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Objective: Breast cancer (BC) is the most common cancer in women and the second leading cause of cancer-related deaths. MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression post-transcriptionally and play a central role in the dysregulation of gene expression associated with carcinogenesis, cancer cell proliferation and metastasis. Twist1 is a transcription factor that binds to E-box motifs and controls the transcriptional activity of genes as a positive or negative regulator decisive in the cellular mechanisms. Accordingly, Twist1 also regulates the expression of miRNAs that are associated with cancer progression. In present study, we aimed to investigate the expressional changes of possible miRNAs directly regulated by Twist1 in triple negative breast cancer MDA-MB-231 cells. Materials and Methods: In this study, a total of 43 miRNA genes were evaluated that predicted might be associated with triple negative breast cancer. To determine the Twist1-targeted miRNA genes, endogenous high level Twist1 expression was suppressed through the antisense oligonucleotides in MDA-MB-231 TNBC cells. Differential miRNA expression levels were analyzed by real time PCR analysis in Twist1-suppressed cells compare to control. Results: Twist1 suppression leads to an increase in miR-1-1 and miR-210-3p expression, while a decrease in miR-193b-3p, miR-181b-5p, and miR-148a-3p expression. Conclusion: This study shows that the expression levels of certain miRNAs linked to invasion, metastasis, and apoptosis are controlled by Twist1 in triple negative breast cancer cells.

Background This study aimed to investigate the effects of Lopinavir/Ritonavir (Lop/r) on chondrocyte structure and extracellular matrix (ECM) integrity, as well as its impact on key proteins involved in anabolic and catabolic pathways, using both in vitro and in silico approaches. Methods Drug-target interaction networks were constructed through bioinformatics analyses, and molecular docking was performed. Human primary chondrocytes were treated with Lop/r, and untreated cells served as controls. Cell viability, proliferation, and protein expression levels were assessed using standard in vitro techniques, including spectrophotometric assays and Western blotting. Results Molecular docking analyses revealed strong binding affinities between Lop/r and osteoarthritis-related targets such as HIF-1α, EP300, TNF, IL-6, KCNA5, and IL-1β, suggesting modulation of hypoxia, inflammatory, and epigenetic pathways. In vitro, Lop/r did not alter chondrocyte morphology or ECM structure and was not cytotoxic ( p  < 0.05). However, it significantly reduced the expression of critical proteins including HIF-1α, SOX9, and IL-1β ( p  < 0.05). Conclusion These findings suggest that Lop/r may exert regulatory effects on cartilage-related molecular pathways and holds promise as a repurposed therapeutic agent for osteoarthritis. Further studies are warranted to confirm its potential in clinical applications.

This study aimed to produce zinc oxide nanoparticles with Calendula officinalis flower extract (Co‐ZnO NPs) using the green synthesis method. In addition, the antioxidant and wound healing potential of synthesized ZnO NPs were evaluated. The absorbance band at 355 nm, which is typical for ZnO NPs, was determined from the UV–Vis absorbance spectrum. The energy‐dispersive X‐ray spectroscopy (EDS) measurements revealed a high zinc content of 42.90%. The x‐ray diffractometer data showed Co‐ZnO NPs with an average crystallite size of 17.66 nm. The Co‐ZnO NPs did not have apparent cytotoxicity up to 10 μg/mL (IC50 25.96 μg/mL). C. officinalis ZnO NPs showed partial cell migration and percent wound closure (69.1%) compared with control (64.8%). In addition, antioxidant activities of Co‐ZnO NPs with 2,2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and 2,2 diphenyl‐1 picrylhydrazil (DPPH) were evaluated and radical scavenging activity of 33.49% and 46.63%, respectively, was determined. These results suggest that C. officinalis extract is an effective reducing agent for the green synthesis of ZnO NPs with significant antioxidant and wound healing potential.

