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Over recent years, much attention has been devoted to the field of screening natural products and/or their novel structures because of reversing cancer progression. The current research work was intended to explore the cytotoxic activity of ethanol and ethyl acetate extracts of dried fruit of Terminalia chebula Retz. (T. chebula) in MCF-7 cell line. High-performance thin-layer chromatographic (HPTLC) method and Folin-Ciocalteu colorimetric techniques were performed. Anti-proliferative activities of T. chebula fruit extracts on the MCF-7 cell line were evaluated using MTT assay. Effects of both extracts on the migration of MCF-7 cells and the size of MCF-7-derived spheroids were also evaluated. Moreover, antioxidant properties were measured by DPPH and FRAP methods. Western blotting was used to measure the HIF-1α and CXCR-4 protein levels. Chebulagic acid, gallic acid, chebulinic acid, and ellagic acid were found as major compounds in both extracts. The total phenolic contents based on gallic acid equivalent (GAE) in the ethanol and ethyl acetate extracts of T. chebula were found to be 453.68 ± 0.31 and 495.12 ± 0.43 mg GAE/g dry weight of the extract, respectively. Both extracts exerted a significant dose- and time-dependent cytotoxicity effect on MCF-7 cells. They also had a marked negative effect on the average size of MCF-7-derived spheroids and their migration rate. None of the extracts exhibited stronger antioxidant activities than vitamin C. Furthermore, both extracts at a concentration of 125 µg/ml could meaningfully decrease the expression levels of HIF-1α and CXCR-4 in MCF-7 cells. These data represent that T. chebula may be a valuable medicinal resource in the regulation of breast cancer proliferation, growth, and metastasis.

Long non-coding RNAs (lncRNAs) have a critical role in the regulation of cardiovascular function. Dysregulation of lncRNAs is implicated in the progression of cardiovascular diseases including myocardial infarction (MI). Regarding the beneficial effects of exercise (Ex) on the improvement of MI, this study aimed to investigate the effects of post-MI Ex on the expression of MI-associated lncRNAs: H19, myocardial infarction association transcript (MIAT), and growth arrest specific 5 (GAS5). MI was induced by left anterior descending (LAD) coronary artery ligation in male Wistar rats. One week later, rats were exercised under a moderate-intensity protocol for 4 weeks. In the end, hemodynamic parameters and cardiac function indices were measured. Assessment of fibrotic areas and apoptosis was performed by Masson's trichrome staining and immunohistochemistry, respectively. Expression of genes was evaluated by real-time PCR. Ex significantly reduced the fibrotic areas (P

Nowadays, metal-organic frameworks (MOFs) have emerged as promising tools for different biological applications and therefore, efforts are ongoing to develop more biocompatible MOFs-based nanocomposites. We aimed to fabricate some new conductive nanocomposites of polypyrrole and cobalt-MOF with different weight percentages (PPy/x%Co-MOF) using the solution mixing method and characterize them through FT-IR (Fourier-transform infrared), PXRD (powder X-ray diffraction), SEM (scanning electron microscope), and TEM (transmission electron microscope) techniques. The biocompatibility of nanocomposites was assessed by haemolytic, cytotoxic, and quantitative reverse transcription PCR (qRT-PCR) assays. FT-IR and PXRD results revealed that nanocomposites consisted of pure MOFs and PPy. Moreover, SEM results indicated their spherical morphology along with an average diameter of 190 nm. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed a concentration, and percentagedependent cytotoxic effect of the nanocomposites on some cell lines including 3T3 fibroblasts, MCF-7, and J774.A1 macrophages. Haematological toxicity of PPy/x%Co-MOF composites was less than 7% in most concentrations. Furthermore, PPy/x%Co-MOF composites did not show any significant effect on the expression of cyclooxygenase-2( COX-2) and inducible nitric oxide synthase( iNOS) genes. In sum, regarding the haemolytic, proinflammatory, and cytotoxic tests, prepared nanocomposite demonstrated the reasonable in vitro biocompatibility which may be considered as a hopeful platform for further investigations including clinical applications.

Hypomyelinating leukodystrophy type 2 (HLD2), is an inherited genetic disease of the central nervous system caused by recessive mutations in the gap junction protein gamma 2 (GJC2/GJA12). HLD2 is characterized by nystagmus, developmental delay, motor impairments, ataxia, severe speech problem, and hypomyelination in the brain. The GJC2 sequence encodes connexin 47 protein (Cx47). Connexins are a group of membrane proteins that oligomerize to construct gap junctions protein. In the present study, a novel missense mutation gene c.760G>A (p.Val254Met) was identified in a patient with HLD2 by performing whole exome sequencing. Following the discovery of the new mutation in the proband, we used Sanger sequencing to analyze his affected sibling and parents. Sanger sequencing verified homozygosity of the mutation in the proband and his affected sibling. The autosomal recessive inheritance pattern was confirmed since Sanger sequencing revealed both healthy parents were heterozygous for the mutation. PolyPhen2, SIFT, PROVEAN, and CADD were used to evaluate the function prediction scores of detected mutations. Cx47 is essential for oligodendrocyte function, including adequate myelination and myelin maintenance in humans. Novel mutation p.Val254Met is located in the second extracellular domain of Cx47, both extracellular loops are highly conserved and probably induce intramolecular disulfide interactions. This novel mutation in the Cx47 gene causes oligodendrocyte dysfunction and HLD2 disorder.

The most common complication of pregnancy is idiopathic recurrent pregnancy loss (RPL). To identify the contribution of gene polymorphisms to this condition, we evaluated the association between RPL and the angiotensinogen (