The promotive role of lncRNA MIR205HG in proliferation, invasion, and migration of melanoma cells via the JMJD2C/ALKBH5 axis.

Melanoma is a highly malignant skin cancer. This study aimed to investigate the role of long non-coding RNA MIR205 host gene (lncRNA MIR205HG) in proliferation, invasion, and migration of melanoma cells via jumonji domain containing 2C (JMJD2C) and ALKB homolog 5 (ALKBH5). Real-time quantitative polymerase chain reaction or Western blot assay showed that MIR205HG, JMJD2C, and ALKBH5 were increased in melanoma cell lines. Cell counting kit-8, colony formation, and Transwell assays showed that silencing MIR205HG inhibited proliferation, invasion, and migration of melanoma cells. RNA immunoprecipitation, actinomycin D treatment, and chromatin immunoprecipitation showed that MIR205HG may bind to human antigen R (HuR, ELAVL1) and stabilized JMJD2C expression, and JMJD2C may increase the enrichment of H3K9me3 in the ALKBH5 promotor region to promote ALKBH5 transcription. The tumor xenograft assay based on subcutaneous injection of sh-MIR205HG-treated melanoma cells showed that silencing MIR205HG suppressed tumor growth and reduced Ki67 positive rate by inactivating the JMJD2C/ALKBH5 axis. Generally, MIR205HG facilitated proliferation, invasion, and migration of melanoma cells through HuR-mediated stabilization of JMJD2C and increasing ALKBH5 transcription by erasing H3K9me3.

Efficacy and Safety of a Novel Plum Blossom Needling with Mild Moxibustion Device for Upper Limb Pain Disorder and Motor Dysfunction in Patients with Stage 1 Post-Stroke Shoulder-Hand Syndrome: Study Protocol for a Multi-Center, Single-Blind, Randomized Sham-Controlled Trial.

Background: Post-stroke shoulder-hand syndrome (PS-SHS), a common neurological comorbidity after stroke episodes, poses a grave threat on patients' functional recovery. Preliminary trials have demonstrated that the acupuncture and moxibustion treatment, including a dermal acupuncture tapping method known as plum blossom needling (PBN) can improve pain and motor dysfunctions in patients with PS-SHS. However, there are few reports describing simultaneous moxibustion treatment in combination with PBN. Hence, a novel plum blossom needle device with mild moxibustion (PBNMM) was developed to evaluate its potential efficacy and safety in patients with stage 1 PS-SHS. Materials and Methods: This multicenter, sham-controlled, randomized controlled trial (RCT) will recruit 102 eligible patients with stage 1 PS-SHS from three clinical centers, randomly allocated in a ratio of 1:1:1 to the PBNMM group, PBNMM with no moxa smoke (PBNMM-NMS) group and sham control group. Patients in each group will receive a 30-minute treatment once per day for 4 weeks, with 5 consecutive sessions per week, for a total of 20 sessions. The primary outcome measure will be defined as the decreased scores from baseline in the visual analog scale (VAS) assessment at week 4. Secondary outcome measures will include scores on the Fugl-Meyer Assessment of the Upper Extremity Scale (FMA-UE), the Modified Barthel Index (MBI), and the somatosensory evoked potential (SEP) records. All outcomes will be evaluated at baseline and weeks 4, 5, 6 and 10, and the intention-to-treat analysis will be applied. Conclusion: This study aims to provide robust evidence for the efficacy and safety of the PBNMM for PS-SHS treatment, as well as the specific impact of moxibustion smoke itself in dealing with PS-SHS. Clinical Trial Registration: Chinese Clinical Trial Registry No. ChiCTR2200062441. Registered on 7 August 2022.

miR-20a Overexpression in Adipose-Derived Mesenchymal Stem Cells Promotes Therapeutic Efficacy in Murine Lupus Nephritis by Regulating Autophagy.

