Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review

The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.     

Timing of Breastfeeding Initiation Mediates the Association between Delivery Mode,Source of Breastfeeding Education,and Postpartum Depression Symptoms

Background: Emergency cesarean section (EMCS) and breastfeeding difficulties increase the risk of postpartum depressive (PPD) symptoms. Early initiation of breastfeeding (EIBF) may not only alleviate PPD symptoms but also facilitate subsequent breastfeeding success. EMCS is a risk factor for not practicing EIBF. Therefore, it is important to understand the relationship between EMCS, EIBF, and PPD symptoms. Methods: We conducted a prospective cohort study in three areas of China. At baseline, a total of 965 mothers completed electronic questionnaires within 72 h postpartum. Women were screened for PPD symptoms using the Edinburgh Postpartum Depression Scale (EPDS). Multivariate logistic regression was used to identify the determinants of PPD symptoms. Mediation analysis was used to determine if EIBF mediated the relationship between delivery mode or breastfeeding education source and PPD symptoms. Results: The prevalence of EIBF was 40.6%; 14% of 965 mothers experienced EMCS, and 20.4% had PPD symptoms. The risk factors for developing PPD symptoms were excessive gestational weight gain (adjusted odds ratio [aOR] = 1.55, confidence interval [95% CI]: 1.03–2.33, p = 0.037) and EMCS (aOR = 2.05, 95% CI: 1.30–3.25, p = 0.002). The protective factors for developing PPD symptoms were monthly household income over CNY 10000 (aOR = 0.68, 95% CI: 0.47–0.97, p = 0.034), EIBF (aOR = 0.49, 95% CI: 0.34–0.72, p < 0.001), and prenatal breastfeeding education from nurses (aOR = 0.46, 95% CI: 0.29–0.73, p = 0.001). EIBF indirectly affected PPD symptoms in patients who had undergone EMCS (percentage mediated [PM] = 16.69, 95% CI: 7.85–25.25, p < 0.001). The source of breastfeeding education through EIBF also affected PPD symptoms (PM = 17.29, 95% CI: 3.80–30.78, p = 0.012). Conclusion: The association between EMCS on PPD symptoms was mediated by EIBF. By providing breastfeeding education, nurses could also help alleviate PPD symptoms.     

Multilevel mechanism of immune checkpoint inhibitor action in solid tumors: History,present issues and future development

Immunotherapy with checkpoint inhibitors (antibodies that target and block immune checkpoints in the tumor microenvironment) is included in the standard of care for patients with different types of malignancy, such as melanoma, renal cell and urothelial carcinoma, lung cancer etc. The introduction of this new immunotherapy has altered the view on potential targets for treatment of solid tumors from tumor cells themselves to their immune microenvironment; this has led to a reconsideration of the mechanisms of tumor-associated immunity. However, only a subset of patients benefit from immunotherapy and patient response is often unpredictable, even with known initial levels of prognostic markers; the biomarkers for favorable response are still being investigated. Mechanisms of immune checkpoint inhibitors efficiency, as well as the origins of treatment failure, require further investigation. From a clinical standpoint, discrepancies between the theoretical explanation of inhibitors of immune checkpoint actions at the cellular level and their deployment at a tissue/organ level impede the effective clinical implementation of novel immune therapy. The present review assessed existing experimental and clinical data on functional activity of inhibitors of immune checkpoints to provide a more comprehensive picture of their mechanisms of action on a cellular and higher levels of biological organization.     

Osimertinib successfully combats EGFR-negative glioblastoma cells by inhibiting the MAPK pathway

Glioblastoma(GBM)patients have extremely poor prognoses,and currently no effective treatment available including surgery,radiation,and chemotherapy.MAPK-interacting kinases(MNK1/2)as the downstream of the MAPK-signaling pathway regulate protein synthesis in normal and tumor cells.Research has shown that targeting MNKs may be an effective strategy to treat GBM.In this study we investigated the antitumor activity of osimertinib,an FDA-approved epidermal growth factor receptor(EGFR)inhibitor,against patient-derived primary GBM cells.Using high-throughput screening approach,we screened the entire panel of FDA-approved drugs against primary cancer cells derived from glioblastoma patients,found that osimertinib(3μM)suppressed the proliferation of a subset(10/22)of EGFR-negative GBM cells(>50%growth inhibition).We detected the gene expression difference between osimertinib-sensitive and-resistant cells,found that osimertinib-sensitive GBM cells displayed activated MAPK-signaling pathway.We further showed that osimertinib potently inhibited the MNK kinase activities with IC50 values of 324 nM and 48.6 nM,respectively,against MNK1 and MNK2 kinases;osimertinib(0.3–3μM)dose-dependently suppressed the phosphorylation of eukaryotic translation initiation factor 4E(eIF4E).In GBM patient-derived xenografts mice,oral administration of osimertinib(40 mg·kg^?1·d^?1,for 18 days)significantly suppressed the tumor growth(TGI=74.5%)and inhibited eIF4E phosphorylation in tumor cells.Given the fact that osimertinib could cross the blood–brain barrier and its toxicity was well tolerated in patients,our results suggest that osimertinib could be a new and effective drug candidate for the EGFR-negative GBM patients.     

