EGFR/MAPK signaling pathway acts as a potential therapeutic target for sulforaphane-rescued heart tube malformation induced by various concentrations of PhIP exposure.

BACKGROUND: 2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyrimidine (PhIP) is a known carcinogen generated mainly from cooking meat and environmental pollutants. It is worth exploring the potential of natural small-molecule drugs to protect against adverse effects on embryonic development. PURPOSE: In this study, we investigated the potential toxicological effects of PhIP on embryonic heart tube formation and the effect of Sulforaphane (SFN) administration on the anti-toxicological effects of PhIP on embryonic cardiogenesis. STUDY DESIGN AND METHODS: First, the chicken embryo model was used to investigate the different phenotypes of embryonic heart tubes induced by various concentrations of PhIP exposure. We also proved that SFN rescues PhIP-induced embryonic heart tube malformation. Second, immunofluorescence, western blot, Polymerase Chain Reaction (PCR) and flow cytometry experiments were employed to explore the mechanisms by which SFN protects cardiac cells from oxidative damage in the presence of PhIP. We used RNA-seq analysis, molecular docking, in situ hybridization, cellular thermal shift assay and solution nuclear magnetic resonance spectroscopy to explore whether SFN protects cardiogenesis through the EGFR/MAPK signaling pathway. RESULTS: The study showed that PhIP might dose-dependently interfere with the C-looping heart tube (mild) or the fusion of a pair of bilateral endocardial tubes (severe) in chick embryos, while SFN administration prevented cardiac cells from oxidative damage in the presence of high-level PhIP. Furthermore, we found that excessive reactive oxygen species (ROS) production and subsequent apoptosis were not the principal mechanisms by which low-level PhIP induced malformation of heart tubes. This is due to PhIP-disturbed Mitogen-activated protein kinase (MAPK) signaling pathway could be corrected by SFN administration. CONCLUSIONS: This study provided novel insight that PhIP exposure could increase the risk of abnormalities in early cardiogenesis and that SFN could partially rescue various concentrations of PhIP-induced abnormal heart tube formation by targeting EGFR and mediating EGFR/MAPK signaling pathways.

Meta-analysis-based systematic review of effect of traditional Chinese medicine intervention in treatment of diabetic nephropathy on thyroid function.

BACKGROUND: This research sought to systematically evaluate the clinical effects of traditional Chinese medicine (TCM) intervention in the treatment of diabetic nephropathy (DN) and analyze changes in thyroid function in patients with DN. METHODS: The PubMed, Embase, Medline, Ovid, Springer, and self-built databases were searched to screen literature on TCM intervention and the treatment of DN published from the establishment of the databases to January 1, 2021. The Cochrane Handbook for Systematic Reviews of Intervention 5.0.2 was then employed to assess the risk of bias in literature, and Review Manager 5.3 was utilized for the meta-analysis. RESULTS: A total of 20 randomized controlled trials (RCTs) were included in the study, involving 3,566 subjects, and meta-analysis results showed that the clinical treatment efficiency of the experimental group was dramatically higher than the control group [MD =6.22, 95% confidence interval (CI): 3.77-10.25, Z=7.17, P<0.00001]. Moreover, the serum creatinine (Scr), blood urea nitrogen (BUN), urine protein excretion rate (UAER), 24 h postoperative urine protein quantification, and tumor necrosis factor-alpha (TNF-α) of patients after TCM intervention were all remarkably inferior to those of the control group as seen in the following results: Scr, MD =-8.69, 95% CI: -9.92 to -7.47, Z=13.94, P<0.00001; BUN, MD =-1.74, 95% CI: - 2.48 to -1.00, Z=4.6, P<0.00001; UAER, MD =-26.16, 95% CI: -46.89 to -5.44, Z=2.47, P=0.01; 24 h postoperative urine protein quantification, MD =-0.54, 95% CI: -0.68 to -0.4, Z=7.4, P<0.00001; TNF-α, MD =-5.3, 95% CI: -9.15 to -1.46, Z=2.7, P=0.007; and high sensitivity C-reactive protein (hs-CRP), MD =-1.34, 95% CI: -1.9 to -0.78, Z=4.66, P<0.00001. DISCUSSION: TCM intervention in DN is effective in treating the clinical symptoms of patients with this disease and has ideal therapeutic effects.

