum and tissue samples were collected from clinical PV patients to detect the oxidative stress factors, cell apoptosis, and expression of members from Trx2/ASK1 signaling. HaCaT cells were cultured with the serum of PV patients and transfected with Trx2 overexpression or silencing vector. Changes in the levels of reactive oxygen species (ROS), mitochondrial membrane potential (△ψm), and apoptosis were further evaluated. A PV mouse model was established and administered with Trx2‐overexpressing plasmid. The effect of ectopic Trx2 expression towards acantholysis in PV mice was observed. Results. A series of cellular and molecular effects, including (i) increased levels of oxidative stress products, (ii) destruction of epithelial cells in the skin tissues, (iii) induction of apoptosis in keratinocytes, (iv) reduction of Trx2 protein levels, and (v) enhanced phosphorylation of ASK1, were detected in PV patients. In vitro experiments confirmed that Trx2 can inhibit ASK1 phosphorylation, alleviate ROS release, decrease △ψm, and lower the apoptotic rate. Injection of Trx2‐overexpressing vectors in vivo could also relieve acantholysis and blister formation in PV mice. Conclusion. The Trx2/ASK1 signaling pathway regulates the incidence of PV mediated by mitochondrial injury.

Background: Chronic inflammation has been shown to promote cancer progression. Rosacea is indeed a long‐term inflammatory skin condition and had been reported to link with increased risk for several types of malignancies, but evidence for causality is lacking. Objectives: To systematically estimate the causal relationship between rosacea and several types of cancer, including cutaneous malignant melanoma (CMM), cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), actinic keratosis (AK), thyroid cancer, breast cancer, glioma and hepatic cancer, as well as explore the potential underlying pathogenesis. Methods: We conducted a bidirectional two‐sample Mendelian randomization study to probe the potential causal relationships between rosacea and several types of cancer. Instrumental variables were established using genome‐wide significant single nucleotide polymorphisms associated with rosacea and cancers. The assessment of causality was carried out through multiple methods, and the robustness of the results was evaluated via sensitivity analyses. Results: There was no significant indication of causal effects of rosacea on CMM ( p _ivw = 0.71), cSCC ( p _ivw = 0.45), BCC ( p _ivw  = 0.90), AK ( p _ivw = 0.73), thyroid cancer ( p _ivw = 0.59), glioma ( p _ivw = 0.15), and hepatic cancer ( p _ivw  = 0.07), but the genetic risk of rosacea was associated with an increased susceptibility to human epidermal growth factor receptor (HER)‐negative malignant neoplasm of breast (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02–1.18; p _ivw = 0.01). TANK (TRAF family member associated nuclear factor kappa B (NFKB) activator) was identified as a common protective gene for both rosacea (OR, 0.90; 95% CI, 0.82–0.99; p _ivw = 0.048) and HER‐negative malignant neoplasm of the breast (OR, 0.86; 95% CI, 0.75–0.98; p _ivw = 0.032), which was primarily enriched in the negative regulation of NF‐κB signal transduction and may contribute to the genetic links between rosacea and this subtype of breast cancer. Conclusions: Our findings provide suggestive evidence for causal links between rosacea and HER‐negative malignant neoplasm of the breast risk.

Rosacea is a prevalent skin disorder in which neurogenic inflammation plays a significant role in its pathogenesis. Gabapentin (GBP) has garnered attention as a therapeutic option; however, its precise mechanism of action in treating rosacea remains unclear. Through a comprehensive analysis of experimental and clinical data, the research team has elucidated the molecular mechanism by which GBP inhibits neurogenic inflammation, particularly through modulating the NF-κB signaling pathway to alleviate rosacea inflammation. Using a murine rosacea model induced by LL37, the efficacy of GBP was compared to Minocycline and Hydroxychloroquine combination therapy. Various techniques assessed marker expression, transcriptomic profiles, and in vitro cell experiments with BV2 cells. Clinical data from 60 rosacea patients were analyzed through a randomized trial, comparing GBP therapy to the combination treatment. Results showed GBP effectively reduced skin inflammation and facial redness in mice and patients. Metabolomic analysis indicated significant changes in metabolites post-GBP treatment, correlating with inflammatory factors. The study concludes that GBP mitigates rosacea progression by targeting neurogenic inflammation via NF-κB pathway regulation, shedding light on novel treatment mechanisms through transcriptomics and metabolomics for future clinical application in rosacea research.

Pemphigus vulgaris (PV) is an autoimmune skin disorder characterized by the loss of cell cohesion, with the histone deacetylase 1 (HDAC1) and lysine demethylase 1A (KDM1A) playing critical roles in its pathogenesis. This study aimed to elucidate the molecular mechanisms behind PV, focusing on the function of HDAC1 and KDM1A in disease onset and progression. Based on in vitro and in vivo PV models, we observed a significant increase in HDAC1 mRNA and protein levels in skin tissues of PV patients. Inhibition of HDAC1 ameliorated cell damage and reduced the loss of cell cohesion in human epidermal keratinocytes (HEKs) induced by PV-IgG. Our findings suggest that HDAC1 regulates KDM1A expression through deacetylation, with a notable deficiency in KDM1A expression in PV. Overexpression of KDM1A mitigated cell damage and cohesion loss. The extracellular signal-regulated kinase (ERK) pathway serves as a downstream executor of the HDAC1/KDM1A axis. Inhibiting HDAC1 and increasing KDM1A expression suppressed ERK phosphorylation, reducing PV-related apoptosis. These insights provide a new perspective on treating PV, highlighting the therapeutic potential of targeting HDAC1 expression. The regulatory mechanism of the HDAC1/KDM1A/ERK axis offers crucial clues for understanding PV pathogenesis and developing novel treatments.