Search

Breast cancer stem cells (CSC), as a kind of tumor cells, are able to regenerate themselves, leading to apoptosis resistance and cancer relapse. In this study, we investigated the potential of Hyptis Capitata and Hyptis Brevipes compounds in preventing apoptosis resistance and inducing targeted cell cycle arrest in CSC. The cytotoxic effects of the compounds were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and the cell cycle distribution and apoptosis induction were assessed through flow cytometry analysis. The phytochemical characterization of Hyptis bravipes extract (HBE) and Hyptis capitata extract (HCE) conducted under thin layer chromatography (TLC) and highperformance liquid chromatography (HPLC) analysis. The results revealed that Hyptis Brevipes extract (HBE) exhibited strong cytotoxicity towards CSCs, with an IC50 value of 89 µg/mL. In contrast, Hyptis Capitata extract (HCE) showed weak growth inhibition, with an IC50 value greater than 500 µg/mL. Subsequent analysis demonstrated that HBE induced cell cycle arrest in the G2/M and S phases and significantly increased apoptosis in the CSC population. Furthermore, phytochemical characterization using TLC and HPLC revealed that HBE and HCE share similar constituent compounds, with HBE exhibiting a more diverse compound content and stronger cytotoxic effects. These findings provide valuable insights into the potential of Hyptis Capitata and Hyptis Brevipes compounds as targeted agents against breast cancer stem cells and contribute to understanding their chemical profiles and pharmacological properties. [ABSTRACT FROM AUTHOR]

Background: Severe third-degree burns pose a notable obstacle in clinical settings, frequently leading to hindered healing of wounds and the development of scars. In this research, we explored how the secretome of hypoxic mesenchymal stem cells (HS-MSCs) could be improved the healing of burn wounds. Methods: In this study, we used 20 male Wistar rats that induced third degree wound by metal 80 exposure for 10 s. These rats divided into 4 groups: Healthy, control, HS-MSCs 100 µL, and HS-MSCs 200 µL groups. We injected the HS-MSCs, which carry various beneficial molecules like IL-10, TGF-β, PDGF, and VEGF, directly into the skin in a third-degree burn rat model on day 1 after burn induction, and harvest on day 14. Results: Our research discovered that using HS-MSCs resulted in a dosage-related rise in IL-10, an anti-inflammatory cytokine, alongside a notable decrease in TNF-α and PGE2, pro-inflammatory cytokines. These effects quickened the healing process by improving re-epithelialization and minimizing scar formation. Conclusions: Our findings indicate that HS-MSCs show promise as a treatment for severe burns by potentially controlling inflammation and fostering a regenerative healing process. More investigation is needed to understand the exact mechanisms and to explore how HS-MSCs could be applied in clinical treatments. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) has become a global health challenge with several associated issues, such as obesity, insulin resistance, dyslipidemia, and hypertension. Important proteins such as Tumor Necrosis Factoralpha (TNF-α) and Hypoxia Inducible Factor-2 alpha (HIF-2α) regulate the inflammatory process by inducing the expression of pro-inflammatory proteins. This study aims to determine the effect of administering SH-MSCSs on the expression of the TNF-α and Hypoxia Inducible Factor (HIF)-2α genes in the male Wistar rat model with Metabolic Syndrome. This research is an experimental study with a Post-test Only Control Group Design, using a total of 24 male Wistar rats divided into four groups: T1 (Healthy control), T2 (MetS + NaCl), T3 (MetS + administration of SH-MSCs dose 150 uL), and T4 (MetS + administration of SH-MSCs dose 300 uL). SH-MSCSs were administered intraperitoneally four times over 14 days. Adipose tissue TNF-α and HIF-2α gene expression were measured on day 15 using qRT-PCR. TNF-α and HIF-2α gene expression was significantly lower in T3 and T4, compared with the MetS control group (T2). Administration of SH-MSCs was able to reduce the expression of the Tumor Necrosis Factor (TNF-α) and Hypoxia Inducible Factor (HIF)-2α genes in fatty tissue in the male Wistar rat model with Metabolic Syndrome. This study presents a novel approach to treating MetS by demonstrating that the administration of SH-MSCs significantly reduces the expression of pro-inflammatory genes TNF-α and HIF-2α. This finding is beneficial for society as it suggests a potential new therapeutic strategy that could mitigate inflammation and improve health outcomes for individuals suffering from MetS, thereby addressing a critical global health challenge. [ABSTRACT FROM AUTHOR]

