The therapeutic effects of traditional Chinese medicine on insulin resistance in obese mice by modulating intestinal functions.

Introduction: Obesity, mainly caused by excessive accumulation of visceral fat, excessive fat metabolism will cause hormone secretion imbalance and inflammation and other diseases. is extremely detrimental to human health. Although many treatments are available for obesity, most treatments fail to exert a radical effect or are associated with several side effects. Traditional Chinese medicine (TCM) for regulating the intestinal flora, lipid content and inflammation is considered effective. Based on previous studies, Artemisia capillaris, Astragalus propinquus, Phellodendron amurense, Salvia miltiorrhiza, Poria cocos, and Anemarrhena asphodeloides were selected to prepare an innovative herbal formula. Methods: TCM was characterized by UHPLC-Q-Orbitrap-MS. The anti-inflammatory and lipid-lowering effects of the TCM formula prepared were evaluated in a high-fat diet-fed obese mouse model. The effects of the TCM formula on the intestinal flora were also investigated. Results: Weights and insulin resistance, as well as inflammation, decreased in the mice after treatment. At the same time, lipid metabolism increased after the mice were gavaged with the TCM formula for 2 weeks. The intestinal motility of the drug administration group was enhanced, with partial restoration of the intestinal flora. Conclusion: In summary, our innovative Chinese herbal formula significantly reduced weight, reduced intestinal inflammation, improved intestinal motility, and improved lipid metabolism in obese mice. Furthermore, the innovative formula effectively prevented relevant obesity-induced metastatic diseases in the mice.

Loss of QKI in macrophage aggravates inflammatory bowel disease through amplified ROS signaling and microbiota disproportion.

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.

Obacunone Attenuates Liver Fibrosis with Enhancing Anti-Oxidant Effects of GPx-4 and Inhibition of EMT.

Obacunone, a limonin triterpenoid extracted from Phellodendronchinense Schneid or Dictamnus dasycarpusb Turcz plant, elicits a variety of pharmacological effects such as anti-inflammatory, anti-neoplastic, anti-oxidation, and anti-lung-fibrosis ones. However, the anti-fibrotic effect of obacunone and the detailed underlying mechanism in liver fibrosis remain unclear. Liver fibrosis is a debilitating disease threatening human health. Transforming growth factor (TGF)-ß/P-Smad is a major pathway of fibrosis featured with epithelia mesenchymal transformations (EMT) and collagen depositions, accompanying with excessive oxygen-free radicals. Nrf-2 acts as a key anti-oxidative regulator driving the expressions of various antioxidant-related genes. Glutathionperoxidase-4 (GPx-4) is a member of the glutathione peroxidase family that directly inhibits phospholipid oxidation to alleviate oxidative stress. In the present study, we aimed to explore the role of obacunone in mouse liver fibrosis model induced by carbon tetrachloride (CCl4) and in hepatic stellate cells (LX2 cell line) challenging with TGF-ß. Obacunone demonstrated potent ameliorative effects on liver fibrosis both in activated LX2 and in mice liver tissues with reduced levels of α-SMA, collagen1, and vimentin. Obacunone also remarkably suppressed the TGF-ß/P-Smad signals and EMT process. Meanwhile, obacunone exerted a potent anti-oxidation effect by reducing the levels of reactive oxygen species (ROS) in both models. The antioxidant effect of obacunone was attributed to the activation of GPx-4 and Nrf-2. In addition, the therapeutic effect of obacunone on LX2 cells was significantly removed in vitro plus with GPx-4 antagonist RSL3, in parallel with the re-elevated levels of ROS. Thus, we demonstrate that obacunone is able to attenuate liver fibrosis via enhancing GPx-4 signal and inhibition of the TGF-ß/P-Smad pathway and EMT process.

[Prevalence of blindness and moderate and severe visual impairment among adults aged 50 years or above in Ji'an county of Jiangxi province:the China Nine-Province Survey].