Effects of Shenqi compound on intestinal microbial metabolites in patients with type 2 diabetes: A protocol for systematic review and meta analysis.

INTRODUCTION: According to the data from the 2017 Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes [Chin J Diabetes. 2017;20:81-117], in 2013, the incidence of T2DM in China was 10.4%, while nearly 63% of the patients did not receive standard diagnosis. T2DM has become a serious public health problem in China and even in the world. Intestinal flora, as a research hotspot related to T2DM and other diseases in recent years, is a kind of microorganism with a large number in the human intestinal tract, which is considered as one of the important factors affecting the metabolism of the endocrine system and the human internal environment. In fact, many concepts of traditional Chinese medicine (TCM) coincide with modern research results of intestinal flora. In fact, TCM is also widely used to regulate intestinal flora disorders, and plays a very important role in restoring the dysfunctional intestinal flora [Hu et al. Drug Eval. 2013:8-10]. T2DM is a chronic systemic progressive disease. Studies [Wang et al. Tianjin Chin Med. 2007;24:507-508] have shown that even ideal blood glucose control cannot prevent the failure of islet cells [Wang et al. Tianjin Chin Med. 2007;24:507-508], and how to restore the function and number of islet cells has naturally become the focus and difficulty of our current research. Studies have shown that the changes in the contents of intestinal microflora and their metabolites are closely related to the performance of T2DM such as hyperglycemia, insulin resistance, and restoration of islet function, and play an important role in pathophysiological mechanisms such as chronic inflammation of T2DM [Sun et al. Shi Zhen Chin Med. 2012;23:1434-1436]. It has been confirmed that Shenqi compound, a TCM, regulates intestinal flora of T2DM. However, due to the lack of evidence, there is no specific method or suggestion, it is necessary to make a systematic evaluation of Shenqi compound to provide effective evidence for further research. METHODS AND ANALYSIS: Electronic databases included PubMed, Embase, Cochrane Library, Web of Science, Nature, Science Online, WanFang China Biomedical Database, VIP Medical Information, China national Knowledge Infrastructure (CNKI). MAIN RESULTS: Endotoxin, short-chain fatty acid, bile acid, indole.Other results: low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), total serum cholesterol (TC). The data will be extracted independently by 2 researchers, and the risk of bias in the meta-analysis will be systematically evaluated according to the Cochrane handbook. All data analysis will be performed using the Data statistics software Review Manager V.5.3. And occupy V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of Shenqi compound on the effects of intestinal flora metabolites in patients with type 2 diabetes. CONCLUSION: Through the systematic review of this study, the published evidence of the effect of Shenqi compound on intestinal flora metabolites in patients with type 2 diabetes was summarized to further guide its promotion and application. ETHICS AND COMMUNICATION: This study is a systematic review with findings based on published evidence and does not require erB review or consent. We plan to publish the results in a journal or conference report. OPEN SCIENCE FRAMEWORK (OSF) REGISTRATION NUMBER: September 29, 2020. osf.io/gb3m2.(https://osf.io/gb3m2).