Background: Lead exposure inflicts severe damage to various body organs. The present study sought to assess the effect of chitosan nanoparticles (NPs) on the prevention of hepatic and renal damage in rats with chronic lead poisoning. The indicators were the levels of oxidative stress and proinflammatory cytokines expression. Methods: We used Rattus norvegicus as the animal model. They were assigned to three groups: negative control, positive control, and treatment (n=8 each). The negative control and treatment groups were the models for chronic lead poisoning, and the serum lead levels were determined by atomic absorption spectrometry. The treatment group was orally administered chitosan NPs at 64 mg/kg for 30 days. The reactive oxygen species (ROS) were measured using 2',7'-dichlorodihydrofluorescein diacetate flow cytometry. The hepatic and renal TNF-α and IL-6 gene expressions were also analyzed. Results: The mean serum lead level was 0.52 mg/L, validating the rats as the lead poisoning model. The results indicated that the liver and kidneys in the treatment group had the lowest ROS and TNF-α levels compared to those in other groups. The treatment rats had a lower hepatic IL-6 level compared to those in positive controls, although this was higher than that in the negative controls. The renal IL-6 level in the treatment group was the highest among all groups. Conclusion: As evidenced by the results of this study, chitosan NPs had a protective effect on the liver and kidneys of rats during chronic lead poisoning by reducing the ROS and TNF-α levels; nonetheless, it did not suppress the renal IL-6 expression. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus (T2DM) is a prevalent form of diabetes that affects 90 - 95 % of all diabetic patients. Insulin sensitizers and insulin exogenous supply could temporarily ameliorate hyperglycaemia; however, they are accompanied by side effects. As a result, new approaches are required to address insulin resistance and regenerate beta cells simultaneously. The secretome of hypoxic mesenchymal stem cells (SH-MSCs) contains various growth factors and anti-inflammatory cytokines that could potentially enhance insulin resistance and improve pancreatic function. Objectives: In this study, we performed SH-MSCs infusion to ameliorate HFD-induced hyperglycaemia in T2DM rats. Methods: We created a T2DM rat model using a combination of a high-fat diet (HFD) and streptozotocin (STZ) administration. Then, we administered SH-MSCs injection at doses of 250 and 500 µL and assessed the therapeutic effects of SH-MSCs. We also investigated the potential underlying mechanisms involved. Results: The administration of SH-MSCs improved hyperglycemia in rats with T2DM. Infusion of SH- MSCs at 500 µL dose decreased homeostatic model assessment for insulin resistance (HOMA-IR). Histological analysis revealed that injection of SH-MSCs alleviated morphological damage of pancreas. SH-MSCs administration also inhibit the level of IL-6 and promote the expression of CD163 type 2 macrophage. Conclusion: The results of our study indicate that SH-MSCs have the potential to improve hyperglycemia and exert a protective effect on T2DM rats. [ABSTRACT FROM AUTHOR]

Chronic lead exposure induces ROS accumulation which causes physiological disorders. Chelation therapy has been widely used to overcome lead poisoning since it exerts only a few side effects. Nano chitosan prevents lead poisoning by inhibiting ROS. This study examined the pharmacokinetics of nano chitosan in chronic lead-induced toxicity animal models and the mechanism of action pathway using the bioinformatic approach, The area under the curve was estimated to be 12110.13 ± 7709.37 µg/mL hours using the pharmacokinetic model, and the Cmax was 82.34 ± 5.64 µg/mL. The Tmax and t½ calculations were 22.68 ± 11.67 and 80.47 ± 60.58 hours respectively. Chitosan nanoparticles regulated VEGFA, FGF2, and LGALS3 which plausibly played a substantial role in chronic lead exposure. However, chitosan is not suitable for oral administration due to its low gastrointestinal solubility. These characteristics make chitosan nanoparticles have the prospect of being developed as a supplement so that they can contribute to overcoming the negative impacts of chronic lead poisoning. [ABSTRACT FROM AUTHOR]

