Protective roles of some natural and synthetic aromatase inhibitors in testicular insufficiency caused by Bisphenol A exposure.

In our study, the protective role of synthetic aromatase inhibitors anastrozole (ANS), letrozole (LTZ) and exemestane (EXM) and natural aromatase inhibitors resveratrol (RSV) and apigenin (APG) against testicular failure caused by exposure to Bisphenol A (BPA) was investigated. The epididymal sperm concentration, sperm motility and sperm morphology were determined. Oxidative stress and inflammatory response parameters were examined and histological examinations were performed in testicular tissues. Our results revealed that BPA exposure decreased serum testosterone and estrogen levels, increased FSH and LH levels (p < 0.05). BPA has been found to increase oxidative stress and inflammatory response and disrupt the histological structure. Also, BPA exposure decreased testicular weight, epididymal sperm concentration and motility, and increased abnormal sperm rate (p < 0.05). These results show that ANS, LTZ and RSV treatments reduce the BPA-induced testicular damage.

Investigation of the impact of antiparasitic drug moxidectin on the rewarding effects of alcohol.

Alcohol addiction or alcoholism constitutes a significant risk factor worldwide for morbidity and mortality. Moxidectin is a recently approved anthelmintic drug, which also activates the gamma-aminobutyric acid receptors. The objective of the present study was to examine the impact of moxidectin on rewarding effects of ethanol in the conditioned place preference (CPP) model in mice. In separate experiments, mice were administered intraperitoneal (i.p.) injections of moxidectin (5 or 10 mg/kg, i.p.) before a) acquisition of alcohol-induced CPP, b) each extinction session, and c) alcohol-induced reinstatement of CPP. The present experiments provide consistent data about ethanol place preference in mice (2 g/kg, i.p.), with mice in all tests spending significantly more time on the ethanol-paired side. The acquisition of the CPP response to ethanol was prevented by the administration of moxidectin at a dose of 10 mg/kg. Additionally, moxidectin treatment accelerated the extinction of ethanol CPP when given repeatedly during the extinction phase. Ethanol-induced reinstatement of CPP following an extinction phase was inhibited by moxidectin. Ethanol alone and co-administration with moxidectin did not change locomotor activity and motor coordination. In conclusion, we suggest that moxidectin may be a promising therapeutic candidate for prevention of ethanol-induced addiction and relapse as well as detoxification.

Roe protein hydrolysate of Alburnus tarichi induces apoptosis in breast cancer MCF-7 and MDA-MB-231 cells through a caspase-dependent pathway.

The protein hydrolysates of fishes have been reported to be a potential source of many health benefits components for pharmaceutical or nutritional applications. The aim of this study is to examine the possible antiproliferative function of roe protein hydrolysates of Alburnus tarichi using enzymatic hydrolysis against breast cancer cells and explore its detailed mechanisms. In addition, we evaluated the effects of protein hydrolysate on the proliferation and apoptosis of two human breast cancer cell lines (MCF-7 and MDA-MB-231). The cultured cells were treated with protein hydrolysate at concentrations of 0-5 µg/ml for 24 h and 48 h. Inhibition of cell proliferation, percentage of apoptotic cells, cell cycle distribution, morphological changes, DNA fragmentation, intracellular reactive oxygen species (ROS) production, and apoptotic protein levels were also examined. Decreases in proliferation of MCF-7 and MDA-MB-231 cells were observed after treatment with the protein hydrolysate in a dose-dependent manner. Distinct morphological changes, a typical pattern of fragmented DNA, and increased intracellular ROS production and apoptotic protein levels were observed in both cell lines after hydrolysate treatment (p < 0.05). The results suggested that the protein hydrolysate inhibits the proliferation of human breast cancer cell lines by introducing apoptosis through a caspase-dependent pathway in a dose-dependent manner.

Inflammatory Markers as Predictors of Atrial Fibrillation Recurrence: Exploring the C-Reactive Protein to Albumin Ratio in Cryoablation Patients.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac rhythm disorder associated with hemodynamic disruptions and thromboembolic events. While antiarrhythmic drugs are often recommended as the initial treatment, catheter ablation has emerged as a viable alternative. However, the recurrence of AF following ablation remains a challenge, and there is growing interest in exploring inflammatory markers as predictors of recurrence. METHODS: This retrospective, cross-sectional analysis included 249 patients who underwent cryoablation for paroxysmal AF. The relationship between the 'C-reactive protein (CRP) to albumin ratio (CAR)' and AF recurrence was examined. RESULTS: Two hundred and forty-nine patients with paroxysmal non-valvular atrial fibrillation were included. They were divided into two groups: those without recurrence (Group 1) and those with recurrence (Group 2). Significant differences were observed in age (57.2 ± 9.9 vs. 62.5 ± 8.4, p = 0.001) and left atrial size (4.0 ± 0.5 vs. 4.2 ± 0.7, p = 0.001) between the two groups. In blood parameters, significant differences were found in CRP (5.2 ± 1.3 vs. 9.4 ± 2.8, p < 0.001) and neutrophil counts (5.1 ± 2.2 vs. 6.7 ± 3.6, p = 0.001). In univariate regression analysis, age (OR: 1.058, CI: 1.024-1.093, p = 0.001), WBC count (OR: 1.201, CI: 1.092-1.322, p < 0.001), neutrophil count (OR: 1.239, CI: 1.114-1.378, p = 0.001), CAR (OR: 1.409, CI: 1.183-1.678, p < 0.001), and left atrial diameter (OR: 0.968, CI: 0.948-0.989, p = 0.002) showed significant associations with AF recurrence. CONCLUSIONS: Inflammation plays a crucial role in the initiation and progression of AF. This study demonstrated that along with age, the CAR can serve as an independent predictor of AF recurrence following cryoablation.

Artesunate inhibits melanoma progression in vitro via suppressing STAT3 signaling pathway.

BACKGROUND: Melanoma is a life-threatening cancer characterized with a potentially metastatic tumor of melanocytic origin. Improved methods or novel therapies are urgently needed to eliminate the development of metastases. Artesunate is a semi-synthetic derivative of artemisinin used for trarment of malaria and cancer. The purpose of this study was to investigate the anti-cancer effect of artesunate and the role on STAT3 signaling in A375 human melanoma cell line. METHODS: Melanoma cells were treated with artesunate at concentrations of 0-5 µM for 24 and 48 h. The inhibition of cell viability, colony formation, migration, invasion, adhesion, percentage of apoptotic cells, and expressions of signal transducer and activator of transcription-3 (STAT3) and related proteins were examined. RESULTS: Artesunate inhibited cellular proliferation of cancer cells by induction of apoptosis at sub-toxic doses. Cells treated with artesunate showed an inhibition in adhesion to extracellular matrix substrate matrigel and type IV collagen. Artesunate treatment showed a decreased cellular migration, invasion, and colony formation in melanoma cells. Artesunate also inhibited STAT3 and Src activations and STAT3 related protein expressions; such as metalloproteinase 2 (MMP-2), MMP-9, Mcl-1, Bxl-xL, vascular endothelial growth factor (VEGF), and Twist. Moreover, overexpression of constitutively active STAT3 in A375 cells attenuated the anti-proliferative, apoptotic and anti-invasive effects of artesunate. CONCLUSION: The results obtained from this study demonstrated that the anticancer activity of artesunate occurred via STAT3 pathway and its target proteins. Therefore, it can be suggested that artesunate may be an important candidate molecule in the treatment of melanoma.