Osteoarthritis is a progressive degenerative joint disorder characterised by cartilage degradation and chronic inflammation. Beyond their well‐established lipid‐lowering properties, statins, particularly pitavastatin and rosuvastatin, have demonstrated promising anti‐inflammatory and chondroprotective effects. This study comprehensively evaluated these effects on human primary chondrocytes using an integrative approach involving in silico and in vitro experiments. Key molecular targets, including NF‐κB, IL‐1β and SOX9, were analysed to elucidate the mechanisms underlying the therapeutic potential of these statins. Molecular docking analyses using the CB‐Dock2 platform revealed strong binding affinities of both statins with the target proteins, with pitavastatin exhibiting a higher binding score (−8.0) compared to rosuvastatin (−7.9). Bioinformatics analyses via STITCH and STRING databases highlighted the involvement of both statins in pathways regulating inflammation, lipid metabolism, and cartilage homeostasis. In vitro experiments demonstrated that both statins preserved chondrocyte viability at 24 and 48 h; however, prolonged exposure led to significant declines, with rosuvastatin exhibiting greater cytotoxicity. Western blot analyses confirmed that both statins effectively suppressed IL‐1β expression, indicative of potent anti‐inflammatory activity. Pitavastatin transiently enhanced SOX9 expression, peaking at 24 h before declining, while rosuvastatin showed a more sustained but moderate increase. NF‐κB expression steadily increased over time with both statins, suggesting potential activation of compensatory inflammatory pathways during prolonged exposure. These findings underscore the dual anti‐inflammatory and chondroprotective roles of pitavastatin and rosuvastatin, while highlighting the need for careful consideration of dosage and treatment duration to mitigate cytotoxic effects and provide novel insights into the molecular mechanisms of statins.

Alzheimer’s disease (AD), especially its sporadic form (sAD), is of multifactorial nature. Brain insulin resistance and disrupted zinc homeostasis are two key aspects of AD that remain to be elucidated. Here, we investigated the effects of dietary zinc deficiency and supplementation on memory, hippocampal synaptic plasticity, and insulin signaling in intracerebroventricular streptozotocin (icv-STZ)-induced sAD in rats. The memory performance was evaluated by Morris water maze. The expression of hippocampal protein and mRNA levels of targets related to synaptic plasticity and insulin pathway was assessed by Western blot and real-time quantitative PCR. We found memory deficits in icv-STZ rats, which were fully recovered by zinc supplementation. Western blot analysis revealed that icv-STZ treatment significantly reduced hippocampal PSD95 and p-GSK3β, and zinc supplementation restored the normal protein levels. mRNA levels of BDNF, PSD95, SIRT1, GLUT4, insulin receptor, and ZnT3 were found to be reduced by icv-STZ and reestablished by zinc supplementation. Our data suggest that zinc supplementation improves cognitive deficits and rescues the decline in key molecular targets of synaptic plasticity and insulin signaling in hippocampus caused by icv-STZ induced sAD in rats.

Abstract The aim of this study was to evaluate the anticancer effects of biosynthesized silver nanoparticles (Vv-AgNPs) from grape (Vitis vinifera L.) seed aqueous extract, alone or in combination with 5-Fluorouracil (5-FU) on HT-29 cell line. Vv-AgNPs were characterized by techniques such as UV–vis spectrophotometer (surface plasmon peak 454 nm), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). HT-29 cells were treated with different concentrations (0–80 μg/mL for MTT) and (0–20 μg/mL for BrdU) of Vv-AgNPs alone and combined with (200 μg/mL) 5-FU for 72 h. The cytotoxic effects were analyzed by [3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay (IC50 values 13.74 and 5.35 μg/mL, respectively). Antiproliferative effects were examined 5-bromo-2'-deoxyuridine (BrdU) assay (IC50 values 9.65 and 5.00 μg/mL, respectively). Activation of caspase-3 and protein expression levels of p53 were determined by Western blotting analysis. It was observed that Vv-AgNPs significantly increased the cleavage of the proapoptotic proteins caspase 3 and obviously enhanced the expression of p53 in a dose-dependent manner. The increased amount of total oxidant status (TOS) in the 10 μg/mL Vv-AgNPs + 5-FU treatment group, despite the increasing amount of total antioxidant status (TAS), caused an increase in Oxidative Stress Index (OSI) compared to the control. In this study, it has been shown in vitro that the use of successfully biosynthesized Vv-AgNPs in combination with 5-FU exhibits synergistic cytotoxic, antiproliferative, apoptotic, and oxidative effects against HT-29 cell line.

