GuanXinNing Tablet Attenuates Alzheimer's Disease via Improving Gut Microbiota, Host Metabolites, and Neuronal Apoptosis in Rabbits.

Based on accumulating evidence, Alzheimer's disease (AD) is related to hypercholesterolemia, gut microbiota, and host metabolites. GuanXinNing Tablet (GXN) is an oral compound preparation composed of two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., both of which exert neuroprotective effects. Nevertheless, the effect of GXN on AD is unknown. In the present study, we investigated whether GXN alters cholesterol, amyloid-beta (Aß), gut microbiota, serum metabolites, oxidative stress, neuronal metabolism activities, and apoptosis in an AD model rabbit fed a 2% cholesterol diet. Our results suggested that the GXN treatment significantly reduced cholesterol levels and Aß deposition and improved memory and behaviors in AD rabbits. The 16S rRNA analysis showed that GXN ameliorated the changes in the gut microbiota, decreased the Firmicutes/Bacteroidetes ratio, and improved the abundances of Akkermansia and dgA-11_gut_group. 1H-NMR metabolomics found that GXN regulated 12 different serum metabolites, such as low-density lipoprotein (LDL), trimethylamine N-oxide (TMAO), and glutamate (Glu). In addition, the 1H-MRS examination showed that GXN remarkably increased N-acetyl aspartate (NAA) and Glu levels while reducing myo-inositol (mI) and choline (Cho) levels in AD rabbits, consequently enhancing neuronal metabolism activities. Furthermore, GXN significantly inhibited oxidative stress and neuronal apoptosis. Taken together, these results indicate that GXN attenuates AD via improving gut microbiota, host metabolites, and neuronal apoptosis.

Masticatory properties in pre-modern Holocene populations from Northern China.

Recent studies indicate that evolution of the craniofacial skeleton is influenced by dietary behavior, which in turn alters masticatory efficacy and temporomandibular joint (TMJ) stability. In this study the mechanical properties of the masticatory system and the integrity of the TMJ in human populations from Northern China, dated to between 3800 BCE and 100 CE, were assessed. The results demonstrate that the mechanical efficiency is comparable to other modern human populations, though variations are present across different populations. While the ratio of overall weighted muscle efficiency for incisor loading vs. molar loading in pastoral and some recent agricultural groups is similar to early Homo sapiens, the ratio in more ancient agricultural groups is similar to the ratio in populations with heavy anterior paramasticatory activities, such as Neandertals, Inuits, and Native Americans. The TMJ vulnerability negatively correlates with the maxillary dental arch size, and positively with the condylar size. These findings suggest that there are multi-directional strategies in adaptation to heavy anterior teeth loading, such as increasing anterior teeth loading efficiency, increasing facial height, increasing facial breath and facial orthognathy, or decreasing anterior facial length. Furthermore, populations or individuals with a smaller dental arch and high biting efficiency could more easily injure the TMJ during unilateral loadings, which may explain the higher prevalence of TMJ disorders in modern humans, especially in women. These findings further reflect the impact of diachronic changes of the masticatory apparatus and lifestyle and their impact on oral health during recent human history.

Effects of selenium and silicon on enhancing antioxidative capacity in ramie (Boehmeria nivea (L.) Gaud.) under cadmium stress.

Hydroponic experiments were performed to investigate the ameliorating effects and mitigation mechanisms of selenium and silicon on Cd toxicity in Boehmeria nivea (L.) Gaud. Metal accumulation, chlorophyll content, activities of antioxidant enzymes, and antioxidant contents in ramie were evaluated. The results revealed that cadmium was mainly accumulated in the roots of plants rather than in the aerial parts. Additionally, under 5 mg L(-1) Cd stress, both Se (1 µmol L(-1)) and Si (1 mmol L(-1)) treatments decreased the Cd concentrations in plants. Besides, the treatments also inhibited the translocation ability of Cd from roots to the aboveground parts, which might be related to the decline of generation of reactive oxygen species (ROS). The application of Se and/or Si ameliorated Cd toxicity via stimulating the activities of antioxidant enzymes such as superoxide dismutase (SOD), guaiacol peroxidase (POD), and ascorbate peroxidase (APX), which resulted in the significant decrease of the contents of malondialdialdehyde (MDA) and hydrogen peroxide (H2O2) in ramie leaves. In addition, the content of nonenzymatic antioxidant such as glutathione (GSH) was increased significantly through the addition of selenite and silicate. Also, ascorbate (AsA) and vitamin E played a crucial role in scavenging excess ROS within plants. On the whole, appropriate doses of Se and Si were found to benefit plant growth and enhance the ability of ramie to alleviate Cd-induced stress. Moerover, the effects of combination of Se and Si appeared to be more superior compared to addition separately in response to Cd stress.

Combined anti-tumor effects of IFN-α and sorafenib on hepatocellular carcinoma in vitro and in vivo.

Hepatocellular carcinoma (HCC) is among the most common and aggressive cancers worldwide, and novel therapeutic strategies are urgently required to improve clinical outcome. Interferon-alpha (IFN-α) and sorafenib are widely used as anti-tumor agents against various malignancies. In this study, we investigated the combined effects of IFN-α and sorafenib against HCC. We demonstrated that the combination therapy synergistically suppressed HCC cellular viability, arrested cell cycle propagation and induced apoptosis in HCC cells. Further research revealed that IFN-α and sorafenib collaboratively regulated the expression levels of cell cycle-related proteins Cyclin A and Cyclin B as well as the pro-survival Bcl-2 family proteins Mcl-1, Bcl-2 and Bcl-X(L). Moreover, sorafenib inhibited IFN-α induced oncogenic signaling of STAT3, AKT and ERK but not the activation of the tumor suppressor STAT1. Xenograft experiments also confirmed the combined effects of IFN-α and sorafenib on tumor growth inhibition and apoptosis induction in vivo. In conclusion, these results provide rationale for the clinical application of IFN-α and sorafenib combination therapy in HCC treatment.

[Water mobility of diffusion MRI in prediction of response to chemoembolization in liver cancer].

OBJECTIVE: To investigate the value of pretreatment and posttreatment changes of apparent diffusion coefficients (ADCs) in predicting response to chemoembolization in liver cancer. METHODS: Patients with liver cancer were examined with diffusion-weighted MRI at two b values (0 and 500 s/mm(2)) before and after chemoemblization. Quantitative ADC maps were calculated using images under b values of 0 and 500 s/mm(2). The mean ADC values of lesions before and after chemoemblization were compared. The correlation of response to chemoembolization with ADC value was analyzed. RESULTS: The mean value of pretreatment ADC in non-responding lesions were significantly higher than that in the responding lesions (1.687 x 10(-3) mm(2)/s vs. 1.278 x 10(-3) mm(2)/s, P < 0.05). The results of receiver operator characteristic (ROC) analysis showed that when a threshold ADC value was set on 1.618 x 10(-3) mm(2)/s, the sensitivity and specificity for identification of non-responding lesions were 96.0% and 77.8%, respectively. After transarterial chemoembolization, the responding lesions had a significant increase in ADC values than non-responding lesions (32.6% vs. 5.2%, P = 0.025). The results of ROC analysis indicated that when the changes of ADC value for identification of responding lesions before and after transarterial chemoembolization was > or = 16.2%, the sensitivity and specificity were 72% and 100%, respectively. However, no significant change was observed in normal liver parenchyma and spleen (P > 0.05). CONCLUSION: Pretreatment mean ADC value can be used to predict the response to chemoembolization, and for selection of therapy in liver cancer. A significant increase in mean ADC can be observed if the lesions responds to chemoembolization.