Metformin protects 5-Fu-induced chemotherapy oral mucositis by reducing endoplasmic reticulum stress in mice.

Metformin (Met) is a first-line and essential treatment for type 2 diabetes, with anti-inflammatory effects. It has been reported Met could inhibit NF-κB activity and down-regulate the release of inflammatory factors. However, whether Met has a protective effect on chemotherapy-induced oral mucositis(CIOM) is unknown. The purpose of this study was to evaluate the protective effect of Metformin(Met) on chemotherapy-induced oral mucositis(CIOM) and further explore its possible mechanism. 5-Fu was used in the C57BL/6 mice to establish the model of CIOM. Our results showed Met could significantly improve 5-Fu-induced mucosal damage, apoptosis, ROS and releasing of inflammatory factors in the tongue tissue. In addition, Met could inhibit 5-Fu-induced high expression of endoplasmic reticulum stress(ERS)-related proteins GRP78 and CHOP. Further studies showed that the protective effect of ERS inhibitor 4-PBA on CIOM was similar to Met. Moreover, Met inhibited the phosphorylation of NF-κB in tongue tissue, independent of AMPK phosphorylation. The protective effect of PDTC, an inhibitor of NF-κB, on tongue tissue was similar to that of Met. This study confirmed the protective effect of Met on 5-Fu-induced CIOM, which was achieved by inhibiting ERS and reducing the activity of NF-κB.

Protective effect of endoplasmic reticulum stress inhibition on 5-fluorouracil-induced oral mucositis.

5-Fluorouracil (5-FU)-induced oral mucositis has a severe negative impact on the patient's quality of life. This study aimed to investigate the role of endoplasmic reticulum stress (ERS) in the occurrence of 5-FU-induced oral mucositis in vivo and in the clinic. In vivo, 5-FU-induced oral mucositis model mice showed a higher level of glucose-regulated protein 78 kD (GRP78, a marker of ERS) than control mice. The inhibition of ERS could effectively reduce 5-FU-induced oxidative stress, inflammatory factor mRNA and cell apoptosis. Moreover, inhibition of ERS significantly decreased the activation of nuclear factor kappa-B (NF-κB) in 5-FU-induced oral mucositis model mice following tissue damage reduction. In the clinic, 5-FU could increase cell apoptosis and cause oral mucosa damage while increasing the expression of the ERS marker genes GRP78 and C/EBP-homologous protein (CHOP). Our study found that 5-FU could induce severe ERS, upregulate the expression of GRP78 and CHOP, raise oxidative stress and increase the expression of inflammatory factors by activating the NF-κB pathway, thus causing cell apoptosis and finally leading to oral mucosal injury.

Efficient recovery of phosphate from simulated urine by Mg/Fe bimetallic oxide modified biochar as a potential resource.

The massive use of phosphate fertilizers in agriculture is costly and induces water pollution, calling for more sustainable phosphate sources in the context of the circular economy. Here we prepared a new adsorbent based on waste straw biochar modified with the Mg/Fe bimetallic oxide, namely the Mg/Fe biochar, to recover phosphate from the simulated urine as an possible phosphate fertilizer. About 90% phosphate was recovered from the simulated urine with a wide pH range of 3.0-9.0 and a maximum adsorption capacity of 206.2 mg/g, using 1 g/L of Mg/Fe modified biochar. A pseudo second-order kinetics and Sips model were proposed to fit the experimental data well, suggesting that the adsorption was controlled by physical and chemical processes, which is driven by electrostatic attraction, intra-particle diffusion, ion exchange and surface ligand exchange. Overall, the Mg/Fe biochar is renewable and can recover more than 70% of phosphate in the simulated urine after 5 cycles of reuse, which appears as a safe and efficient adsorbent to recycle phosphate from urine.

Internet Influence of Assisted Reproduction Technology Centers in China: Qualitative Study Based on WeChat Official Accounts.

BACKGROUND: The prevalence of infertility in China is high, but the advent of assisted reproduction technology (ART) has greatly eased this situation. Social media, such as WeChat official accounts, have become the preferred tool for ART centers to communicate with patients, but their attention and operational status differ, and the Internet influence of WeChat official accounts is insufficient. In addition, questions about whether Internet influence is consistent with academic influence and whether the Internet can influence patients' choice of medical treatment to a certain extent have not been explored. OBJECTIVE: This study aimed to examine the operational status and Internet influence of WeChat official accounts for ART centers and to explore the degree of Internet influence on patients' choices of medical treatment. METHODS: We collected information from the WeChat official accounts for ART centers approved by the National Health Commission of the People's Republic of China and used the technique for order of preference by similarity to ideal solution to build an Internet influence model of the ART centers and obtained a Ranking of Internet Influence on Reproductive Centers (RIIRC) for each center. RESULTS: We found there were 451 ART centers throughout the country by the end of 2016 and 498 by the end of 2018. The number of medical institutions is quite large, but their distribution is uneven, and their level of medical technical ability is very different. Analysis of the text data of posts of WeChat official accounts showed the ART centers have insufficient awareness of network exposure and publicity, and the RIIRC of some medical institutions was inconsistent with their medical level and academic status. CONCLUSIONS: ART institutions have varying degrees of emphasis and use of WeChat official accounts in China. They fail to realize that the Internet influence of WeChat may bring them potential patient resources and that Internet influence may affect the future market structure of ART and may also potentially affect academic rankings.

