常见植物药对结肠癌的防治作用及其作用机制

植物药对结肠癌具有良好的防治作用。姜黄素、多糖(苹果多糖、香菇多糖)、皂苷(重楼皂苷、人参皂苷)、白藜芦醇、槲皮素等植物药可通过不同信号通路抑制结肠癌细胞的增殖,促进细胞凋亡。此外,植物药还具有抗炎、抗氧化、抗血管生成、减轻化疗药物不良反应、逆转肿瘤细胞耐药等作用。了解植物药对结肠癌的防治作用及其可能的作用机制,能为结肠癌的临床防治提供更多的理论依据及治疗思路。     

中药糖肾方单体成分莫诺苷药理作用的研究进展

通过查阅近些年的国内外文献对中药糖肾方单体成分莫诺苷的药理作用及分子机制进行归纳、梳理、分析及总结。从分子机制角度阐述莫诺苷具有促进细胞生长、减轻炎性反应、抑制细胞内钙超载、抑制氧化应激、抗凋亡、抗凝等作用,以便为今后临床及实验研究提供更多科学依据。     

赤芍的抑菌作用及其防治慢性牙周炎的机制研究

目的 研究赤芍提取物对牙龈卟啉单胞菌（Porphyromonas gingivalis，P.g）、具核梭杆菌（Fusobacterium nucleatum，F.n）和伴放线聚集杆菌（Actinobacillus Actinomycetes，A.a）的抑菌作用，并通过网络药理学方法分析赤芍防治慢性牙周炎（chronic periodontitis，CP）的潜在分子机制和药理活性。方法 采用倍比稀释法测定赤芍提取物对3种牙周致病菌（P.g、F.n、A.a）的最低抑菌浓度（minimum inhibitory concentration，MIC）及最低杀菌浓度（minimal bactericidal concentration，MBC）。借助TCMSP数据库获取赤芍化学成分及作用靶点，通过Genecards等数据库获取CP疾病靶点，韦恩分析取交集。利用Cytoscape 3.7.2软件构建赤芍防治CP的“成分-靶点-疾病”网络，采用STRING数据库构建蛋白互作网络（Protein protein interaction network，PPI network），并进行基因本体（Gene Ontology，GO）和京都基因和基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）富集分析。结果 赤芍提取物对P.g、F.n、A.a的MIC分别为2.0、4.0、4.0 g/L，MBC分别为4.0、8.0、8.0 g/L。分析获得赤芍活性成分29个，CP疾病靶点2 132个，交集靶点89个。赤芍治疗CP的主要活性成分有黄芩苷、鞣花酸等，关键靶点包括白细胞介素-6（Interleukin-6，IL-6）等。GO富集分析得到蛋白质异构化活性等126个GO条目，KEGG富集分析得到丝裂原活化蛋白激酶（Mitogen-activated protein kinase，MAPK）等110条通路。结论 赤芍提取物对3种牙周致病菌均有不同程度的抑菌作用，初步阐述了赤芍的主要成分、作用靶点和相关通路在防治CP中具有重要的研究价值，为进一步深入临床研究提供实验依据和理论支持。     

骨碎补化学成分和生物活性研究进展＊

骨碎补是历代临床常用中药，具有疗伤止痛、补肾强骨、消风祛斑等功效。其主要含黄酮、苯丙素、三萜、酚酸及其苷等类化学成分，现代研究表明骨碎补具有抗骨质疏松、促进骨折愈合、促软骨再生、护牙健齿、保护肾功能、抗炎、防治中毒性耳聋、降血脂等多种生物活性，开发前景广阔。本文对近年来骨碎补的化学成分、药理作用及临床应用研究进行综述，以期为骨碎补的进一步深入系统的研究和开发利用提供依据。     

基于网络药理学和分子对接探讨钩藤-全蝎药对治疗支气管哮喘的作用机制＊

目的通过网络药理学和分子对接探究钩藤-全蝎药对治疗支气管哮喘的药理作用机制。方法通过TCMSP、TCMIP数据库搜集钩藤、全蝎的活性成分及其作用靶点,并使用Cytoscape软件进行可视化分析成分-靶点网。通过OMIM、GeneCards数据库搜集支气管哮喘的疾病靶点,整合钩藤-全蝎药对与支气管哮喘的共有靶点。利用String平台构建对共有靶点互作PPI网络,并进行GO和KEGG富集分析,通过Cytoscape软件构建成分-靶点-通路网络模型。最后通过Autodock分子对接进行验证。结果经过筛选发现钩藤-全蝎药对37个活性化合物和234个药物靶点,与哮喘6010个靶点取交集得到35个共有靶点。钩藤-全蝎包含槲皮素、山奈酚、育亨宾碱、β-谷甾醇等重要活性成分;根据PPI网络分析,核心网络连接度高的潜在治疗靶点有IL6、CASP3、ECFR、ESR1、MAPK8等;根据KEGG富集分析结果显示,钩藤-全蝎药对主要通过PI3 K-Akt信号通路、TNF信号通路,HIF-1信号通路、M APK信号通路、NF-κB信号通路等来治疗哮喘;钩藤-全蝎药对活性成分与核心靶点的分子对接结果均显示出较好的结合活性。结论钩藤-全蝎药对治疗哮喘呈现出多成分、多靶点、多通路的特点,其核心成分槲皮素、山奈酚、育亨宾碱、β-谷甾醇等可能通过CASP3、MAPK8、ESR1、IL6、ECFR等靶点调节多条通路发挥抗炎、调节免疫、抗氧化应激、改善气道重塑等作用,从而对哮喘达到有效的治疗。     

