miRNA Let-7a-5p targets RNA KCNQ1OT1 and Participates in Osteoblast Differentiation to Improve the Development of Osteoporosis.

It is known that miRNA mediates the formation of osteogenesis, but the mechanism by which miRNA let-7a-5p regulates osteogenesis in osteoporosis (OP) is not yet understood. This paper aims to probe into the regulatory mechanism of miRNA let-7a-5p in the development of OP. Fresh femoral trabecular bones of patients with osteoporotic fracture (OP group, n = 25) and non-OP osteoarthritis (Non-OP group, n = 23) who underwent hip replacement in our hospital from December 2016 to December 2019 were collected. The expression and protein levels of miRNA let-7a-5p and V-AKT murine thymoma viral oncogene homolog 3 (RNA KCNQ1OT1) were detected. C2C12 cells were purchased and osteogenic differentiation model was constructed by BMP2 induction. After miRNA let-7a-5p up-regulation or down-regulation by transfection of corresponding mimics and inhibitors, the impacts of miRNA let-7a-5p and RNA KCNQ1OT1 on osteogenic differentiation-related factors (OC, ALP, COL1A1) in C2C12 cells were analyzed. The determination of targeting correlation of miRNA let-7a-5p with RNA KCNQ1OT1 was performed by dual-luciferase reporter (DLR). In OP samples, miRNA let-7a-5p was notably declined while RNA KCNQ1OT1 were remarkably up-regulated. MiRNA let-7a-5p reduced in C2C12 cells as BMP2 treatment proceeded. MiRNA let-7a-5p up-regulation or RNA KCNQ1OT1 down-regulation increased OC, ALP, COL1A1 levels and ALP activity. RNA KCNQ1OT1 was directly targeted to miR-497-5p. RNA KCNQ1OT1 up-regulation weakened the promoting effect of miRNA let-7a-5p up-regulation on osteoblast differentiation. MiRNA let-7a-5p up-regulation can target to reduce RNA KCNQ1OT1 and promote osteoblast differentiation, thereby improving the development of osteoporosis.

Evaluation on Efficacy of Psychological and Behavioral Intercession and Its Implications on People with Schizophrenia: A Novel Approach.

OBJECTIVE: To examine and evaluate the efficacy of the spectrum of psychological and behavioral intercession as a novel treatment regime to address the necessity of Schizophrenia affected patients. METHOD: A sum of 148 individuals with the first episode of Schizophrenia enrolled in the trial. Patients admitted in our medium-sized hospital with symptoms of schizophrenia were scrutinized carefully and selected for the intercession trial. Total selected individuals were bifurcated into two groups based on guidelines prescribed in the intervention model. Control group or standard care group (SCG) was treated with usual medications and nursing measures of psychiatry practices. Experimental Group (EG) was conferred with enriched psychological strategy and behavioral modules to tackle and satisfy their specific needs. Various methods such as positive and negative syndrome scale (PANSS), several disability screening schedule (SDGSS), satisfaction with life scale (SWLS), global assessment scale (GAS) and finally rate of recurrence of disease were evaluated and analyzed. RESULTS: Efficacy of psychological and behavioral intercession on psychotic domine is proved to be effective, and a novel strategy and it is significantly reducing positive and negative psychological symptoms in the experimental group was observed attributing to the intercession. Moreover, a drastic attenuation in the rate of recurrence of disease was supporting a long term efficiency of intercession. CONCLUSION: Conducting intervention on psychological and behavioral approach has explored novel treatment outcomes, targeted schizophrenia patients effectively.

MiR-624-5p enhances NLRP3 augmented gemcitabine resistance via EMT/IL-1ß/Wnt/ß-catenin signaling pathway in ovarian cancer.

