Geniposide Attenuates Oxygen-glucose Deprivation/Recovery-induced Retinal Ganglion Cell Injury via Akt/Nrf-2 Signaling Pathway.

BACKGROUND: Glaucoma is an eye disease. Its pathological process involves retinal ischemia-reperfusion (I/R), which causes irreversible blindness in patients. Geniposide (Gen), a bioactive iridoid glycoside extracted from the fruit of gardenia, exhibits many biological effects, such as anti-oxidative stress, anti-inflammation, anti-apoptosis, anti-endoplasmic reticulum stress, and anti-thrombotic effects. However, its therapeutic potential for the retinal I/R injury remains unclear. This study investigated the protective effect of Gen against I/R injury by inhibiting abnormal reactive oxygen species (ROS) and retinal neuron apoptosis. METHODS: We used oxygen-glucose deprivation/reoxygenation (OGD/R) to induce R28 cells to mimic the pathological process of I/R in glaucoma. We conducted CCK-8 analysis and TUNEL staining to examine cell proliferation and apoptosis in glaucoma. Western blotting was used to assay the expressions of apoptosis and Akt/Nrf-2 pathway-related proteins. RESULTS: The production of ROS was detected by using the corresponding kit. Cell viability decreased, whereas TUNEL staining-positive cells and ROS production increased after the OGD/R injury. The contents of cleaved caspase-3 and Bax/Bcl-2 increased after the OGD/R injury. Treatment with 200 µM of Gen effectively improved the cell viability and suppressed cell apoptosis and ROS production. In addition, Gen could significantly promote the activation of the Akt/Nrf-2 signaling pathway in R28 cells, which was blocked by the inhibition of Akt/Nrf-2. We in vivo verified the neuroprotective effect of Gen by establishing an acute high intraocular pressure (aHIOP) model and obtained similar results to those of the in vitro experimental results. CONCLUSION: Hence, it can be suggested that Gen provides neuroprotection against the OGD/R-induced injury of R28 cells by activating the Akt/Nrf-2 signaling pathway, which is beneficial for the clinical treatment of glaucoma.

Effect of an Intermittent Calorie-restricted Diet on Type 2 Diabetes Remission: A Randomized Controlled Trial.

CONTEXT: The 2021 consensus report on the definition and interpretation of remission of type 2 diabetes (T2D) has been released. Although intermittent fasting diets (IF) are becoming very popular, no studies have investigated their benefit in diabetes remission. OBJECTIVE: The present study examined the effectiveness of IF in diabetes remission and potential remission durability. METHODS: Participants between ages 38 and 72 years with a duration of T2D of 1 to 11 years, a body mass index (BMI) of 19.1 to 30.4, 66.7% male, and antidiabetic agent use and/or insulin injection were randomly allocated at a ratio of 1:1 to the Chinese Medical Nutrition Therapy (CMNT) or control group. The primary outcome was diabetes remission, defined as a stable glycated hemoglobin A1c (HbA1c) level of less than 48 mmol/mol (< 6.5%) for at least 3 months after discontinuing all antidiabetic medications. The secondary outcomes included HbA1c level, fasting blood glucose level, blood pressure, weight, quality of life, and medication costs. We conducted a 12-month follow-up to assess the continuation of remission. RESULTS: On completing the 3-month intervention plus 3-month follow-up, 47.2% (17/36) of participants achieved diabetes remission in the CMNT group, whereas only 2.8% (1/36) of individuals achieved remission in the control group (odds ratio 31.32; 95% CI, 2.39-121.07; P < 0.0001). The mean body weight of participants in the CMNT group was reduced by 5.93 kg (SD 2.47) compared to 0.27 kg (1.43) in the control group. After the 12-month follow-up, 44.4% (16/36) of the participants achieved sustained remission, with an HbA1c level of 6.33% (SD 0.87). The medication costs of the CMNT group were 77.22% lower than those of the control group (60.4/month vs 265.1/month). CONCLUSION: This study demonstrated the clinical efficacy of CMNT in achieving diabetes remission for at least 1 year.

Multiomic analysis of dark tea extract on glycolipid metabolic disorders in db/db mice.

Glycolipid metabolic disorder is a serious threat to human health. Dark tea is a kind of traditional Chinese tea, which may regulate the glycolipid metabolic disorders. Dark tea extract (DTE) is the water extraction obtained from dark tea. Compared with traditional dark tea, DTE has the benefits of convenient consumption and greater potential for promoting health. However, the regulation of DTE on glycolipid metabolism and its molecular mechanism is rarely investigated. In our study, DTE was used as raw material to study the effect and molecular mechanism of its intervention on the glycolipid metabolic in db/db diabetic mice by using multiomics analysis and modern biological techniques. (1) DTE could significantly reduce fasting glucose in diabetic db/db mice, and the higher dose group has a better effect. Histopathological examination showed that DTE slightly improve the number of islets and decrease the number of islet ß cells in the pancreatic tissue in db/db mice. (2) RNA-Seq was used to analyze the gene expression in liver tissue. In terms of biological processes, DTE mainly affected the inflammation and fatty acid metabolism. In terms of cell components, the lipoprotein and respiratory chain are mainly affected. In the aspect of molecular function, DTE mainly affected the redox related enzyme activity, iron ion binding and glutathione transferase. Arachidonic acid metabolism pathway, glutathione metabolism and PPAR signaling pathway were enriched by DTE with the results of KEGG pathway enrichment. In addition, real-time PCR results confirmed that DTE could significantly activate key genes of PPAR signaling pathway like Fabp1, Cyp4a1, Ehhadh, Cyp4a32, Aqp7 and Me1. (3) 16s rDNA showed that DTE could significantly decrease the ratio of Firmicutes/Bacteroidetes and the abundance of Proteobacteria, and increased the relative abundance of Verrucomicrobia at the phylum level. At the genus level, the relative abundance of Akkermansia, Prevotellaceae, Bacteroides and Alloprevotella was significantly increased after DTE treatment. This study provides multiomics molecular evidence for the intervention effect of DTE on abnormal glucose and lipid metabolism and the application of precise nutritional diet intervention of dark tea extract.

Research Trends, Hot Spots, and Prospects for Traditional Chinese Medicine in the Field of Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) injury is one of the most common phenomena in ischemic disease or processes that causes progressive disability or even death. It has a major impact on global public health. Traditional Chinese medicine (TCM) has a long history of application in ischemic diseases and has significant clinical effect. Numerous studies have shown that the formulas or single herbs in TCM have specific roles in regulating oxidative stress, anti-inflammatory, inhibiting cell apoptosis, etc., in I/R injury. We used bibliometrics to quantitatively analyze the global output of publications on TCM in the field of I/R injury published in the period 2001-2021 to identify research hotspots and prospects. We included 446 related documents published in the Web of Science during 2001-2021. Visualization analysis revealed that the number of publications related to TCM in the field of I/R injury has increased year by year, reaching a peak in 2020. China is the country with the largest number of publications. Keywords and literature analyses demonstrated that neuroregeneration is likely one of the research hotspots and future directions of research in the field. Taken together, our findings suggest that although the inherent limitations of bibliometrics may affect the accuracy of the literature-based prediction of research hotspots, the results obtained from the included publications can provide a reference for the study of TCM in the field of I/R injury.