Acupuncture for thyroid nodule treatment: A protocol of systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Thyroid nodules are scattered lesions caused by abnormal local growth of thyroid cells. In recent years, their prevalence rate has been rising gradually, and the probability of cancerations has also been increasing gradually. Therefore, we must pay more attention to them and carry out early intervention. However, at present, most of the intervention measures for patients with thyroid nodules are mainly clinical observation and follow-up, and no clear and effective drug intervention therapy has been proposed. The curative effect of acupuncture on thyroid nodules has been proved clinically. However, as there is no clear mechanism of action, no specific operation methods or Suggestions, it is necessary to make a systematic evaluation of acupuncture therapy, so as to lay a foundation for further research in the future. METHODS AND ANALYSIS: The following databases will be searched from their inception to June 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WanFang, VIP medicine information, and China National Knowledge Infrastructure (CNKI). Primary outcomes: Color ultrasound of thyroid and cervical lymph nodes, FT3, FT4, TSH, TGAB, TPOAB, insulin resistance index (HOMA-IR). Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the efficacy and safety of acupuncture therapy for patients with thyroid nodule. CONCLUSION: Through the systematic review of this study, the evidence of the treatment of thyroid nodule by acupuncture has been summarized so far, so as to provide guidance for further promoting the application of acupuncture therapy in patients with thyroid nodule. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRA NETWORK (OSF) REGISTRATION NUMBER: August 18, 2020. osf.io/uzck4. (https://osf.io/uzck4).

Treatment of microcirculation dysfunction in type 2 diabetic mellitus with Shenqi compound prescription: A protocol of systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Type 2 diabetic mellitus (T2DM) is a chronic disease. In 2013, the International Diabetes Federation showed that the total number of diabetic patients aged 20 to 79 years in China was 89 million, and it is expected to increase to 143 million by 2035. The incidence of T2DM and its complications in patients with blood glucose is gradually increasing, and there are low awareness rate, low diagnosis rate and high disability rate, which has become a global public health problem. Microcirculation Dysfunction in Type 2 diabetic mellitus (MDT2DM) plays an important role in the development of diabetic nephropathy, diabetic retinopathy, diabetic neuropathy and diabetic foot disease. It is 1 of the common etiological mechanisms of diabetic chronic complications. Patients with MDT2DM, serious complications, increase the quality of life of patients with social impact. Diabetic lower extremity microcirculation disease (dlemd) is the main cause of the occurrence, development and difficult healing of diabetic foot. Microvascular disease is microcirculation dysfunction. It has been proved that Shenqi compound prescription can treat T2DM macrovascular disease and microvascular dysfunction. However, due to the lack of evidence and no specific methods or suggestions, it is necessary to conduct a systematic evaluation of Shenqi compound prescription to provide effective evidence for further research. METHODS AND ANALYSIS: The following databases will be searched from their inception to August 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WanFang, VIP medicine information, and China National Knowledge Infrastructure. PRIMARY OUTCOMES:: superoxide dismutase, malondialdehyde, C-reactiveprotein, HOMA-IR, advanced glycation end products , FPG, 2hBG, glycosylated hemoglobinA1c, fasting insulin ; ADDITIONAL OUTCOMES:: low density lipoprotein, high density lipoprotein, triglycerides, total serum cholesterol. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the efficacy and safety of Shenqi compound prescription in treating patients with MDT2DM CONCLUSION:: The systematic review of this study will summarize the current published evidence of Shenqi compound prescription in the treatment of MDT2DM, and further guide its popularization and application. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRA MEWORK (OSF) REGISTRATION NUMBER: August 24, 2020.osf.io/es6z7. (https://osf.io/es6z7).

A polysaccharide from green tea (Camellia sinensis L.) protects human retinal endothelial cells against hydrogen peroxide-induced oxidative injury and apoptosis.

Oxidative damage of retinal pigment epithelium (RPE) cells is involved in the pathogenesis age related macular degeneration (AMD). The purpose of this study was to evaluate the potential protective effect of a purified green tea polysaccharide (GTWP) against hydrogen peroxide (H2O2) induced oxidative stress and apoptosis in human retinal pigment epithelial cells (ARPE-19 cells). Human ARPE-19 cells were treated with 1 h of 500 µM H2O2 before incubation with GTWP for 24 h. Pretreatment of GTWP decreased H2O2-induced cell death and cell apoptosis, and efficiently suppressed the intracellular ROS production and malondialdehyde (MDA) generation induced by H2O2 treatment. Moreover, a loss of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) activities were restored to normal level in H2O2-induced ARPE-19 cells upon GTWP (100 µg/ml) exposure. Also, the tendency of increased protein expression of Bax and cleaved-caspsae-3, as well as decrease of Bcl-2 protein in ARPE-19 cells challenged with H2O2 was changed to individual opposite way, thus inhibiting the apoptotic cell death. Our results demonstrated that GTWP protected RPE cells against oxidative injury through activation of anti-apoptotic and endogenous antioxidant enzymes signaling pathway, suggesting GTWP has attractive therapeutic potential to AMD.

