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Breast cancer remains a significant challenge in oncology, necessitating the exploration of novel therapeutic options. This study investigates the anticancer effects of ethanol and n-hexane fractions derived from the methanol extract of the Leptastrea purpurea sponge on T47D breast cancer cells. Employing cytotoxicity assays (MTT and WST-1), mitochondrial transmembrane potential assays, and protein expression analysis of p53, Caspase-3, and Bax, we aimed to elucidate the mechanisms underlying their potential anticancer activity. LC-MS/MS analysis was utilized to identify active compounds within the fractions. The results of the experiment demonstrate that the ethanol fraction exhibits significant efficacy against T47D breast cancer cells, with an IC50 value of 25.36 μg/mL indicating potent cytotoxicity. At a concentration of 1508 μg/mL, it induces cell death in 95% of T47D cells, highlighting its specificity in targeting breast cancer cells. Comparative analysis with cisplatin reveals a 9.92% higher rate of cell death induced by the ethanol fraction, suggesting superior apoptosis induction capability. Flow cytometry results show increased p53 expression at concentrations of 754 and 1508 μg/mL, with a concentration-dependent pattern. Furthermore, notable increases in Bax protein expression at concentrations of 377 and 754 μg/mL suggest the involvement of the ethanol fraction in regulating apoptosis. In conclusion, the ethanol fraction demonstrates promising potential as a cytotoxic and apoptosis-inducing agent for breast cancer therapy. These findings underscore the importance of exploring natural products from marine sources as potential anticancer agents. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a complex heterogeneous condition that affects women of reproductive age, conferring increased cardiovascular morbidity and mortality. The syndrome is characterized by oligomenorrhea, hyperandrogenism, and/or polycystic ovaries and is often associated with obesity and type 2 diabetes. Individuals are predisposed to PCOS by environmental factors and risk variants in genes mostly involved in ovarian steroidogenesis and/or insulin resistance. Genetic risk factors have been identified by both familial and genome-wide (GW) association studies. However, most genetic components are still unknown and missing heritability needs to be elucidated. To learn more about the genetic determinants of PCOS, we performed a GW study in genetically highly homogeneous peninsular families. PATIENTS AND METHODS: We conducted the first GW-linkage and linkage disequilibrium (i.e., linkage + association) study in Italian families with PCOS. RESULTS: We identified several novel risk variants, genes, and pathways potentially implicated in the pathogenesis of PCOS. Specifically, we detected 79 novel variants with significant GW-linkage and/or -association with PCOS across 4 inheritance models (p < 0.00005), of which 50 variants were within 45 novel PCOS-risk genes. CONCLUSIONS: This is the first GW-linkage and linkage disequilibrium study performed in peninsular Italian families and reporting novel genes in PCOS. [ABSTRACT FROM AUTHOR]

Key factors of pyroptosis play an important role in the inflammatory response to connective tissue disease (CTD). However, information on active and stable stages of CTD is scarce. To distinguish the differences of concentrations of C-reactive protein (CRP), caspase 1, caspase 4, caspase 5 and sCD14 in plasma between the patients with active and stable stages of CTD. A cohort study was conducted to recruit patients diagnosed with CTD of active phase and stable phase as well as health control. These data included the analysis of the concentration of sCD14, caspase 1, caspase 4 and caspase 5 in peripheral plasma by ELISA. The Wilcoxon rank-sum test was used to compare the two groups. The sex ratio and ages of the three groups were not different statistically. The concentrations of sCD14, caspase4 and caspase5 of plasma in the CTD of active phase and the stable phase as well as the health control. The concentration of caspase 1 in active phase of CTD (470.19 [422.33–513.14] pmol/L) was significantly higher than that in stable group (203.95 [160.94–236.12] pmol/L) and healthy control (201.65 [191.11–240.35] pmol/L] pmol/L) (p

Abstract: A previous data showed that the hypoxia mimetic compound CoCl2 induced cleavage of HuR and subsequent apoptosis in human oral cancer cells. We also previously demonstrated that exposure of NT-2 human neuronal precursor cells to hypoxia resulted in changes in sphingolipid levels and apoptosis. Since it is known that CoCl2 induces cleavage of HuR, we investigated whether there is a link between HuR cleavage and the observed sphingolipid changes in cells exposed to hypoxia, and whether this link is associated with the induction of apoptosis. Exposure of hepatocytes to direct hypoxia by means of a hypoxic chamber resulted in acid sphingomyelinase activation and ceramide elevation. The elevation in ceramide levels was associated with activation of caspase 5 and the subsequent cleavage of HuR and apoptotic cell death. These data raise the possibility that acid sphingomyelinase and caspase 5 are each potential targets for treating hypoxia (ischemia)-induced liver injury. [Copyright &y& Elsevier]