Improving the Effects of Mulberry Leaves and Neochlorogenic Acid on Glucotoxicity-Induced Hepatic Steatosis in High Fat Diet Treated db/db Mice.

There are many complications of type 2 diabetes mellitus. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two complications related to the increased lipid accumulation in the liver. Previous studies have shown that mulberry leaf water extract (MLE) has the effect of lowering lipid levels in peripheral blood, inhibiting the expression of fatty acid synthase (FASN) and increasing the activity of liver antioxidant enzymes superoxide dismutase (SOD) and catalase. Our study aimed to investigate the role of MLE and its main component, neochlorogenic acid (nCGA), in reducing serum lipid profiles, decreasing lipid deposition in the liver, and improving steatohepatitis levels. We evaluated the antioxidant activity including glutathione (GSH), glutathione reductase (GRd), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD), and catalase was tested in mice fed with MLE and nCGA. The results showed a serum lipid profile, and fatty liver scores were significantly increased in the HFD group compared to the db/m and db mice groups, while liver antioxidant activity significantly decreased in the HFD group. When fed with HFD + MLE or nCGA, there was a significant improvement in serum lipid profiles, liver fatty deposition conditions, steatohepatitis levels, and liver antioxidant activity compared to the HFD group. Although MLE and nCGA do not directly affect the blood sugar level of db/db mice, they do regulate abnormalities in lipid metabolism. These results demonstrate the potential of MLE/nCGA as a treatment against glucotoxicity-induced diabetic fatty liver disease in animal models.

Hibiscus Anthocyanins Extracts Induce Apoptosis by Activating AMP-Activated Protein Kinase in Human Colorectal Cancer Cells.

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.

Mulberry leaf extract and neochlorogenic acid ameliorate glucolipotoxicity-induced diabetic nephropathy in high-fat diet-fed db/db mice.

Diabetic nephropathy, a major diabetes complication, is often exacerbated by glucolipotoxicity. The potential benefits of mulberry leaf extract (MLE) and its primary component, neochlorogenic acid (nCGA), in combating this condition have not been extensively explored. High-fat diet-fed db/db mice were employed as a model for glucolipotoxicity-induced diabetic nephropathy. The mice were treated with MLE or nCGA, and their body weight, insulin sensitivity, blood lipid profiles, and kidney function were assessed. In addition, modulation of the JAK-STAT, pAKT, Ras, and NF-κB signaling pathways by MLE and nCGA was evaluated. MLE and nCGA did not significantly decrease blood glucose level but effectively mitigated the adverse effects of a high-fat diet on blood lipid profile and kidney function. Improvements in body weight, insulin sensitivity, and kidney structure, along with a reduction in fibrosis, were observed. Both MLE and nCGA regulated lipid metabolism abnormalities, significantly inhibited the accumulation of glycosylated substances in glomeruli, and modulated crucial signaling pathways involved in diabetic nephropathy. Although they do not directly affect blood glucose level, MLE and nCGA show significant potential in managing glucolipotoxicity-induced diabetic nephropathy by targeting lipid metabolism and key molecular pathways. The present findings suggest MLE and nCGA may be promising therapeutic agents for diabetic nephropathy, and further exploration in human patients is warranted.

Risk Model Assessment in Early-Onset and Adult-Onset Schizophrenia Using Neurological Soft Signs.

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.

Minor physical anomalies in adolescents at risk for substance use and early sex.

Minor physical anomalies (MPAs) are associated with disruptions of fetal development. We propose that the same genetic compositions that contribute to the presence of MPAs, also predispose individuals to health-compromising behaviors, thus considering MPAs as particular endophenotypes.We developed a screening questionnaire for problematic conduct, substance abuse, and early sexual practice. A total of 108 adolescents (55 males, 50.9%) aged 11 to 19 years were recruited and further divided into case and control groups according to their answers to the questions of health behaviors mentioned above. We then measured their MPAs that included qualitative and quantitative physical features. Stepwise logistic regression and the receiver operating characteristic (ROC) analyses were used to determine the predictive values of MPAs for behavioral outcomes.The obliquity of palpebral fissure and the head MPAs were negatively associated with substance use. In the ROC analysis, the model provided an area under curve (AUC) of 0.91 with prediction indices being 0.89 for sensitivity and 0.85 for specificity. In addition, the feet MPAs and outer canthal distance were positively, whereas the obliquity of palpebral fissure and ear rotation was negatively associated with early sexual practices. The AUC for early sexual practice was 0.91 and the prediction indexes were 0.87 for sensitivity and 0.88 for specificity.Certain MPAs were associated with adolescent substance use and early sex, which suggests a neurodevelopmental etiology for behavioral outcomes.

Sleep apnea is associated with an increased risk of mood disorders: a population-based cohort study.

PURPOSE: The symptoms of sleep apnea, such as sleep fragmentation and oxygen desaturation, might be risk factors for subsequent mood disorder (MD), but associations between sleep apnea and MD remain unclear. This nationwide population-based study thus aimed to identify the risk of MD in patients with vs. without sleep apnea. METHODS: This cohort study used data from the National Health Insurance database. In total, 5415 patients diagnosed with sleep apnea between 2000 and 2010 were evaluated, and 27,075 matched non-sleep apnea enrollees were included as a comparison cohort. All subjects were followed until 2011. The Cox proportional hazard ratio (HR) was used to investigate the relationship between MD and sleep apnea while controlling covariates and comorbidities of sleep apnea. RESULTS: Of 5415, 154 patients with sleep apnea (2.84 %) were diagnosed with MD during the follow-up period in comparison with 306 of 27,075 individuals (1.13 %) without antecedent sleep apnea. After adjusting for the selected factors and comorbidities, we found that patients with sleep apnea were from 1.82- to 2.07-fold greater risk of MD than the comparisons. Of the three subcategories of MD (major depressive disorder, bipolar disorder, and unspecified MD), sleep apnea had the highest predisposing risk with respect to major depressive disorder (adjusted HR from 1.82 to 2.07) and bipolar disorder (adjusted HR from 2.15 to 3.24). CONCLUSIONS: There is a greater likelihood of MD manifesting in patients with a history of sleep apnea. Health professionals are thus advised to carefully monitor the psychological impacts of sleep apnea.

Improving risk assessment and familial aggregation of age at onset in schizophrenia using minor physical anomalies and craniofacial measures.

Age at onset is the most important feature of schizophrenia that could indicate its origin. Minor physical anomalies (MPAs) characterize potential marker indices of disturbances in early neurodevelopment. However, the association between MPAs and age at onset of schizophrenia is still unclear. We aimed to compare risk assessment and familial aggregation in patients with early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) with MPAs and craniofacial measures.We estimated the risk assessment of MPAs among patients with EOS (n = 68), patients with AOS (n = 183), nonpsychotic relatives (n = 147), and healthy controls (n = 241) using 3 data-mining algorithms. In addition, we assessed the magnitude of familial aggregation of MPAs with respect to the age at onset of schizophrenia.The performance of EOS was superior to that of AOS, with discrimination accuracies of 89% and 76%, respectively. Combined MPA scores as the risk assessment were significantly higher in all schizophrenia subgroups and the nonpsychotic relatives of EOS patients than in the healthy controls. The recurrence risk ratio for familial aggregation of the MPA scores of EOS families (odds ratio 9.27) was substantially higher than that of AOS families (odds ratio 2.47).The results highlight that EOS improves risk assessment and has a severe magnitude of familial aggregation of MPAs. These findings indicate that EOS might result from a stronger genetic susceptibility to neurodevelopmental deficits.