Elucidation of the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus on rats fed a western-style diet via a multi-omics approach.

Long-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MSE technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD.

Exploration of the structural mechanism of hydrogen (H2)-promoted horseradish peroxidase (HRP) activity via multiple spectroscopic and molecular dynamics simulation techniques.

Horseradish peroxidase (HRP) is an enzyme that is widely used in various fields. In this study, the effects of molecular hydrogen (H2) on the activity and structural characteristics of HRP were investigated by employing multiple spectroscopic techniques, atomic force microscopy (AFM) and molecular dynamics (MD) simulations. The results demonstrated that H2 could enhance HRP activity, especially in 1.5 mg/L hydrogen-rich water (HRW). The structural analysis results showed that H2 might alter HRP activity by affecting the active sites, secondary structure, hydrogen bonding network, CS groups, and morphological characteristics. The MD results also confirmed that H2 could increase the FeN bond distance in the active site, affect the secondary structure, and increase the number of hydrogen bonds. The MD results further suggested that H2 could increase the number of salt bridges, and lengthen the SS bonds in HRP. This study primarily revealed the mechanism by which H2 enhances the HRP activity, providing insight into the interactions between gas and macromolecular proteins. However, some of the results obtained via MD simulations still need to be verified experimentally. In addition, our study also provided a new convenient strategy to enhance enzyme activity.

Study on the role of histone epigenetic modification in replication of hepatitis B virus.

Hepatitis B virus (HBV) infection is a global health problem and lacks effective therapies in clinic. This study attempted to investigate the role of histone deacetylase 3 (HDAC3) in HBV replication. Cells were treated with 1.3 folds of HBV genome. The expression patterns of HDAC3, miR-29a-3p, and nuclear factor of activated T-cells 5 (NFAT5) in cells were determined by real-time quantitative polymerase chain reaction and Western blot analysis. HBV replication was assessed by measurements of HBV DNA, HBV RNA, hepatitis B surface antigen, and hepatitis B E antigen. After chromatin immunoprecipitation and RNA pull-down assays to testify gene interactions, rescue experiments and animal experiments were performed to assess the role of miR-29a-3p/NFAT5 in HBV replication and the role of HDAC3 in vivo. HDAC3 level was decreased by pHBV1.3 plasmid in a concentration-dependent manner. HDAC3 overexpression can inhibit HBV replication, which was neutralized by miR-29a-3p overexpression or NFAT5 downregulation. Mechanically, HDAC3 overexpression reduced the enrichment of histone 3 lysine 9 acetylation on the miR-29a-3p promoter to inhibit miR-29a-3p expression and then promote NFAT5 transcription. In vivo, HDAC3 restrained HBV replication through the miR-29a-3p/NFAT5 axis. Overall, HDAC3 downregulation was associated with HBV replication and HDAC3 overexpression inhibited HBV replication through H3K9ac/miR-29a-3p/NFAT5.

Efficacy and Risk Factors of Pyrrotinib in Second- and Third-Line Treatments for HER2-Positive Advanced Breast Cancer.

A study to examine the efficacy and risk factors associated with pyrrotinib in the second- and third-line treatment of advanced breast cancer with Human epidermal growth factor receptor 2- (HER2-) positive cells was conducted. Progression-free survival (PFS) was assessed as the primary endpoint, and the objective response rate (ORR), overall survival (OS), and safety were secondary endpoints. Across all the patients, the ORR was 48.57%, and the disease control rate (DCR) was 94.29%. In the follow-up period, the median PFS was 15 months, and second-line treatment had significantly longer PFS than third-line treatment (P = 0.027). The OS among all the patients was up to 28 months, but the median OS has not yet been reached. Diarrhea (69.57%) was the most important AE, mainly in grades 1 and 2. According to the COX regression analysis, brain metastasis was a risk factor for PFS, while second-line treatment and capecitabine chemotherapy were relevant to a longer PFS correlation among patients. In the second- and third-line treatment, pyrrotinib is still highly effective and safe. Pyrrotinib is a potential ideal salvage treatment plan for patients who failed in first-line treatments.

Nostoc sphaeroids Kütz ameliorates hyperlipidemia and maintains the intestinal barrier and gut microbiota composition of high-fat diet mice.

