Apoptosis, a programmed cell death process preventing cancer development, can be evaded by cancer cells. AMP-activated protein kinase (AMPK) regulates energy levels and is a key research topic in cancer prevention and treatment. Some bioactive components of Hibiscus sabdariffa L. (HAs), including anthocyanins, have potential anticancer properties. Our study investigated the in vitro cytotoxic potential and mode of action of HAs extracts containing anthocyanins in colorectal cancer cells. The results showed that Hibiscus anthocyanin-rich extracts induced apoptosis in human colorectal cancer cells through the activation of multiple signaling pathways of AMPK. We observed the dose–response and time-dependent induction of apoptosis with HAs. Subsequently, the activation of Fas-mediated proteins triggered apoptotic pathways associated with Fas-mediated apoptosis-related proteins, including caspase-8/tBid. This caused the release of cytochrome C from the mitochondria, resulting in caspase-3 cleavage and apoptosis activation in intestinal cancer cells. These data elucidate the relationship between Has’ regulation of apoptosis-related proteins in colorectal cancer cells and apoptotic pathways.

Age at onset is one of the most important clinical features of schizophrenia that could indicate greater genetic loadings. Neurological soft signs (NSS) are considered as a potential endophenotype for schizophrenia. However, the association between NSS and different age-onset schizophrenia still remains unclear. We aimed to compare risk model in patients with early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) with NSS. This study included 262 schizophrenia patients, 177 unaffected first-degree relatives and 243 healthy controls. We estimated the discriminant abilities of NSS models for early-onset schizophrenia (onset age < 20) and adult-onset schizophrenia (onset age ≥ 20) using three data mining methods: artificial neural networks (ANN), decision trees (DT) and logistic regression (LR). We then assessed the magnitude of NSS performance in EOS and AOS families. For the four NSS subscales, the NSS performance were greater in EOS and AOS families compared with healthy individuals. More interestingly, there were significant differences found between patients’ families and control group in the four subscales of NSS. These findings support the potential for neurodevelopmental markers to be used as schizophrenia vulnerability indicators. The NSS models had higher discriminant abilities for EOS than for AOS. NSS were more accurate in distinguishing EOS patients from healthy controls compared to AOS patients. Our results support the neurodevelopmental hypothesis that EOS has poorer performance of NSS than AOS. Hence, poorer NSS performance may be imply trait-related NSS feature in EOS.

Diabetes mellitus (DM) significantly increases global morbidity and mortality through cardiovascular complications, particularly atherosclerosis, characterized by chronic inflammation, oxidative stress, and endothelial dysfunction.

Diabetic cardiomyopathy (DCM) under glucolipotoxic stress is sustained by a reactive oxygen species (ROS)-driven circuit in which oxidative DNA damage and nitrosative injury prime NLR family pyrin domain containing 3 (NLRP3) inflammasome assembly, triggering caspase-1 activation, gasdermin D (GSDMD) cleavage, and pyroptotic cardiomyocyte death that propagates apoptosis and fibrotic remodeling. Whether melatonin can disrupt this oxidative-pyroptotic axis when both hyperglycemia and dyslipidemia coexist, the metabolic context most refractory to current therapy has not been established. Apolipoprotein E-deficient (ApoE⁻/⁻) mice were subjected to streptozotocin-induced hyperglycemia and high-fat diet-induced dyslipidemia, then treated with oral melatonin (20 mg/kg/day) for 8 weeks. Despite unchanged fasting glycemia, melatonin attenuated cardiac oxidative stress, reducing 8-OHdG and inducible nitric oxide synthase while restoring Nrf2. Suppression of nuclear factor-κB and NLRP3 was accompanied by lowered interleukin-1β, caspase-1, and GSDMD, indicating disrupted inflammasome priming and pyroptotic execution. Downstream pathology was concurrently attenuated, with reduced TUNEL-positive cardiomyocytes, normalized Bax/Bcl-2 ratio, lower natriuretic peptide expression, diminished interstitial fibrosis, and improved electrocardiographic parameters. These findings position melatonin as a cardioprotective agent that operates despite persistent fasting hyperglycemia, acting through combined attenuation of lipid burden, cumulative glycemic stress, oxidative stress, and inflammatory signaling to arrest downstream apoptotic and fibrotic remodeling under glucolipotoxic conditions, providing a mechanistic rationale for adjunctive melatonin therapy in DCM.

Cardio-renal metabolic (CRM) syndrome, characterized by insulin resistance and dyslipidemia, disrupts renal insulin signaling, enhances oxidative stress, and activates inflammasome pathways, ultimately promoting renal fibrosis and kidney dysfunction. Aberrant renal gluconeogenesis has emerged as a critical contributor to tubular injury under cardiometabolic stress; however, its mechanistic linkage to inflammatory and fibrotic remodeling remains incompletely defined. In this study, ApoE^−/− mice subjected to streptozotocin administration and a high-fat diet developed pronounced cardiometabolic dysfunction, accompanied by elevated blood urea nitrogen, creatinine, uric acid, and glycated hemoglobin levels, as well as severe renal histopathological alterations. N-Acetylcysteine (NAC) supplementation significantly improved metabolic abnormalities and attenuated tubular dilation, glomerular hypertrophy, and mesangial expansion. Mechanistically, NAC suppressed renal gluconeogenesis by downregulating glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression and mitigated epithelial–mesenchymal transition by restoring E-cadherin and reducing vimentin expression, thereby limiting fibrotic remodeling. Consistent with in vivo findings, NAC reduced reactive oxygen species production, restored PI3K/Akt-dependent insulin signaling, and inhibited inflammasome activation in NRK-52E renal tubular cells exposed to high glucose and oleic acid, resulting in attenuation of inflammatory signaling and gluconeogenic activity. Collectively, these results demonstrate that NAC mitigates cardiometabolic stress-induced renal injury by modulating inflammasome activation and gluconeogenic reprogramming, highlighting its potential as a mechanistic modulator of renal fibrosis under CRM conditions.

Diabetes mellitus is frequently associated with cognitive dysfunction, primarily attributed to impaired hippocampal neurogenesis, oxidative stress, inflammation, and pyroptosis. Caffeic acid (CA), a dietary polyphenol, has demonstrated antioxidant and neuroprotective effects. This study evaluated the protective role of CA under diabetic-like conditions using an in vitro glucolipotoxicity model in HT-22 hippocampal neurons exposed to high glucose and oleic acid (HG + OA). CA was administered at low (5 µM) and high (25 µM) concentrations prior to HG + OA treatment. CA significantly enhanced neuronal viability and restored the expression of neurogenesis markers (Nestin, DCX, NeuN) and synaptic proteins (PSD-95, Synaptophysin). Furthermore, CA elevated antioxidant enzyme levels (Nrf2, catalase, SOD-1), regulated apoptosis through increased Bcl-2 and decreased BAX expression, and attenuated inflammatory responses. Pyroptosis was also suppressed, as evidenced by reduced gasdermin D (GSDMD) expression. These findings suggest that CA confers multifactorial neuroprotection against glucolipotoxic injury, and may serve as a dietary modulator for mitigating diabetes-associated cognitive decline in vitro.