An in vitro investigation of the apoptosis-inducing activity of corosolic acid in breast cancer cells.

Objectives: Breast cancer is the most prevalent cancer among females with different molecular subtypes. Corosolic acid is a pentacyclic triterpenoid with anti-cancer properties. Materials and Methods: The MTT assay was used to assess the cytotoxic activity of corosolic acid on MDA-MB-231 and MCF7 cell lines. To determine the apoptotic cells, the flow cytometry technique was utilized. The expression levels of apoptosis-related genes and proteins were quantified using quantitative real time-PCR (qRT-PCR) and Western blotting methods. The activity of caspase enzymes was measured by spectrophotometry. Results: Corosolic acid significantly inhibited the proliferation of both cell lines compared with controls. This agent markedly induced apoptosis in MDA-MB-231 cells but did not affect MCF7 cells compared with controls. Treating the MADA-MB-231 and MCF7 cell lines with corosolic acid showed an inducing effect on apoptosis-associated caspases, including Caspase-8, 9, and -3, in MADA-MB-231 cells with no effect on apoptotic markers in MCF7 cells. Further experiments uncovered corosolic acid-induced apoptosis in MADA-MB-231 cells by decreasing the expression of the phosphorylated form of JAK2 and STAT3 proteins. Conclusion: The present data suggested that corosolic acid is an apoptosis-inducing phytochemical in triple-negative breast cancer MADA-MB-231 cells. Also, corosolic acid triggered apoptosis in these cells by stimulating both pathways of apoptosis and inhibiting the JAK/STAT signaling. Furthermore, corosolic acid was found to inhibit MCF7 cell proliferation by a non-apoptotic mechanism.

Apigenin alleviates resistance to doxorubicin in breast cancer cells by acting on the JAK/STAT signaling pathway.

BACKGROUND: Breast cancer is the most frequent cancer among women. Despite the effectiveness of Doxorubicin (DOX) as a chemotherapeutic for the treatment of breast cancer, the therapy-resistance remains unsolvable. Apigenin is a natural dietary flavonoid with potential anticancer activities. Our study's intention was to evaluate the effect of Apigenin on DOX resistance in MCF-7 cells. METHODS: DOX-resistant MCF-7 cell line (MCF-7R) was developed by treating MCF-7 cells with increasing concentrations of DOX (0-100 µM). The viability of cell lines was assayed using MTT method. Quantitative polymerase chain reaction method was performed to measure multidrug-resistance 1 (MDR1) gene expression level. The expression of MDR1, Janus kinase 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3) proteins were determined by western blotting. RESULTS: MCF-7R cell line showed resistance to DOX in comparison to MCF-7 cells. Apigenin had a significant effect on the reduction of viability of both MCF-7 and MCF-7R cell lines. However, DOX-resistance in the MCF-7 cell line was considerably decreased due to the co-treatment of MCF-7R cells with Apigenin. This natural compound also downregulated the expression of MDR1 at mRNA and protein levels both in resistant and non-resistant cells. Apigenin significantly prohibited the phosphorylation and activation of JAK2 and STAT3 proteins both in MCF-7 and MCF-7R cell lines. CONCLUSIONS: The present results suggested, for the first time, Apigenin as an ideal therapeutic for ameliorating DOX resistance in breast cancer. These data also proposed a novel mechanism for the anti-resistance activity of Apigenin by regulating the JAK2/STAT3/MDR1 axis.

Exposure to ambient air pollution and osteoarthritis; an animal study.

Exposure to air pollution has been associated with many adverse health effects. However, the evidence on the effects on osteoarthritis (OA) is scarce and the potential mechanism is unclear yet. Therefore, this study assessed the effect of exposure to air pollution (gaseous and particulate matter) and OA based on an animal model. We used four groups of female rats, including i) exposure to PMs and gaseous pollutants, ii) exposure only to gaseous pollutants, iii) exposure only to PMs, and iv) control (unexposed) group. The OA biomarkers, i.e., osteocalcin, cartilage oligomeric protein (COMP), and N-Telopeptides of Type I Collagen (NTX-I) and cytokines were measured in the plasma to detect the effect of exposure to ambient air pollution on OA in this animal model. The forced jogging exercises for 1 h and 5 days per week were used to record the physical activities. The median (interquartile range) concentrations of PM2.5 and PM10 were 35.9 (15.4) and 47.5 (22.5) µg/m3, respectively. The median (interquartile range (IQR)) of PM2.5, PM10, CO, NO2, SO2 and O3 in the inlet ambient air were 36.9 (16.9), 51.7 (23.6) µg/m3, 16.1 (12.5) ppm, 413.7 (177.1), 334.2 (218.8) and 208.9 (113.1) ppb, respectively. The osteocalcin was significantly lower in PM as well as PM-gaseous exposure groups compared to control. Moreover, expressions of COMP were increased significantly in the PMs and exposure group compared to the control. For the PMs-gaseous exposure group, the COMP expressions were the highest compared to the control group. Similar results were observed for NTX-I. Exposure to PM and gaseous pollutants significantly increased plasma cytokine levels compared to control. Overall, our study showed a significant effect of exposure to PMs and PMs-gaseous exposure with OA in rats. Moreover, we observed a synergistic effect of mixed gaseous-PMs exposure compared to PMs and gaseous pollutants separately.

Cloning and Embryo Splitting in Mammalians: Brief History, Methods, and Achievements.