Hyperlipidemia is associated with chronic inflammation and intestinal dysbiosis. The purpose of this study was to investigate the protective effect of Nostoc sphaeroids Kütz (NO) on diet-induced hyperlipidemia in mice. Experimental animals received a high-fat diet (HFD) for 4 weeks, then an HFD supplemented with 2.5% or 7.5% NO for 6 weeks. HFD-fed mice exhibited a significant increase in serum total cholesterol, triglycerides, and low-density lipid cholesterol, and a decrease in high-density lipid cholesterol. NO supplementation was associated with significantly lower dyslipidemia, decreased intestinal inflammation, and inhibition of toll-like receptor 4 gene repression in HFD-fed mice. Results suggest that NO treatment protected the integrity of the intestinal barrier. NO treatment was also associated with significant changes in the intestinal microbiota induced by HFD and an increase in the Firmicutes-to-Bacteroidetes ratio. Furthermore, NO treatment was also inversely correlated with mice obesity and hyperlipidemia NO and was associated with no significant in fecal short-chain fatty acids. In conclusion, NO significantly ameliorated hyperlipidemia induced by a HFD in mice, potentially via a decrease intestinal inflammation, increase in intestinal barrier integrity, and amelioration in the gut microbiota.

Toxicity Assessment of Chinese Herbal Medicine Cynomorium songaricum Rupr.

Cynomorium songaricum Rupr, known as Suo Yang, is most commonly used to treat fatigue, protect the liver, and invigorate kidneys in Northwest China. Given the wide medicinal utilisation and lack of safety evaluation, this work evaluated the acute toxicity, genetic toxicity, and 90-day repeated oral toxicity of Suo Yang. Twenty Kunming mice were orally given Suo Yang once and observed for 14 days in the acute toxicity test. The genetic toxicity of Suo Yang was tested using in vivo and vitro assays (bacterial reverse mutation test, mouse bone marrow micronucleus assay, and spermatocyte chromosomal aberration assay). In the 90-day repeated oral toxicity study, 80 SD rats were randomly divided into 4 groups and then orally given Suo Yang at different concentrations (1.04, 2.08 or 4.16 g/kg), while the control group was given sterile water. In the acute toxicity test, no abnormal behaviour or mortality was found in mice. The results suggest that the maximum tolerable dose of Suo Yang is greater than 15 g/kg. In the genotoxicity studies, no revertant colonies were produced in vitro. In the in vivo assays, no increased frequencies of micronuclei or structural abnormalities of spermatocyte chromosomes were found. In the 90-day repeated oral toxicity study, no significant toxicological manifestations were observed in haematological parameters or clinical and pathological examinations. In summary, these results suggest that Suo Yang at the given doses does not cause adverse effects in animals. Thus, Suo Yang can reasonably be considered a safe herbal medicine.

Nostoc sphaeroids Kütz powder ameliorates diet-induced hyperlipidemia in C57BL/6j mice.

BACKGROUND: Hypercholesterolemia is a disease associated with numerous health problems. Growing evidence indicates that hypercholesterolemia, hyperlipidemia is closely linked to chronic inflammation, which can lead to cardiovascular disease, fatty liver disease, and type 2 diabetes. OBJECTIVE: The purpose of this study was to investigate the protective effect of Nostoc sphaeroids Kütz (NO) on diet-induced hyperlipidemia in mice. DESIGN: At first, experimental animals received a high-fat diet (HFD) for 4 weeks, and then received a HFD supplemented with 2.5% or 7.5% NO for 6 weeks. In the current study, results show that treatment with NO decreases weight gain and liver index induced by HFD. In addition, the serum levels of TC, TG and LDL are significantly decreased in NO treatment groups. RESULTS: From the results of Oil Red staining and Hematoxylin and eosin staining (HE), treatment with NO significantly reduces liver lipid accumulation and protect liver structure. Further analysis reveals that NO has positive effects on liver lipid metabolism and inflammation, as showed by the lower protein expressions of FAS and SREBP-1, the lower concentrations of TNF-α, IL-1ß, IL-6, and the lower gene expressions of TNF-α, IL-1ß, IL-6 and NF-kB. CONCLUSIONS: Our results indicate that NO may significantly ameliorate diet-induced hyperlipidemia, which is possibly associated with improving liver lipid metabolism and reducing chronic inflammation.

The Research of Improved Grey GM (1, 1) Model to Predict the Postprandial Glucose in Type 2 Diabetes.

Diabetes may result in some complications and increase the risk of many serious health problems. The purpose of clinical treatment is to carefully manage the blood glucose concentration. If the blood glucose concentration is predicted, treatments can be taken in advance to reduce the harm to patients. For this purpose, an improved grey GM (1, 1) model is applied to predict blood glucose with a small amount of data, and especially in terms of improved smoothness it can get higher prediction accuracy. The original data of blood glucose of type 2 diabetes is acquired by CGMS. Then the prediction model is established. Finally, 50 cases of blood glucose from the Henan Province People's Hospital are predicted in 5, 10, 15, 20, 25, and 30 minutes, respectively, in advance to verify the prediction model. The prediction result of blood glucose is evaluated by the EGA, MSE, and MAE. Particularly, the prediction results of postprandial blood glucose are presented and analyzed. The result shows that the improved grey GM (1, 1) model has excellent performance in postprandial blood glucose prediction.