This study aimed to investigate the effects of Lopinavir/Ritonavir (Lop/r) on chondrocyte structure and extracellular matrix (ECM) integrity, as well as its impact on key proteins involved in anabolic and catabolic pathways, using both in vitro and in silico approaches. Drug-target interaction networks were constructed through bioinformatics analyses, and molecular docking was performed. Human primary chondrocytes were treated with Lop/r, and untreated cells served as controls. Cell viability, proliferation, and protein expression levels were assessed using standard in vitro techniques, including spectrophotometric assays and Western blotting. Molecular docking analyses revealed strong binding affinities between Lop/r and osteoarthritis-related targets such as HIF-1[alpha], EP300, TNF, IL-6, KCNA5, and IL-1[beta], suggesting modulation of hypoxia, inflammatory, and epigenetic pathways. In vitro, Lop/r did not alter chondrocyte morphology or ECM structure and was not cytotoxic (p < 0.05). However, it significantly reduced the expression of critical proteins including HIF-1[alpha], SOX9, and IL-1[beta] (p < 0.05). These findings suggest that Lop/r may exert regulatory effects on cartilage-related molecular pathways and holds promise as a repurposed therapeutic agent for osteoarthritis. Further studies are warranted to confirm its potential in clinical applications.

Purpose The purpose of the present study is to understand Twist-related protein 1 (Twist1) spatiotemporal expression patterns and functions during early embryo development. Methods We performed whole-mount double immunofluorescence staining and reverse transcription (RT)-PCR analysis of the Twist1 protein and gene throughout the preimplantation development in mice. Results We determined that after compaction, the expression of Twist1 becomes developmentally differentiated and targeted in the inner cells of embryos. In blastocysts at E4.5, uniform staining of the inner cell mass was apparent, and it had been gradually translocated to the nucleus of hatched embryonic cells at E4.75. Furthermore, the effect of potential regulators of Twist on its expression level during blastocyst development was also sought. Accordingly, Twist1 expression appeared to be upregulated in both mRNA and protein level following culture of embryos in the presence of high glucose. Conclusions Our study revealed the dynamic Twist localization within the early stage of embryo. The results are discussed in terms of potential roles of Twist1 in the processes of lineage segregation, hatching, and implantation in post-compaction embryos and in blastocysts.

Reprogramming of glucose metabolism in cancer cells triggers tumor development. Most cancer cells provide the energy needed from aerobic glycolysis called the \"Warburg effect\" to promote uncontrolled proliferation and invasion. Therefore, direct regulator molecules of aerobic glycolysis remain active research targets. Epithelial mesenchymal transition (EMT) is the main mechanism that promotes cancer invasion and poor prognosis. One of the key effector molecules of the EMT is TWIST1. In this study, we sought to investigate the role that TWIST1 has in driving glycolytic programming and cellular energy charges in 293T cells by overexpressing TWIST1 in 293T cells. Plasmid vectors were successfully transfected by lipofectamine 2000 and mRNA expressions of interested genes were assessed. Glucose, lactate and pH levels of culture supernatants were determined by radiometer analyzer. The cellular energy charge of the cells were calculated from ATP, ADP and AMP data analyzed by HPLC. Here, we found that TWIST1 transcription factor, which has highly conserved sequences, is an important regulator for aerobic glycolysis. We found that TWIST1 increases the expression of glycolytic genes such as HK2, PKM2, LDH a, PFKM and G6PD, the production of lactate and extracellular acidification in 293T cells. We have also determined that TWIST1 promotes aerobic glycolysis metabolism by providing cellular energy exchange. TWIST1 overexpression reduced AMP/ATP and ADP/ATP ratios in 293T cells, with further increase seen in ATP production. By this work, we confirmed that TWIST1 is closely related to the glycolysis pathway and is an important regulator of the Warburg effect.