The current study investigates the NLRP3's cytotoxicity inhibitory effect among ovarian cancer cells and how it interacts with Wnt/ß-catenin in vitro conditions. Further, the study also analyzed the regulatory role of NLRP3 in resistance to gemcitabine among ovarian cancer cells and its underlying interaction mechanisms with Wnt/ß-catenin in vitro. The current in vitro study detailed that when downregulating NLRP3, it could enhance the gemcitabine sensitivity in GRC cells. In case of gemcitabine-resistant cells, the up-regulation of NLRP3 can increase the drug-resistance through the activation of IL-1ß, EMT and Wnt/ß-catenin signaling pathways. High expression of miR-624-5p was recorded in ovarian drug resistant cancer cells and it also boosted the cell viabilities. NLRP3 can reinstate the functioning of miR-624-5p in drug resistant cells. This phenomenon concludes that NLRP3 is a promising therapeutic target and can be implemented in traditional chemotherapy to increase the efficacy of the treatment. The current study conducted in vitro experiments and the findings infer that the downregulation of NLRP3 can enhance the sensitivity of gemcitabine among GRC cells. This mechanism will increase the treatment efficacy by inhibiting the drug resistance in GRC. These two entities are the new promising biomarkers that can be used in the detection of platinum resistance in ovarian cancer patients and conduct novel clinical research.

Detection of Novel Biallelic Causative Variants in COL7A1 Gene by Whole-Exome Sequencing, Resulting in Congenital Recessive Dystrophic Epidermolysis Bullosa in Three Unrelated Families.

Background: Dystrophic Epidermolysis bullosa (DEB) is a rare, severe subtype of epidermolysis bullosa (EB), characterized by blisters and miliary rashes of the skin. Dystrophic EB (DEB) includes variants inherited both in an autosomal-dominant or autosomal-recessive manner. Recessive dystrophic EB (RDEB) is divided into many subtypes and prevails as a result of biallelic genetic mutations in COL7A1 gene encoding type VII collagen, a major stabilizing molecule of the dermo-epidermal junction. The blister formation is mainly due to the variable structural and functional impairment of anchoring fibrils in VII collagen (COLVII), responsible for the adhesion of the epidermis to the dermis. Method: Three Pakistani families (A, B and C) affected with congenital dystrophic epidermolysis bullosa were recruited in the present study. The whole-exome sequencing (WES) approach was utilized for the detection of the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing. Results: This study identified a novel missense variant c.7034G>A, p. Gly2345Asp in exon 91, a novel Frameshift mutation c.385del (p. His129MetfsTer18) in a homozygous form in exon no 3, and a previously known nonsense variation (c.1573 C>T; p. Arg525Ter) in exon 12 of COL7A1 gene in families A, B, and C, respectively, as causative mutations responsible for dystrophic epidermolysis bullosa in these families. Conclusion: Our study validates the involvement of the COL7A1 gene in the etiology of dystrophic epidermolysis bullosa. It further expands the COL7A1 gene mutation database and provides an additional scientific basis for diagnosis, genetic counseling, and prognosis purposes for EB patients.

Differential expression of miR-130a-3p modulate ovarian epithelial carcinoma (OEC) cell development and could be a biomarker for OEC.

A lot of research investigations, conducted in the recent years, establishes that microRNAs (miRNAs) have an important role in keeping both growth and metastasis of Ovarian Epithelial Carcinoma (OEC) under control. However, the clinical and functional role of miR-130a-3p in OEC is yet to be explored. Through quantitative reaction i.e., qRT-PCR, the expression of miR-130a-3p was assessed in tissues and cell lines of OEC patients. This analysis determined the relationship between the expression of miR-130a-3p and its clinicopathology with the overall survival rate of OEC patients. The author made use of cell counting analysis (CCK8) and in vitro flow cytometry to understand the functional and biological impact of miR-130a-3p expression. In comparison with neighboring normal tissues, the expression of miR-130a-3p was found to be lower in 7 OEC samples. Few reasons are cited for this scenario i.e., low expression of miR-130a-3p, such as low overall OEC patient survival rate, incidence of FIGO and metastasis of lymph nodes. miR-130a-3p has been found as an independent candidate for predicting the prognosis of OEC patients, as per Multivariate Cox research. When miR-130a-3p is over-expressed, as per the enhanced mechanism, it prevents both cell proliferation and cell cycle production in OEC. The current study findings emphasize that miR-130a-3p can be leveraged as a biomarker of prognosis and possibly as a target in the treatment of OEC.