Intermittent hypoxia is involved in gut microbial dysbiosis in type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea (OSA)-hypopnea syndrome (OSAHS) has been recognized as a comorbidity of type 2 diabetes mellitus (T2DM); more than half of T2DM patients suffer from OSAHS. Intermittent hypoxia (IH) plays an important role in metabolic diseases, such as obesity and OSAHS, through various mechanisms, including altering the gut microecological composition and function. Therefore, it is important to study the role of gut microbiota in T2DM patients with OSAHS, which has a high incidence and is prone to several complications. AIM: To assess whether IH is involved in altering the fecal microbiome in T2DM patients with OSAHS. METHODS: Seventy-eight participants were enrolled from Henan Province People's Hospital and divided into healthy control (HC, n = 26), T2DM (n = 25), and T2DM + OSA (n = 27) groups based on their conditions. The fecal bacterial DNA of the research participants was extracted and subjected to 16S ribosomal RNA sequencing. The clinical indices, such as insulin resistance index, homocysteine (HCY) concentration, and the concentrations of inflammatory factors in the peripheral blood, were assessed and recorded. RESULTS: Group T2DM + OSA had the highest apnea-hypopnea index (AHI) (2.3 vs 3.7 vs 13.7), oxygen desaturation index (0.65 vs 2.2 vs 9.1), HCY concentration (9.6 µmol/L vs 10.3 µmol/L vs 13.81 µmol/L) and C-reactive protein (CRP) concentrations (0.3 mg/L vs 1.43 mg/L vs 2.11 mg/L), and lowest mean oxygen saturation (97.05% vs 96.6% vs 94.7%) among the three groups. Twelve and fifteen key differences in amplicon sequence variants were identified when comparing group T2DM + OSA with groups T2DM and HC, respectively. We found progressively decreased levels of Faecalibacterium, Eubacterium, and Lachnospiraceae, and an increase in the level of Actinomyces, which strongly correlated with the HCY, CRP, fasting plasma glucose, and hemoglobin A1c concentrations, AHI, mean oxygen saturation, and insulin resistance index in group T2DM + OSA (P < 0.05). CONCLUSION: For T2DM patients with OSAHS, IH may be involved in selective alterations of the gut microbiota, which may affect the pathophysiological development of T2DM and DM-related complications.

Therapeutic effects of herbal formula Huangqisan on metabolic disorders via SREBF1, SCD1 and AMPK signaling pathway.

OBJECTIVE: Metabolic syndrome is a complex medical condition that has become an alarming epidemic, but an effective therapy for this disease is still lacking. The use of the herbal formula Huangqisan (HQS) to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.; however, its therapeutic effects and underlying mechanisms remain elusive. METHODS: To investigate the beneficial effects of HQS on metabolic disorders, high-fat diet-induced obesity (DIO), leptin receptor dysfunction (db/db) and low-density lipoprotein receptor-knockout (LDLR-/-) mice were used. Obese mice were treated with either HQS or vehicle. Blood, liver tissue, white fat tissue and brown adipose tissue were harvested at the end of the treatment. Metabolic disease-related parameters were evaluated to test effects of HQS against diabetes, obesity and hyperlipidemia. Aortic arches from LDLR-/- mice were analyzed to investigate the effects of HQS on atherosclerosis. RNA-sequence, quantitative real-time polymerase chain reaction and Western blot were performed to investigate the mechanisms of HQS against metabolic disorder. RESULTS: HQS lowered body weight, fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice (P < 0.05). HQS also blocked atherosclerotic plaque formation in LDLR-/- mice. HQS suppressed de novo lipid synthesis by reducing the expression of messenger RNA for sterol regulatory element-binding factor 1, stearyl coenzyme A desaturase 1 and fatty acid synthase, and enhancing adenosine 5'-monophosphate-activated protein kinase signaling in both in vivo and in vitro experiments, indicating potential mechanisms for HQS's activity against diabetes. CONCLUSION: HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.

[Epidemiological analysis of liver injury related to bone diseases].

A total of 1 392 reports on liver injury associated adverse drug reaction(LI-ADR) related to bone diseases were retrospectively analyzed based on national ADR monitoring system [18.75% of the patients used traditional Chinese medicine(TCM) alone and 68.68% used Western medicine alone]. This kind of cases accounted for 2.5% of all drug-related liver injury adverse reactions, ranking top ten of all drug categories. The number of reported cases and the proportion of serious cases showed an increasing trend from 2012 to 2016. The average age of the patients was(54.2±15.8) years old, and there was little difference in overall gender(male-female 1.04∶1). However, the number of female patients with rheumatoid arthritis was significantly higher than that of male patients(male-female 1∶2.6), while the number of male patients with gout was significantly higher than that of female patients(male-female 7.16∶1). The overall prognosis was good, with the recovery and improvement rate of 85.27%. The time from medication to liver injury varied due to different medicines. The median time to liver injury was 27 days in TCM alone group, later than 11 days in Western me-dicine alone group(P<0.05). Drugs for bone diseases have been one of the important categories for clinical drug-induced liver injury, and the number of reported cases on liver injury caused by drugs for bone diseases is increasing, so we should pay close attention to the safe and rational use of them. The LI-ADRs of male and female were different due to their different diseases, and the latency of adverse reactions in TCM group was generally longer than that in Western medicine group. In clinical medication, liver function should be monitored according to different diseases and characteristics of drugs to prevent the risk of liver injury.

