Downregulation of BIRC2 hinders the progression of rheumatoid arthritis through regulating TRADD.

AIM: Rheumatoid arthritis (RA) is a chronic inflammation mediated by an autoimmune response. Baculoviral IAP repeat-containing 2 (BIRC2) and tumor necrosis factor receptor 1-associated death domain protein (TRADD) have been reported to be highly expressed in RA, while their specific roles during RA progression remain unclear. This study aims to explore the specific regulation of BIRC2/TRADD during the progression of RA. METHODS: C28/I2 cells were stimulated by lipopolysaccharide (LPS) to establish an in vitro RA cellular model. The expression level of BIRC2 and TRADD was examined by quantitative real-time polymerase chain reaction and western blot. Cell Counting Kit-8 and flow cytometry assays were performed to examine cell viability and necroptosis, respectively. The oxidative stress markers were detected using commercial kits, and the pro-inflammatory cytokines were measured by ELISA assay. The interaction between BIRC2 and TRADD was verified by co-immunoprecipitation assay. RESULTS: BIRC2 and TRADD were discovered to be highly expressed in LPS-mediated C28/I2 cells. BIRC2 knockdown was demonstrated to inhibit LPS-induced cell viability loss, necroptosis, oxidative stress, and inflammation in C28/I2 cells. BIRC2 could interact with TRADD and positively regulate TRADD expression. In addition, the protective role of BIRC2 knockdown against LPS-mediated injuries in C28/I2 cells was partly weakened by TRADD overexpression. CONCLUSION: In summary, BIRC2 knockdown alleviated necroptosis, oxidative stress, and inflammation in LPS-mediated C28/I2 cells, which might correlate to the regulatory role of TRADD, indicating a novel target for the treatment of RA.

Comparison of the efficacy of seven types of microneedles for treating a rabbit hypertrophic scar model.

Microneedle technology can effectively suppress the formation of hypertrophic scarring in both animals and humans. Our previous research has revealed that this is due to the physical contact inhibition effect by using microneedles made of liquid-crystal polymers as the model device. One important factor we didn't study is the influence of the fabrication materials of microneedles. Therefore, this article examines this key point on a rabbit ear hypertrophic scar model. We monitor the thickness of the scars, and the expression of α-SMA and Ki-67 protein, and TGF-ß1 mRNA in a period of 42 days. Among microneedles made of 6 polymeric materials and stainless steel, polymethylmethacrylate microneedles present superiority in all aspects including the reduction of tissue fibrosis, and the expression of α-SMA, Ki-67 protein and TGF-ß1 mRNA. On the other hand, polycarbonates, polyurethane, and polylactic-co-glycolic acid microneedles could suppress three biomarker expressions.

PP2Acα regulates epidermal cell proliferation via the EGFR/AKT/mTOR pathway in psoriasis-like skin lesions caused by PPP2CA deficiency.

Psoriasis, a common skin disease, endangers human physiological and mental health; however, its pathogenesis remains unclear. Keratinocyte proliferation is a typical pathological characteristic of psoriasis. Serine/threonine protein phosphatase 2A (PP2A) is one of the most important phosphatases for maintaining normal phosphorylation levels in humans. PP2Acα is the alpha subtype of the PP2A C subunit (encoded by PPP2CA), which maintains the catalytic functions of PP2A. Epidermal growth factor receptor (EGFR) is activated by phosphorylation (p-EGFR) to regulate the downstream signalling pathway to promote epidermal cell proliferation. Previous studies have found that PPP2CA induced epidermal hyperplasia, keratinization and other pathological phenomena similar to those in mouse models of psoriasis. The present study showed that PP2Acα negatively regulated EGFR phosphorylation and epidermal cell proliferation, and EGFR inhibitors could alleviate PP2Acα by inhibiting epidermal cell proliferation. This study further examined the effect of mechanisms on epidermal cell proliferation and the downstream signalling pathway of EGFR using molecular technological methods to explore new ideas for treating psoriasis.

MiR-424 Functions as Potential Diagnostic and Prognostic Biomarker in Melanoma.

BACKGROUND: Melanoma is one of the most aggressive and lethal skin cancers worldwide. To our knowledge, no specific or sensitive biomarkers have been clinically used to diagnose or predict melanoma prognosis. MicroRNAs (miRNAs) have been shown to regulate oncogenesis and tumor development in various cancers including melanoma. The aim of present study was to determine the clinical value of miR-424 in melanoma. METHODS: First, we examined the expression levels of miR-424 in tissue and serum samples of melanoma patients using real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Then, receiver operating characteristic curves were used to determine the diagnostic value of miR-424. Furthermore, the chi-square test was used to analyze the relationship between the expression of miR-424 and the clinical characteristics of the patients. Finally, the Kaplan-Meier survival analysis was applied to validate the prognostic value of miR-424 in melanoma. RESULTS: The results demonstrated that miR-424 expression was remarkably increased in tissues and serum of pa-tients with melanoma. Moreover, results of ROC analysis showed both tissue and serum expression of miR-424 can serve as diagnostic biomarker for melanoma. Meanwhile, miR-424 expression was significantly associated with tumor thickness (p = 0.031), metastasis (p = 0.010) and tumor stage (p = 0.005) and ulceration (p < 0.001). Finally, patients with higher miR-424 expression have shown decreased overall survival and disease-free survival than those with low miR-424 expression, implying that high miR-424 expression will contribute to poor prognosis of melanoma. CONCLUSIONS: MiR-424 may function as a diagnostic and prognostic biomarker for melanoma.

Photodynamic therapy for basal cell carcinoma of external auditory canal: A case report.

BACKGROUND: Basal cell carcinoma (BCC) that occurs in the external auditory canal (EAC) is rare. Currently reported cases are mainly treated with surgical resection. Here, we described an early-detected BCC of the EAC, which achieved good results with photodynamic therapy (PDT). METHODS: 5-aminolevulinic acid (5-ALA) solution was applied on the tumor and its surrounding area of 0.5 cm normal skin. The skin lesion was encapsulated with sterile plastic film and covered with black film to avoid light. Then a special semiconductor laser fiber with 635 nm wavelength red light was directly inserted into the EAC to irradiate the lesion. RESULTS: The wound was healed. After 1 year of follow-up, there was no recurrence of the tumor. CONCLUSION: Our case shows that PDT for BCC of the EAC can also achieve good results. It adds a new treatment option for BCC of EAC patients, especially for those who cannot or refuse to use surgery.