Background and purpose: Highly metastatic breast cancer is a population of cancer cells that has metastasized to other organs in the body leading to apoptosis resistance. It was reported that MDAMB-231 cells contain lower levels of reactive oxygen species associated with metastatic capability. Curcuma longa (CL) possesses cytotoxic effects in several cancer cells including metastatic breast cancer cells. This study aimed to investigate the effect of CL-inhibited cell migration in highly metastatic breast cancer MDAMB-231 cells. Experimental approach: CL was extracted under maceration with methanol. The cytotoxic effect on single and combination treatment of CL was assessed through the MTT assay. Migration analysis was evaluated using scratch wound healing assay, MMP-9 expression by gelatine zymography, Rac-1, and MMP-9 gene expression using Real-Time Quantitative Reverse transcription polymerase chain reaction (qRT-PCR). The apoptosis induction was analyzed through Bax gene expression and Bcl-2 protein expression. Findings/Results: We found that CL inhibits the growth of MDAMB-231 cells, induces Bax gene expression, and suppresses Bcl-2 expression in a dose-dependent manner. Moreover, cancer cell migration was suppressed by the presence of CL. qRT-PCR and gelatine zymography assay showed that CL downregulates Rac-1 and MMP-9 gene expression. Conclusion and implications: CL could inhibit the growth and migration of highly metastatic breast cancer cells by reducing the Rac-1 gene expression and regulating apoptosis protein expression. [ABSTRACT FROM AUTHOR]

Background: We previously reported that in highly metastatic breast cancer cells, doxorubicin (DOX) at non-toxic concentrations promoted cell migration and invasion. Hesperidin (30, 5, 9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavonoid glycoside isolated from citrus/lemon plant that possesses a cytotoxic effect in several cancer cells. In this study, we investigate whether DOX efficacy is enhanced by hesperidin (Hsd) and the molecular pathway involved in highly metastatic breast cancer, 4T1. Methods: Combined cytotoxicity of Hsd and DOX was evaluated with MTT assay and was analyzed using Chou-Talalay's method. To better understand the underlying mechanism, several factors, including apoptosis and cell cycle arrest were analyzed by flow cytometry. In addition, antimigration activity was evaluated by scratch wound healing assay, MMP-9 expression by ELISA and gelatin zymography, and Rac-1 protein level using western blot. The data on survival rate and expression level of MMP-9 and Rac-1 were obtained from Gene Expression OMNIBUS (GEO). Results: Under MTT assay, Hsd showed a cytotoxic effect in a concentration-dependent manner with an IC50 value of 284 µM on 4T1 cells. Hsd synergistically enhanced the cytotoxic effect of DOX which seemed to correlate with an increase in apoptotic cell death, G2/M cell cycle arrest and blocked the migration of 4T1 cells. At 10 nM, doxorubicin induced lamellipodia formation, and increased the level of Rac-1 and metalloproteinase-9 (MMP-9) expression. Interestingly, combined treatment of DOX and Hsd dramatically downregulated the expression of MMP-9 and Rac-1. These results indicated that Hsd block the cell migration induced by DOX under in vitro studies. Conclusion: These findings strongly suggest that Hsd possesses a potential synergistic effect that can be developed to enhance the anticancer efficacy of DOX and reduce the risks of chemotherapy use in highly metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Genistein, a soy isoflavone, exhibits a biphasic effect on cells proliferation with some different effects between ER-alpha and ER-beta. The objective of this present study is to determine the modulatory effect based on cell cycle progression under genistein treatment in combination with 17-β estradiol (E2) on CHO-K1 cells. Methods: The effect of genistein 0.1-100 μM on cells proliferation was examined by MTT assay. The modulation of genistein and estradiol (E2) on cell cycle and apoptosis were observed by using flowcytometry with PI and PI/AnnexinV staining, respectively. Moreover, the effect of genistein and E2 on senescence cells, and ROS level were determined by senescence-associated β-galactosidase (SA β-gal) staining and by using flowcytometry with 2’, 7’–dichlorofluorescin diacetate (DCFDA) staining, respectively. The expression level of the cell cycle and senescence protein markers were observed by immunoblotting. Results: Single treatment of genistein at physiologically achievable (low) concentration (<2 μM) induced proliferation of CHO-K1 cells while at a pharmacological (high) concentration (50 and 100 μM) suppressed cells proliferation. Interestingly, treatment of genistein at the physiological concentration in combination with E2 for 24, 48 and 72 h decreased cells viability on CHO-K1 cells compared to untreated cells. Further analysis of the cells showed that 50 μM genistein induced G2/M phase accumulation and induced apoptosis. Moreover, genistein induced cell senescence and increased ROS level. Immunoblotting analysis showed the decreasing of ERalpha, Bcl2, and ppRb protein level upon treatment of 1 μM Gen and 1 nM E2. Conclusion: Our results suggest that the cell proliferation inhibitory mechanism of genistein at pharmacological concentration involved the induction of cell senescence, and the elevation of ROS level. Moreover, the decreased of cells proliferation upon treatment of physiological concentration of genistein in combination with E2 may be correlated with the alteration of ER expression. [ABSTRACT FROM AUTHOR]