OBJECTIVE: To investigate the prevalence of blindness and moderate and severe visual impairment among adults aged 50 years or above in Ji'an county of Jiangxi province, China. METHODS: It was a population-based cross-section study. Geographically defined cluster sampling was used in 5402 randomly selected individuals aged ≥ 50 years in 28 clusters in Ji'an from September to November 2006. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. All participants were enumerated through village registers followed door-to-door visits. Eligible individuals were invited to receive visual acuity measurement and eye examination. Statistical analyses were performed using Stata/SE Statistical Software, release 9.0. Chi-square test was used to investigate the association of age, gender and education with presenting and best corrected visual acuity. RESULTS: Five thousands four hundreds and two individuals were enumerated and 5010 persons were examined, the response rate was 92.74%. Based on the criteria of World Health Organization visual impairment classification in 1973, 78 persons were diagnosed as blindness, 265 persons were diagnosed as moderate and severe visual impairment defined as best corrected visual acuity, the prevalence of blindness and moderate and severe visual impairment were 1.56% and 5.29% respectively. Ninety-four persons were diagnosed as blindness, 726 persons were diagnosed as moderate and severe visual impairment defined as presenting visual acuity, the prevalence of blindness and moderate and severe visual impairment defined as presenting visual acuity was 1.88% and 14.50% respectively. The prevalence of blindness and moderate and severe visual impairment was higher in aged (trend χ(2) = 970.15, P = 0.000), female (χ(2) = 89.81, P = 0.000), and illiterate persons (trend χ(2) = 241.85, P = 0.000). Cataract was still the first leading cause of blindness and visual impairment, the retinal diseases was the second. Un-corrected refractive error also was the main cause of visual impairment. CONCLUSIONS: The prevalence of blindness and moderate and severe visual impairment was higher than other district in China. The first leading cause of blindness and visual impairment is still cataract.

[Prevalence of blindness and low vision among adults aged 50 years or above in Ji'an county of Jiangxi province: the China nine-province survey].

OBJECTIVE: To estimate the prevalence of cataract, the outcomes of cataract surgery, cataract surgical coverage rate, cataract blindness social burden rate in Ji'an county of Jiangxi province, China. METHODS: Cluster sampling was used in randomly selected 5010 individuals aged ≥ 50 years in Ji'an county of Jiangxi province. All individuals were received visual acuity and eye examination, including the evaluation of lens status and cataract surgical status by slit lamp biomicroscopy. Data bank was established by Epi-info Software. Statistical analyses were performed using Stata/SE Statistical Software, release 9.0 (Stata Corp, College Station, TX). Confidence intervals and P values (considered significance at the P < 0.05 level) for prevalence of cataract, cataract surgical coverage rate, cataract blindness social burden rate and outcomes of surgery were calculated with adjustment for clustering effects and stratification associated with the sampling design. RESULTS: In 5010 individuals, 1158 cases of cataract were found, the prevalence of cataract was 23.11% among adults aged 50 or above. The prevalence of cataract was higher in the aged, female (P < 0.01). In 99 eyes with cataract surgery, 50.51% and 5.05% of eyes were performed by the modern extra-capsular surgery and phacoemulsification respectively. The rate of intraocular lens implantation was 55.56%. Post-operative presenting and best corrected visual acuity equal to or more than 0.7 was 10.1% and 45.5% of operated eyes respectively. The main causes of the post-operated eyes with worse visual acuity were post-capsular opacity and refractive error. The cataract surgical coverage rate was 32.29%, and the cataract blindness social burden rate was 3.83%. The cataract surgical rate was lower and cataract blindness social burden rate was higher in the aged persons (P < 0.01). CONCLUSIONS: Cataract is the most common eye disease that may lead into blindness and severe visual impairment among older adults aged equal or more than 50 years. The cataract surgical coverage rate is not high but the cataract blindness social burden rate is heavy in Ji'an county. The rate of intraocular lens implantation need increase and the visual outcomes of the surgery should be further improved in the future.