Embryo splitting is one of the newest developed methods in reproductive biotechnology. In this method, after splitting embryos in 2-, 4-, and even 8-cell stages, every single blastomere can be developed separately, but the embryos are genetically identical. Embryo splitting, as an approach in reproductive cloning, is extensively employed in reproductive medicine studies, such as investigating human diseases, treating sterility, embryo donation, and gene therapy. In the present study, cloning in mammalians and cloning approaches are briefly reviewed. In addition, embryo splitting and the methods commonly used in embryo splitting and recent achievements in this field, as well as the applications of embryo splitting into livestock species, primate animals, and humans, are outlined. Finally, a perspective of embryo splitting is provided as the conclusion.

MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy.

Currently, mesenchymal stem/stromal stem cell (MSC) therapy has become a promising option for accelerating cutaneous wound healing. In vivo reports have outlined the robust competences of MSCs to offer a solid milieu by inhibition of inflammatory reactions, which in turn, enables skin regeneration. Further, due to their great potential to stimulate angiogenesis and also facilitate matrix remodeling, MSCs hold substantial potential as future therapeutic strategies in this context. The MSCs-induced wound healing is thought to mainly rely on the secretion of a myriad of paracrine factors in addition to their direct differentiation to skin-resident cells. Besides, MSCs-derived exosomes as nanoscale and closed membrane vesicles have recently been suggested as an effective and cell-free approach to support skin regeneration, circumventing the concerns respecting direct application of MSCs. The MSCs-derived exosomes comprise molecular components including lipid, proteins, DNA, microRNA, and also mRNA, which target molecular pathways and also biological activities in recipient cells (e.g., endothelial cell, keratinocyte, and fibroblast). The secreted exosome modifies macrophage activation, stimulates angiogenesis, and instigates keratinocytes and dermal fibroblast proliferations as well as migrations concurrently regulate inherent potential of myofibroblast for adjustment of turnover of the ECM. In the present review, we will focus on the recent findings concerning the application of MSCs and their derivative exosome to support wound healing and skin regeneration, with special focus on last decade in vivo reports.

Re-Expression of Poly/Oligo-Sialylated Adhesion Molecules on the Surface of Tumor Cells Disrupts Their Interaction with Immune-Effector Cells and Contributes to Pathophysiological Immune Escape.

Glycans linked to surface proteins are the most complex biological macromolecules that play an active role in various cellular mechanisms. This diversity is the basis of cell-cell interaction and communication, cell growth, cell migration, as well as co-stimulatory or inhibitory signaling. Our review describes the importance of neuraminic acid and its derivatives as recognition elements, which are located at the outermost positions of carbohydrate chains linked to specific glycoproteins or glycolipids. Tumor cells, especially from solid tumors, mask themselves by re-expression of hypersialylated neural cell adhesion molecule (NCAM), neuropilin-2 (NRP-2), or synaptic cell adhesion molecule 1 (SynCAM 1) in order to protect themselves against the cytotoxic attack of the also highly sialylated immune effector cells. More particularly, we focus on α-2,8-linked polysialic acid chains, which characterize carrier glycoproteins such as NCAM, NRP-2, or SynCam-1. This characteristic property correlates with an aggressive clinical phenotype and endows them with multiple roles in biological processes that underlie all steps of cancer progression, including regulation of cell-cell and/or cell-extracellular matrix interactions, as well as increased proliferation, migration, reduced apoptosis rate of tumor cells, angiogenesis, and metastasis. Specifically, re-expression of poly/oligo-sialylated adhesion molecules on the surface of tumor cells disrupts their interaction with immune-effector cells and contributes to pathophysiological immune escape. Further, sialylated glycoproteins induce immunoregulatory cytokines and growth factors through interactions with sialic acid-binding immunoglobulin-like lectins. We describe the processes, which modulate the interaction between sialylated carrier glycoproteins and their ligands, and illustrate that sialic acids could be targets of novel therapeutic strategies for treatment of cancer and immune diseases.

A comprehensive review of histopathological findings of infections induced by COVID-19.

The severe acute respiratory syndrome (SARS)-Coronavirus (CoV2) virus, first identified in Wuhan, China, caused the coronavirus disease 2019 (COVID-19) which soon became a global pandemic, as labelled by the World Health Organization (WHO). The transmission method of the infection is primarily through droplets of various sizes. The SARS-CoV2 virus leads to a severe respiratory illness which in the first place causes the simulation of the acute respiratory syndrome. In order to diagnose of COVID-19 efficiently, samples with infection probability need to be examined through histopathological methods. Survival chances of the infected can remarkably increase if the virus is diagnosed timely by reverse transcription-polymerase chain reaction (RT-PCR) or computed tomography (CT) scan of the chest. One of the destructive effects of COVID-19 is the formation of ground-glass opacity (GGO) in the lungs which might be regarded to be equivalent to high-altitude pulmonary edema (HAPE). COVID-19 acts very similarly to SARS and Middle East Respiratory Syndrome (MERS) which can be inactivated by the chemical compounds of ethanol and sodium hypochlorite. Epidemiologic characteristics of COVID-19 have been indicated by numerous studies; however, there is still a lack of details of pathologic changes in the lung. The present comprehensive review is an attempt to assess and cover the current state of knowledge on COVID-19 disease based on the histopathologic studies conducted before May 2020.