Expression of brain-derived neurotrophic factor in rapid ejaculator rats: A further study

Limited evidence has indicated that brain-derived neurotrophic factor (BDNF) may be involved in the neurobiology of premature ejaculation (PE). This study aimed to investigate BDNF levels in the central and peripheral nervous systems of a rapid ejaculation model. Eighteen male rats were selected and classified as ‘sluggish’, ‘normal’ and ‘rapid’ ejaculators on the basis of ejaculation frequency during copulatory behavioural tests. BDNF levels in specific brain regions, spinal cord and serum were determined by enzyme-linked immunosorbent assay (ELISA). Consistent with the results in PE patients, the concentration of serum BDNF decreased significantly from the sluggish rats to normal and rapid rats. Besides, in both brain regions and spinal cord, the sluggish group had the highest BDNF levels, while the rapid group had the lowest BDNF levels. Regression analyses of the expression of BDNF presented positive correlations between serum and brain (r = 0.958, p < .001), and between serum and spinal cord (r = 0.967, p < .001) respectively. Our findings suggested insufficient BDNF in the nervous system and serum may lead to rapid ejaculation. The current study adds to the evidence that BDNF is involved in the regulation of ejaculation.     

Activation of Nrf2 Pathway by Dimethyl Fumarate Attenuates Renal Ischemia-Reperfusion Injury

BackgroundDimethyl fumarate (DMF) is a novel antioxidant that selectively reduces hydroxyl radicals. This study aimed to investigate the potential role of DMF in the pathogenesis of renal ischemia-reperfusion injury (IRI) and the mechanisms involved.MethodsC57BL/6 wild-type mice were treated with DMF or a vehicle. Subsequently, renal IRI was induced in mice by a model of right kidney nephrectomy and left renal ischemia for 30 minutes followed by reperfusion for 24 hours. Sham operation and phosphate-buffered saline were used as controls. Serum and renal tissues were collected at 24 hours after IRI to evaluate the influence of DMF on the recovery of renal function after IRI. Blood urea nitrogen and serum creatinine levels were measured. Kidney cell apoptosis was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling-positive staining. Interleukin 6 and tumor necrosis factor α cytokines in the kidney tissues were measured. Indicators of oxidative stress in the kidneys were detected. Finally, Nrf2-deficient mice were used to determine the protective role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) signaling pathways induced by DMF using western blot assay.ResultsDMF significantly attenuated renal dysfunction in mice and showed reductions in the severity of renal tubular injury, cell necrosis, and apoptosis. Moreover, DMF significantly reduced the amount of key inflammatory mediators. Additionally, DMF attenuated the malondialdehyde levels 24 hours after IRI but upregulated the superoxide dismutase activities. Western blot assay showed that DMF significantly increased the protein levels of Nrf2, HO-1, and NQO-1. Importantly, these DMF-mediated beneficial effects were not observed in Nrf2-deficient mice.ConclusionsDMF attenuates renal IRI by reducing inflammation and upregulating the antioxidant capacity, which may be through Nrf2/HO-1and NQO1 signaling pathway.     

Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma

ObjectiveAlthough there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown.MethodsSmall interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2′-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting.ResultsJAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML.ConclusionJAML is a novel target for kaempferol against LUAD cells.Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268–276.     

Ferulic acid enhances insulin secretion by potentiating L-type Ca2+ channel activation

ObjectiveTo investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca²⁺ channels, and insulin secretion.MethodsWe studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca²⁺ channels and insulin secretion, respectively.ResultsFerulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca²⁺ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca²⁺ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca²⁺-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca²⁺ influx through L-type Ca²⁺ channel. Our data also suggest that this may be a direct, nongenomic action.ConclusionThis is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca²⁺ channel current in pancreatic β cells by enhancing its voltage dependence of activation, leading to insulin secretion.     

