Exposure to per- and polyfluoroalkyl substances and bone health: a systematic review and meta-analysis.

Perfluoroalkyl substances (PFAS) as a large group of synthetic compounds widely contaminated the environment and lead to health problems. However, the correlation between PFAS exposure, bone health parameters and osteoporosis remains controversial. Therefore, we conducted a systematic review and meta-analysis of published literature to evaluate the effects of PFAS on human bone health. All observational studies were collected up to 2 December 2023. A total of 2096 articles were retrieved. Of these, 21 articles investigated the association between PFAS exposure and human bone health. However, only 10 studies were included in the final meta-analysis. Doubling of serum perfluorooctanoic acid (PFOA) (ß = -0.11, 95% confidence interval (CI): -0.18, -0.05) and perfluorooctane sulfonic acid (PFOS) (ß = -0.06, 95% CI: -0.11, -0.01) levels showed significant negative correlations with total body less head bone mineral density (TBLH-BMD). Subgrouping showed that only perfluorohexane sulfonate (PFHxS) (odds ratio [OR] = 1.37, 95% CI: 1.12, 1.68) was correlated with osteoporosis.

MiR-1236: Key controller of tumor development and progression: Focus on the biological functions and molecular mechanisms.

Combating with the cancer, as one of the leading causes of morbidity and mortality worldwide, scientific community extensively evidenced microRNA 1236 (miR-1236) roles in the pathogenesis of malignant tumors. It has been mentioned that miR-1236 target genes and signal pathways that are key controller of tumor development and progression. Consistently, increasing evidence reports that miR-1236 participates in cancer cell growth, migration, invasion, apoptosis, and drug resistance, as well as tumor diagnosis, and prognosis. MiR-1236 is also implicated in epithelial-mesenchymal transition (EMT), which is a significant indicator of the metastatic process. Moreover, miR-1236 itself is regulated by several newly discovered long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Current review aimed to summarize and discuss different dimensions of miR-1236 involvement in the fundamental cellular and molecular mechanisms of tumor progressions. We believe that miR-1236 may serve as a non-invasive diagnostic marker and potential therapeutic target for cancer.

A3 receptor agonist, Cl-IBMECA, potentiate glucose-induced insulin secretion from MIN6 insulinoma cells possibly through transient Ca2+ entry.

Diabetes incidence showed ascending trends in recent years indicating urgent need for new therapeutic agents. Extracellular adenosine signaling showed promising results. However, role of its A3 receptor in pancreatic ß-cells proliferation and insulin secretion is not well established. Thus, we aimed to determine its main signaling mediators in MIN6 insulinoma cell line. A3 adenosine receptor (A3AR) expression was confirmed using RT-PCR. Receptor functionality was evaluated by measurements of cAMP, using ELISA kit, and intracellular Ca2+ levels, using Fura 2/AM probe in response to the specific A3AR agonist (Cl- IBMECA). Insulin ELISA kit was used to measure insulin release. Herein, we mentioned that MIN6 cells express active form of A3AR, which decreased cAMP levels with the half maximal effective concentration (EC50) value of 5.61. [Ca2+]i Levels transiently (approximately 120 sec) increased in response to the agonist. Cl-IBMECA increase insulin secretion at 0.01-1 µM, but showed an inhibitory effects at higher concentrations (1-10 µM). Altogether, we found that in MIN6 cells, A3AR, possibly through Ca2+ mediated signaling pathways, potentiated glucose-induced insulin secretion.

Centaurea cyanus extracted 13-O-acetylsolstitialin A decrease Bax/Bcl-2 ratio and expression of cyclin D1/Cdk-4 to induce apoptosis and cell cycle arrest in MCF-7 and MDA-MB-231 breast cancer cell lines.

Natural products are considered recently as one of the source for production of efficient therapeutical agents for breast cancer treatment. In this study, a sesquiterpene lactone, 13-O-acetylsolstitialin A (13ASA), isolated from Centaurea cyanus, showed cytotoxic activities against MCF-7 and MDA-MB-231 breast cancer cell lines using standard 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To find the mechanism of action of cytotoxicity, annexin V/propidium iodide (PI) staining was performed for evaluation of apoptosis. This process was further confirmed by immunoblotting of anti- and proapoptotic, Bcl-2 and Bax, proteins. Cell cycle arrest was evaluated by measurement of fluorescence intensity of PI dye and further confirmed by immunoblotting of Cdk-4 and cyclin D1. Mitochondrial transmembrane potential (ΔΨm) and generation of reactive oxygen species (ROS) were measured using the JC-1 and DCFDA fluorescence probes, respectively. These experiments showed that 13ASA is a potent cytotoxic agent, which activates apoptosis-mediated cell death. In response to this compound, Bax/Bcl-2 ratio was noticeably increased in MCF-7 and MDA-MB-231 cells. Moreover, 13ASA induced cell cycle arrest at subG1 and G1 phases by decreasing protein levels of cyclin D1 and Cdk-4. It was done possibly through the decrease of ΔΨm and increase of ROS levels which induce apoptosis. In conclusion, this study mentioned that 13ASA inhibit the growth of MCF-7 and MDA-MB-231 breast cancer cell lines through the induction of cell cycle arrest, which triggers apoptotic pathways. 13ASA can be considered as a susceptible compound for further investigation in breast cancer study.

Jatropha-6(17),11E-diene class derivatives induce apoptosis effects in OVCAR-3 and Caov-4 ovarian cancer cell lines via a mitochondrial pathway.

We investigated the molecular mechanism of apoptosis induced by novel jatropha-6(17),11E-diene class derivatives, compounds A, B, and C that were extracted from Euphorbia osyridea Boiss, in the ovarian cancer cell lines Caov-4 and OVCAR-3. The OVCAR-3 and Caov-4 cell lines were treated with different concentrations of these compounds. Cytotoxicity was evaluated using MTT, clonogenic survival assay, and flow cytometry assays. The production of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and the activity of caspase 3 and 9 were evaluated. Compounds A, B, and C reduced cell viability in a dose-dependent manner (P < 0.05). The IC50 values were calculated as 46.27 ± 3.86, and 38.81 ± 3.30 µmol/L for compound A, 36.48 ± 3.18 and 42.59 ± 4.50 µmol/L for compound B, and 85.86 ± 6.75 and 75.65 ± 2.56 µmol/L for compound C against the Caov-4 and OVCAR-3 cell lines, respectively. Apoptosis evaluation showed that jatrophane derivatives increase both early and late apoptosis (P < 0.01). These compounds also increased ROS generation, ΔΨm, and the activity of caspase 3 and 9 in the treated cells. These results showed that compounds A and B have significant inhibitory effects on OVCAR-3 and Caov-4 proliferation and induction of apoptosis.