Protective effects of rice dreg protein hydrolysates against hydrogen peroxide-induced oxidative stress in HepG-2 cells.

In this paper, the effects of rice dreg protein hydrolysates (RDPHs) obtained by various proteases on hydrogen peroxide-induced oxidative stress in HepG-2 cells were investigated. Cell cytotoxicity was evaluated through the aspects of cell viability, ROS level, antioxidant enzyme activity, and production of malondialdehyde (MDA). Cell apoptosis was assessed by flow cytometry. Molecular weight distribution was analyzed by gel permeation chromatography, and amino acid composition was measured using an automatic amino acid analyzer. The survival of cells and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased through the pre-incubation of HepG-2 cells with RDPHs before H2O2 exposure. Additionally, these pretreatments also resulted in a reduction in ROS and MDA levels. As a result, apoptosis and loss of mitochondrial membrane potential of the HepG-2 cells were alleviated. Furthermore, the protective effects of protein hydrolysates obtained by various proteases were noticeably distinct, in which RDPHs prepared by alkaline protease showed higher antioxidant activities. The difference in the protective effects might be attributed to the specific peptide or amino acid composition. Therefore, enzymatic hydrolysis with different enzymes studied here could attenuate H2O2-induced cell damage, and the type of protease greatly influenced the anti-oxidative activity. Particularly, optimum use of Alcalase could produce peptides with higher antioxidant activity.

Effect of Hops Beta Acids on the Survival of Unstressed- or Acid-Stress-Adapted-Listeria Monocytogenes and on the Quality and Sensory Attributes of Commercially Cured Ham Slices.

This study evaluated the antilisterial activity of hops beta acids (HBA) and their impact on the quality and sensory attributes of ham. Commercially cured ham slices were inoculated with unstressed- and acid-stress-adapted (ASA)-L. monocytogenes (2.2 to 2.5 log CFU/cm(2) ), followed by no dipping (control), dipping in deionized (DI) water, or dipping in a 0.11% HBA solution. This was followed by vacuum or aerobic packaging and storage (7.2 °C, 35 or 20 d). Samples were taken periodically during storage to check for pH changes and analyze the microbial populations. Color measurements were obtained by dipping noninoculated ham slices in a 0.11% HBA solution, followed by vacuum packaging and storage (4.0 °C, 42 d). Sensory evaluations were performed on ham slices treated with 0.05% to 0.23% HBA solutions, followed by vacuum packaging and storage (4.0 °C, 30 d). HBA caused immediate reductions of 1.2 to 1.5 log CFU/cm(2) (P < 0.05) in unstressed- and ASA-L. monocytogenes populations on ham slices. During storage, the unstressed-L. monocytogenes populations on HBA-treated samples were 0.5 to 2.0 log CFU/cm(2) lower (P < 0.05) than control samples and those dipped in DI water. The lag-phase of the unstressed-L. monocytogenes population was extended from 3.396 to 7.125 d (control) to 7.194 to 10.920 d in the HBA-treated samples. However, the ASA-L. monocytogenes population showed resistance to HBA because they had a higher growth rate than control samples and had similar growth variables to DI water-treated samples during storage. Dipping in HBA solution did not adversely affect the color or sensory attributes of the ham slices stored in vacuum packages. These results are useful for helping ready-to-eat meat processors develop operational procedures for applying HBA on ham slices.