Association between atherosclerosis and gastric biomarkers concerning Helicobacter pylori infection in a Chinese healthy population.

BACKGROUND: Studies have suggested that Helicobacter pylori (Hp) infection is associated with atherosclerotic process, while the relationship between pepsinogens, gastrin and atherosclerosis is unknown. AIM: The aim of the study was to observe association of Hp infection on atherosclerotic parameters and blood pressure, and explore the relationship between atherosclerotic parameters, blood pressure and gastric biomarkers in a healthy population. METHODS: 395 subjects were chosen and received physical examinations, carotid artery ultrasound, peripheral atherosclerosis measurement, and testing of serum pepsinogen (PG) I and II, Hp antibody, and gastrin-17 (G-17) levels. Analyses were conducted by Student's t-test, ANOVA, Pearson correlation, multiple linear regression and binary logistic regression. RESULTS: In Hp-infected subjects, right carotid intima media thickness (R-CIMT) were higher (P = 0.027) and left ankle brachial index were higher in 45-64 years compared to 35-44 years group (P = 0.039, P = 0.016). Hp-IgG, PGI and G-17 respectively positively correlated with CIMT, pulse wave velocity and systolic blood pressure (P = 0.044, P = 0.013, P = 0.021). The unadjusted OR in subjects with elevated CIMT for quartile IV of PGI was 3.542 (95% CI, 1.491-8.411), the adjusted OR was 2.916 (95% CI, 1.035-8.216). The unadjusted OR in subjects with elevated CIMT for quartile III of G-17 was 4.351 (95% CI, 1.670-11.336) and for quartile IV was 3.108 (95% CI, 1.149-8.406), the adjusted OR for quartile III was 4.962 (95% CI, 1.515-16.258). CONCLUSIONS: Hp infection, higher levels of PGI and G-17 may contribute to atherosclerotic process by influencing atherosclerotic parameters and blood pressure in a healthy population, the influence on CIMT was most significant.

Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese population.

AIM: To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori (H. pylori) infection in a healthy population, and explore factors associated with gastric biomarkers. METHODS: Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen (PG) I and II, gastrin-17 (G-17) and H. pylori antibody levels. Analyses were made by Student's t-test, ANOVA, Pearson's correlation and multiple linear regressions. RESULTS: PGII levels were higher in the ≥ 65-years-old age group (P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group (P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol (LDL-C) were higher (P = 0.009) in H. pylori-infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group (P < 0.05) for H. pylori-infected subjects and 45-64-years-old age group (P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-IgG level positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII (P < 0.001). Creatinine positively correlated with PGI, PGII and G-17 (P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose (FBG) positively correlated with PGI/PGII and G-17 (P < 0.001, P = 0.037). Age positively correlated with PGII and G-17 (P = 0.005, P = 0.026). CONCLUSION: PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin.

Honokiol inhibits tumor necrosis factor-α-stimulated rat aortic smooth muscle cell proliferation via caspase- and mitochondrial-dependent apoptosis.

This study aims to investigate the effects of honokiol on proliferation, cell cycle, and apoptosis in tumor necrosis factor (TNF)-α-induced rat aortic smooth muscle cells (RASMCs). We found that honokiol treatment showed potent inhibitory effects on TNF-α-induced RASMC proliferation, which were associated with G0/G1 cell cycle arrest and downregulation of cell cycle-related proteins, including cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2 and CDK4. Furthermore, honokiol treatment led to the release of cytochrome c into cytosol and a loss of mitochondrial membrane potential (ΔΨm), as well as a decrease in the expression of Bcl-2 and an increase in the expression of Bax. Treatment with honokiol also reduced TNF-α-induced phosphorylation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase. Taken together, our results suggest that honokiol suppresses TNF-α-stimulated RASMC proliferation via caspase- and mitochondria-dependent apoptosis and highlight the therapeutic potential of honokiol in the prevention of cardiovascular diseases.