Performance, kinetics characteristics and enhancement mechanisms in anammox process under Fe(II) enhanced conditions.

In order to explore the performance, kinetics characteristics and enhancement mechanisms in anammox process under ferrous iron enhanced conditions, a laboratory-scale UASB anammox reactor has been built up and operated for 534 days. Experimental results showed that the Anammox process was successfully started up in a short operation period and the TNRE reached 83.34 ± 2.96% with a maximum total nitrogen removal rate of 14.4 kg m-3 d-1 after long-term operated under influent Fe(II) concentration of 5.3 mg L-1. Simulation results using different kinetic models showed that the Stover-Kincannon model and the Grau second-order model were useful for describing the anammox performance under Fe(II) enhanced conditions. Extracellular polymeric substance (EPS) act a pivotal part in the granulation of Anammox sludge and the improvement of anammox activity. Iron improved the hydrophobicity of the sludge by reducing the PN/PS ratios, and also increased the Anammox granular diameter. The granular diameter of higher than 2.00 accounted for 58.3% of the total sludge. At the same time, the presence of iron decreased EPS levels, and also decreased the iron adsorption ability to sludge. More iron was transported into Anammox, which improved the nitrogen removal ability in the Anammox reactor.

Screening for Susceptibility-Related Factors and Biomarkers of Xianling Gubao Capsule-Induced Liver Injury.

Although increasing reports from the literature on herbal-related hepatotoxicity, the identification of susceptibility-related factors and biomarkers remains challenging due to idiosyncratic drug-induced liver injury (IDILI). As a well-known Chinese medicine prescription, Xianling Gubao Capsule (XLGB) has attracted great attention due to reports of potential liver toxicity. But the mechanism behind it is difficult to determine. In this paper, we found that XLGB-induced liver injury belongs to IDILI through the analysis of clinical liver injury cases. In toxicological experiment assessment, co-exposure to XLGB and non-toxic dose of lipopolysaccharide (LPS) could cause evident liver injury as manifested by significantly increased plasma alanine aminotransferase activity and obvious liver histological damage. However, it failed to induce observable liver injury in normal rats, suggesting that mild immune stress may be a susceptibility factor for XLGB-induced idiosyncratic liver injury. Furthermore, plasma cytokines were determined and 15 cytokines (such as IL-1ß, IFN-γ, and MIP-2α etc) were acquired by receiver operating characteristic (ROC) curves analysis. The expression of these 15 cytokines in LPS group was significantly up-regulated in contrast to the normal group. Meanwhile, the metabolomics profile showed that mild immune stress caused metabolic reprogramming, including sphingolipid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. 8 potential biomarkers (such as sphinganine, glycerophosphoethanolamine, and phenylalanine etc.) were identified by correlation analysis. Therefore, these results suggested that intracellular metabolism and immune changes induced by mild immune stress may be important susceptibility mechanisms for XLGB IDILI.

[Re-evaluation of liver injury associated with Buguzhi Preparations based on passive monitoring data and hospital cases].

In this paper,the case reports on rug-induced liver injury( ADR cases) related to Gukang Capsules containing Psoralea corylifolia( Buguzhi,BGZ) were collected from the adverse reaction monitoring database from January 1,2012 to December 31,2016,and the in-patients cases with drug-induced liver injury admitted to a tertiary Class A liver disease hospital from January 1,2010 to December 31,2016 were also collected. These collected cases were re-evaluated and analyzed. 110 cases with liver injury related to this preparation were collected from adverse reaction monitoring database,and 55 cases of them received the preparation alone,mainly for fracture treatment( 52. 74%). Ninty one cases( 82. 72%) met the standard of the biochemical diagnostic criteria for drug-induced liver injury. 89. 01% of patients were over the age of 41 and women accounted for 60. 9%. The time from administration to liver injury was 1-208 days,with the median of 29 d. The dose of the preparation was 2. 4-4. 8 g per day,with a cumulative dose ranging from 3. 6-699. 6 g. The recovery and improvement rate reached 96. 70% after positive treatment. Seven inpatient cases related to the preparation were collected in a tertiary Class A liver disease hospital,6 females and 1 male. All of them were over 40 years old. Two cases reached the " suspicious diagnosis" standard and 5 cases reached the " clinical diagnosis" standard in Guidelines for the diagnosis and treatment of herb-induced liver injury. Six patients had a good prognosis effect,but another one had liver failure. This preparation is commonly used in fracture,osteoarthritis and other diseases,with remarkable curative effect. However,ADR cases and hospital cases all indicated the risk of liver injury. There was no significant correlation between the time and dose of drug use and the occurrence of liver injury.The induced-liver injury may have immunological heterogeneity,thus regular monitoring of liver function should be taken during clinical use.