Intraoperative lateral rectus electromyographic recordings optimized by deep intraorbital needle electrodes

ObjectiveWe demonstrate the advantages and safety of long, intraorbitally-placed needle electrodes, compared to standard-length subdermal electrodes, when recording lateral rectus electromyography (EMG) during intracranial surgeries.MethodsInsulated 25 mm and uninsulated 13 mm needle electrodes, aimed at the lateral rectus muscle, were placed in parallel during 10 intracranial surgeries, examining spontaneous and stimulation-induced EMG activities. Postoperative complications in these patients were reviewed, alongside additional patients who underwent long electrode placement in the lateral rectus.ResultsIn 40 stimulation-induced recordings from 10 patients, the 25 mm electrodes recorded 6- to 26-fold greater amplitude EMG waveforms than the 13 mm electrodes. The 13 mm electrodes detected greater unwanted volume conduction upon facial nerve stimulation, typically exceeding the amplitude of abducens nerve stimulation. Except for one case with lateral canthus ecchymosis, no clinical or radiographic complications occurred in 36 patients (41 lateral rectus muscles) following needle placement.ConclusionsIntramuscular recordings from long electrode in the lateral rectus offers more reliable EMG monitoring than 13 mm needles, with excellent discrimination between abducens and facial nerve stimulations, and without significant complications from needle placement.SignificanceLong intramuscular electrode within the orbit for lateral rectus EMG recording is practical and reliable for abducens nerve monitoring.     

Review of the pharmacological effects of astragaloside IV and its autophagic mechanism in association with inflammation

Astragalus membranaceus Bunge, known as Huangqi, has been used to treat various diseases for a long time. Astragaloside IV (AS-IV) is one of the primary active ingredients of the aqueous Huangqi extract. Many experimental models have shown that AS-IV exerts broad beneficial effects on cardiovascular disease, nervous system diseases, lung disease, diabetes, organ injury, kidney disease, and gynaecological diseases. This review demonstrates and summarizes the structure, solubility, pharmacokinetics, toxicity, pharmacological effects, and autophagic mechanism of AS-IV. The autophagic effects are associated with multiple signalling pathways in experimental models, including the PI3KI/Akt/mTOR, PI3K III/Beclin-1/Bcl-2, PI3K/Akt, AMPK/mTOR, PI3K/Akt/mTOR, SIRT1–NF-κB, PI3K/AKT/AS160, and TGF-β/Smad signalling pathways. Based on this evidence, AS-IV could be used as a replacement therapy for treating the multiple diseases referenced above.     

Activation of voltage‐gated sodium current and inhibition of erg‐mediated potassium current caused by telmisartan,an antagonist of angiotensin II type‐1 receptor,in HL‐1 atrial cardiomyocytes

Telmisartan (TEL) is a non‐peptide blocker of angiotensin II type‐1 (AT₁) receptor. However, the mechanisms through which this drug interacts directly with ion currents in hearts remain largely unclear. Herein, we aim to investigate the effects of TEL the on ionic currents and membrane potential of murine HL‐1 cardiomyocytes. In whole‐cell recordings, addition of TEL stimulated the peak and late components of voltage‐gated Na⁺ currents (I_Na) with different potencies. The EC₅₀ values required to achieve the stimulatory effect of this drug on peak and late I_Na were 0.2 and 1.2 μmol/L, respectively, and the current‐voltage relationship of peak I_Na shifted toward less‐depolarized potentials during exposure to TEL. Telmisartan not only increased peak I_Na but also prolonged the inactivation time course of late I_Na. Amiodarone (Amio) or ranolazine (Ran), but not angiotensin II, could reverse TEL‐mediated effects. The drug enhanced the recovery rate of I_Na inactivation and exerted an inhibitory effect on erg‐mediated K⁺ and L‐type Ca²⁺ currents. In whole‐cell current‐clamp recordings, addition of the drug resulted in prolongation of the duration of action potentials (APs) in a dose‐dependent manner in HL‐1 cells; Amio or Ran could reverse this increase in AP durations. Telmisartan‐mediated prolongation of AP was attenuated in KCNH2 siRNA‐transfected HL‐1 cells. In cultured smooth muscle cells of the human coronary artery, TEL enhanced I_Na amplitudes and slowed current inactivation. Stimulation by TEL of I_Na in HL‐1 cells did not simply increase current magnitude but altered current kinetics, thereby suggesting state‐dependent activation. Telmisartan may have greater affinity to the open/inactivated state than to the resting state residing in Na_V channels. Collectively, TEL‐mediated stimulation of I_Na and inhibition of I_K(erg) could be an important ionic mechanism underlying the increased cell excitability of HL‐1 cells; these actions, however, cannot be entirely explained by its blockade of AT₁ receptor.