OBJECTIVE: Lupus nephritis is the most common and severe complication of systemic lupus erythematosus. The aim of our study was to investigate the efficacy of miR-20a overexpressing adipose-derived stem cell (ADSC) transplantation in murine lupus nephritis (LN) and explore potential molecular mechanisms. METHODS: Mouse ADSCs were transfected with a miR-20a lentiviral vector to obtain miR-20a overexpression ADSCs (miR-20a-ADSCs). We first observed the influence of miR-20a on ADSC viability and apoptosis in vitro. B6.MRL/lpr mice were administered ADSC/miR-20a-ADSC intravenously every week from age 30 to 33 weeks, and the lupus and normal control groups received PBS on the same schedule. RESULTS: miR-20a expression increased in miR-20a-ADSC-derived exosomes, and miR-20a overexpression promoted ADSC proliferation and inhibited apoptosis. Compared with ADSCs, miR-20a-ADSC treatment significantly improved serologic and histologic abnormalities, as evidenced by reduced serum creatinine, anti-dsDNA antibody, 24 h urine protein levels, nephritis scores, and C3/IgG deposits. Furthermore, miR-20a-ADSC treatment resulted in downregulated Akt, mTOR, and p62 expression and upregulated miR-20a, Beclin 1, and LC3 II/I expression compared with ADSC treatment. After treatment with miR-20a-ADSC, a significant increase in the number of autophagosomes within podocytes was observed, along with upregulated expression of podocin and nephrin, compared with the ADSC group. CONCLUSIONS: miR-20a-ADSC transplantation prevents the development of lupus nephritis and significantly ameliorates already-established disease, and its mechanism is related to autophagy by targeting the miR-20a-regulated mTOR pathway.

Decreased TMEM40 expression is associated with malignant behavior of cutaneous squamous cell carcinoma and inhibits tumor progression.

Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer in humans worldwide. The identification and characterization of cancer-associated transmembrane proteins are important for understanding the molecular biology of CSCC. The aim of the present study was to evaluate the expression pattern of transmembrane protein 40 (TMEM40) in CSCC and its clinical significance. The underlying mechanisms were also examined. Reverse transcription-quantitative PCR, western blot and immunohistochemistry analysis were used to determine the relative expression of TMEM40 in CSCC cell lines and clinical tissue samples. The effect of TMEM40 gene silencing on cell proliferation was also evaluated using Cell Counting Kit-8 assays. Wound healing assays, flow cytometry and Transwell assays were used to explore the migration, cell cycle distribution/apoptosis and invasion of CSCC cells following TMEM40 silencing, respectively. In the present study, increased TMEM40 expression was observed in CSCC tissue samples, compared with normal skin, and TMEM40 expression was associated with large tumor size in patients with CSCC. In vitro functional assays indicated that TMEM40 was involved in the regulation of A431 and SCL1 cell growth through its effects on the cell cycle and apoptosis. Silencing TMEM40 in A431 and SCL1 cells resulted in cell cycle arrest at the G0/G1 phase and promoted apoptosis. In addition, migration and invasion were significantly inhibited following silencing of TMEM40 expression in CSCC cells. Taken together, the results of the present study indicated that reduced TMEM40 expression could inhibit CSCC development and that TMEM40 may represent a therapeutic target in CSCC.

CHILD Syndrome: Case Report of a Chinese Patient and Literature Review of the NAD[P]H Steroid Dehydrogenase-Like Protein Gene Mutation.

Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) syndrome is an X-linked autosomal dominant disorder characterized by unilateral congenital hemidysplasia with ichthyosiform erythroderma and ipsilateral limb defects caused by a mutation in the gene encoding NAD[P]H steroid dehydrogenase-like protein (NSDHL) at Xq28. The histopathologic hallmark of skin lesions in CHILD syndrome is psoriasiform epidermis with hyperkeratosis and parakeratosis, and its most striking feature affecting the upper dermis is filling of the papillary dermis with foam cells. Here we present the case of a 9-year-old Chinese girl born with the typical clinical features of CHILD syndrome. Histologic and immunohistochemical evaluation of the skin lesions confirmed the diagnosis and led to identification of a heterozygous point mutation in exon 8 of the NSDHL gene. In addition, we provide a literature review of 26 unrelated CHILD syndrome patients from different countries, caused by 20 unique gene mutations occurring throughout the entire NSDHL gene, to promote understanding and provide a more comprehensive description of this unusual disorder.

[Investigation of selective inhibition of digoxin derivative on retinoic acid-related orphan nuclear receptor γt transcription activity using molecular docking].

OBJECTIVE: Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity. METHOD: Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORß and RORγt), and the results were further confirmed by bioluminescent assay. RESULT: Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner. CONCLUSION: Dhd can selectively suppress RORγt transcriptional activity.