Effect of chinese medicine therapy for strengthening-Pi and nourishing-shen in preventing lamivudine induced YMDD mutation and its immunologic mechanism

<正>Objective:To observe the effect of Chinese medicine therapy for strengthening-Pi(脾) and nourishing-Shen(肾,SPNS) in preventing lamivudine induced YMDD mutation and its immunological mechanism.Methods:One hundred and sixty chronic hepatitis B(CHB) patients with positive HBeAg were equally assigned to two groups at random:the observation group and the control group.Patients in the observation group were treated with lamivudine combined with SPNS,and those in the control group were treated with lamivudine only,with the treatment lasting for 52 weeks in total.Changes in indexes,including liver function,HbeAg,HBV-DNA,YMDD variation,CD_4,CD_4/CD_8 ratio,interferon-γ(IFN-γ),interleukin-4(IL-4), blood routine,renal function,as well as any adverse reactions that occurred in patients,were observed at different time points.Results:The ALT,AST recovery rate and HBV-DNA negatively inversing rate at the 24th week,the 36th week and the 52nd week were all higher(P0.05);meanwhile,the YMDD mutation rate at the 36th week and the 52nd week was lower(P0.05) in the observation group than in the control group.The posttreatment levels of CD_4,CD_4/CD_8 ratio,IFN-γ,and IL-4 as well as the pre-post treatment difference of these indexes in the observation group were significantly different from those in the control group(P0.05).Conclusion: Chinese medicine SPNS therapy can significantly reduce the YMDD variation of HBV,and the mechanism may be related to its regulation of the CD_4 level,CD_4/CD_8 ratio and Th1/Th2 balance.     

基于抗耐药性细菌感染的抗菌肽研究进展

随着抗生素的发现及滥用,耐药细菌感染已威胁到了人们的健康,现有抗生素已不能满足临床治疗的需求。因此,解决这一问题已迫在眉睫。本文针对耐药细菌的耐药机制及抗菌肽(antimicrobial peptides,AMPs)这一新型广谱抗菌药物的研究进展进行了综述。     

清热解毒复方对头孢拉定的抑菌增效作用及机理

目的 研究清热解毒中药复方对头孢拉定的体外抑菌增效作用及其机制.方法 采用棋盘法观察中药复方与头孢拉定联用对金黄色葡萄球菌的抑菌作用;利用生物大分子分析、糖代谢、AKP的含量测定等方法,来验证清热解毒中药复方的药效作用.结果 清热解毒中药复方与头孢拉定两药联用对金黄色葡萄球菌的抑菌浓度指数(FIC)为0.125;中药复方作用金黄色葡萄球菌后,DNA和RNA的含量比正常组仅增加0.47%,糖浓度仅增加5.47%,AKP含量比正常组增加484.7%;菌体可溶性蛋白表达与正常组相比有明显变化.结论 清热解毒中药复方对头孢拉定有协同抑菌作用,其机理与增加细胞壁透性、影响蛋白质表达有关.     

On Growth and Morphology of TiO2 Nanotubes on CP-Ti by Anodic Oxidation in Ethylene Glycol Electrolyte: Influence of Electrolyte Aging and Anodization Parameters

Anodic oxidation of CP-Ti, for production of TiO₂ nanotubes, has been extensively described in terms of the electrochemical mechanism of tubular growth or the effect of the parameters on the final tube morphology. Recently, a kinetic growth model was proposed to describe the distinct morphologies of the anodic oxide layer as phases of the nanotubular development process, offering a new perspective for the tuning of nanotube production. In this work, the anodizing behavior of a CP-Ti alloy in an ethylene glycol electrolyte was investigated in light of this new model. The final morphology of the nanotubes was characterized by SEM, considering the effects of electrolyte aging, the microstructure, the applied potential difference and time on the morphological development of nanotubes. Electrolyte aging was shown to lead to a decreased dissolution effect on the oxide. The applied potential difference was shown to lead to an increased dissolution effect and more rapid nanotube growth kinetics, while time resulted in extended dissolution. Moreover, the obtained results were analyzed considering a previous study focused on the anodizing behavior of the α- and β-phases of Ti6Al4V alloy. Overall, the tube morphology resembled that obtained for the Al-containing α-phase of the Ti6Al4V alloy, but the growth kinetics were considerably slower on CP-Ti.     

噪声性耳聋致病机制的研究进展

噪声性耳聋是由于听觉长时间遭受噪声作用或因耳疲劳引起的缓慢渐进性的感音性耳聋,早期表现为听觉疲劳,离开噪声环境后可以逐渐恢复,久之则难以恢复,最终形成感音神经性聋。因此,减少或消灭噪声为当今环境保护工作中的一项重要内容。了解因噪声导致内耳、听神经等发生病变的具体机制并加深对组织结构的了解在正确引导噪声性耳聋的筛查和防治工作中起到了重要的作用。     

脑小血管疾病病理机制的研究进展

在过去十年中全球预期寿命大幅增加,与年龄相关性疾病对社会和卫生保健系统造成的挑战愈演愈烈.脑小血管疾病(cerebral small vessel disease,CSVD)是一种增龄性脑微血管病变,其患病率随年龄增长而增加,在50～90岁人群中患病率由5％升至几乎100％,是导致卒中和血管性痴呆的重要血管因素,并与步...