Diabetes as a risk factor for periodontal disease—plausible mechanisms

The present narrative review examines the scientific evidence of the biological mechanisms that may link periodontitis and diabetes, as a source of comorbidity. Publications regarding periodontitis and diabetes, in human, animals, and in vitro were screened for their relevance. Periodontal microbiome studies indicate a possible association between altered glucose metabolism in prediabetes and diabetes and changes in the periodontal microbiome. Coinciding with this, hyperglycemia enhances expression of pathogen receptors, which enhance host response to the dysbiotic microbiome. Hyperglycemia also promotes pro-inflammatory response independently or via the advanced glycation end product/receptor for advanced glycation end product pathway. These processes excite cellular tissue destruction functions, which further enhance pro-inflammatory cytokines expression and alteration in the RANKL/osteoprotegerin ratio, promoting formation and activation of osteoclasts. The evidence supports the role of several pathogenic mechanisms in the path of true causal comorbidity between poorly controlled diabetes and periodontitis. However, further research is needed to better understand these mechanisms and to explore other mechanisms.     

中医药调控IL-1治疗肿瘤机制的研究进展

炎症已成为影响肿瘤细胞增殖转移的第七大因素,而白细胞介素-1(IL-1)是炎性微环境的重要因子之一。中医药在治疗肿瘤时具有多途径、多靶点的优势,同时炎性微环境致病特点与现代中医学"癌毒"的理论相吻合。查阅近年中医药调控IL-1家族分子治疗肿瘤机制的文献,对其进行梳理,并做出概括及评价,从中医药主要调控IL-1α、IL-1β和IL-18因子治疗肿瘤展开综述,为中医药更系统化治疗肿瘤提供参考。     

Colorectal serrated pathway cancers and precursors

The serrated pathway (SP) can be viewed as two parallel, but partially overlapping, arrays of colorectal precursor lesions, and their respective endpoint carcinomas, that are distinct from those of the conventional adenoma–carcinoma sequence (APC‐pathway). In this review we focus at the outset on the clinical impact, pathological features, molecular genetics and biological behaviours of the various SP cancers. Then we summarize the clinicopathological features, classification and molecular profiles of the two main precursor lesions that anchor the respective pathways: (i) sessile serrated adenoma/polyp (SSA/P), also called sessile serrated lesion (SSL), and (ii) traditional serrated adenoma (TSA). Activating mutations of the RAS–RAF–MAPK pathway initiate and sustain the lesions of the SP, and CpG island methylation of the promoter regions of tumour suppressor and DNA repair genes play the major role in their neoplastic progression. The SP includes microsatellite stable (MSS) carcinomas that are among the most biologically aggressive colorectal carcinomas (CRC), and also accounts for the great preponderance of sporadic hypermutated, mismatch repair (MMR)‐deficient or microsatellite instable (MSI) CRC. The identification, removal and appropriate classification of at‐risk SP precursors and surveillance of individuals who harbour these lesions present a challenge and opportunity for CRC prevention and mortality reduction.     

Reactivation of heat-inactivated Ku proteins by heat shock cognate protein HSC73

Purpose: Mouse double-stranded DNA-dependent protein kinase (DNA-PK) activity is heat sensitive. Recovery of heat-inactivated DNA repair activity is a problem after combination therapy with radiation and heat. We investigated the mechanism of recovery of heat-inactivated DNA-PK activity.

Methods: Hybrid cells containing a fragment of human chromosome 8 in scid cells (RD13B2) were used. DNA-PK activity was measured by an in vitro assay. Immunoprecipitation of the nuclear extract was performed with an anti-Ku80 antibody. Proteins co-precipitated with Ku80 were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and detected by Western blotting using anti-heat shock protein (HSP)72 and anti-heat shock cognate protein (HSC)73 antibodies. HSC73 was overexpressed with the pcDNA3.1 vector. Short hairpin (sh)RNA was used to downregulate HSC73 and HSP72.

Results: The activity of heat-inactivated DNA-PK recovered to about 50% of control during an additional incubation at 37?°C after heat treatment at 44?°C for 15?min in the presence of cycloheximide (which inhibits de novo protein synthesis). Maximal recovery was observed within 3?h of incubation at 37?°C after heat treatment. Constitutively expressed HSC73, which folds newly synthesized proteins, reached maximal levels 3?h after heat treatment using a co-immunoprecipitation assay with the Ku80 protein. Inhibiting HSC73, but not HSP72, expression with shRNA decreased the recovery of DNA-PK activity after heat treatment.

Conclusions: These results suggest that de novo protein synthesis is unnecessary for recovery of some heat-inactivated DNA-PK. Rather, it might be reactivated by the molecular chaperone activity of HSC73, but not HSP72.     

藿香正气汤抑制新型冠状病毒复制过程的有效成分及机制初探＊

目的 收集藿香正气汤的主要活性成分，通过分子对接及网络药理学探讨其防控新型冠状病毒肺炎（COVID-19）的有效成分及治疗机制。方法 通过基于配体-蛋白质相互作用的计算方法，以瑞德西韦为对照，探索藿香正气汤潜在治疗COVID-19的成分，并选出对接较好成分进行药理学机制预测，初探其药理学机制。结果 本研究筛选出5种与新冠病毒3CLpro结合能力强于瑞德西韦的小分子成分。网络药理学初步预测抗病毒途径可能是通过PI3K-Akt 信号通路影响病毒复制。结论 成分C1-C5与3CLpro结合良好，推测其可能是潜在的3CLpro的抑制剂，为抗病毒天然药物的开发提供了理论依据。     

冠状病毒感染对心血管系统的损伤及可能机制

冠状病毒(coronavirus,CoVs)感染主要累及肺部,但对心血管系统损伤作用也不容忽视。CoVs感染引起的心脏损伤并非罕见,其发生与病情的严重程度密切相关。本文首先从CoVs引起心血管损伤的证据入手,进一步探讨了CoVs对心肌的直接损伤,以及肾素血管紧张素(RAS)系统激活和细胞因子风暴与炎症反应对心血管损伤的可能作用机制。相关心血管损伤的可能机制包括,(1)病毒直接作用:CoVs在心肌细胞复制,损伤心肌;(2)RAS系统激活:感染CoVs后,心脏血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)的表达下调,激活RAS系统,使得血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)收缩血管功能增强,Ang1-7保护心脏效应减弱;(3)诱发细胞因子风暴:循环细胞因子和全身炎症反应引起心脏损伤;(4)其他:包括低氧血症和儿茶酚胺心脏毒性。本文就相关内容作一综述,为后续的详尽机制和治疗策略研究提供思路。     

早发型子痫前期应用低分子肝素期待治疗的临床效果分析

目的分析早发型子痫前期应用低分子肝素期待治疗的临床效果。方法回顾分析2017-01—2018-12间在郑州大学第一附属医院产科终止妊娠的95例早发型子痫前期患者的临床资料。按终止妊娠前是否应用低分子肝素分为2组。对照组(47例)给予降压、解痉等治疗;观察组(48例)在对照组基础上加用低分子肝素。结果2组分娩孕周、妊娠延长时间、妊娠并发症发生率、新生儿出生体质量、新生儿窒息及胎儿宫内窘迫发生率、新生儿Apgar评分等,差异均无统计学意义(P>0.05)。结论对早发型子痫前期患者在常规治疗基础上短期应用低分子肝素,不能延长妊娠时间,不改善母婴结局。