Scientific connotation of “treating different diseases with the same method” from the perspective of metabolic–immune dysregulation in inflammation-mediated carcinogenesis of digestive organs

Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system. In the chronic inflammation microenvironment, the metabolic activity of tissue cells undergoes extensive changes, which interfere with the normal function of immune cells. Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs, such as the stomach, liver, and colorectum. This metabolic–immune imbalance also corresponds to traditional Chinese medicine (TCM) theories of “yin-yang disharmony” and “disharmony between Ying-nutrients and Wei-defense.” The metabolic–immune imbalance has also been regarded as the key factor supporting “treatment of different diseases with the same method,” in which the same approach is adopted in the treatment of different conditions. In the TCM treatment process, it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function, thereby blocking the progression from inflammation to malignancy. Our study findings deepen the TCM understanding of metabolic–immune dysregulation and the relationship between metabolic–immune dysregulation, pattern identification, and treatment method. They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of “treating different diseases with the same method.     

基于“药辅合一”理念的Pickering乳技术提升儿科用药羚珠散中石菖蒲挥发油热稳定性的研究

目的 在“药辅合一”理念下导入Pickering乳技术,提升儿科用药羚珠散中石菖蒲挥发油的稳定性。方法 对羚珠散各饮片粉末进行初步表征,确定稳定剂。通过成乳量、包油量和乳剂形态筛选出最佳稳定剂质量浓度、油水比和制备方法。并使用近红外光谱（nearinfraredspectroscopy,NIRS）分析石菖蒲油在Pickering乳中的包裹状态。比较不同时间下各组别挥发油的保有量、丙二醛和过氧化物的含量。再通过GC-MS分析其中成分的变化趋势。结果 筛选出珍珠粉作为Pickering乳的稳定剂,珍珠粉质量浓度为65 mg/mL,油水比9∶11为最优成乳条件,高压均质法为最优的制备方法,NIRS分析可知石菖蒲挥发油被珍珠粉包裹,Pickering乳液中没有形成新的化学键。对比各组在不同时间段下石菖蒲油的保有率和其中丙二醛和过氧化物含量,可知40℃放置1、3、8 h的Pickering乳剂相比于石菖蒲挥发油组有更高的保有率和更低的氧化程度。GC-MS分析结果表明,相比于石菖蒲挥发油组,Pickering乳组挥发性成分的稳定性显著提高。结论 在“药辅合一”理念下Pickering乳可用于含油固...     

《伤寒论》治疫方用药规律分析及核心药对治疗COVID-19的作用机制研究

目的 基于数据挖掘分析《伤寒论》疫病治疗相关方剂的用药规律,并利用网络药理学分析核心药对“柴胡-黄芩”治疗新型冠状病毒肺炎（coronavirus disease 2019,COVID-19）的作用机制。以期探讨经方治疗疫病的当代价值。方法 筛选《伤寒论》中治疗疫病的经方,利用R语言等软件对频次、性味归经、相关性、关联规则等用药规律进行分析,并运用网络药理学方法对用药规律中核心药对治疗COVID-19的机制进行探究。用Cytoscape对筛选出的成分及靶点构建“疾病-药物-成分-靶点”网络,将关键靶点导入String数据库进行蛋白相互作用（protein-protein interaction,PPI）网络分析,并在R语言中进行基因本体论（gene ontology,GO）功能分析和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路分析。结果 纳入《伤寒论》中与疫病相关的方剂61首,共52味中药。前20味高频用药中以温性药、辛味药为主,多归脾、肺经,功效以补气药居多。“柴胡-黄芩”药对相关性最强,5个类聚方为小柴胡汤...     

黄芪和蜜炙黄芪中糖类组分和非糖类组分的差异性研究

目的 比较研究黄芪蜜炙后多糖、单糖、寡糖及非糖类小分子成分的整体变化。方法 结合糖组学和代谢组学,运用超高效液相-二极管阵列检测器(ultra high performance liquid-photodiode array detector,UPLC-PDA)、高效液相-蒸发光散射检测器(ultra high performance liquid-evaporative light scattering detector,HPLC-ELSD)、高效凝胶渗透色谱-蒸发光散射检测器(high performance gel permeation chromatography-evaporative light scattering detector,HPGPC-ELSD)和超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(ultra high performance liquid chromatography-quadrupole/electrostatic field orbit-trap high resolution mass spectrometr,UHPLC-Q-Orbitrap...     

面向行业需求的中医药标准：发展现状与建设思考

在科学技术蓬勃发展的现代社会,标准建设在各行各业的必要性和重要性不断彰显,中医药标准建设则是推进中医药事业发展、促进中医药更好服务于人类健康的关键所在。伴随着国家政策支持及更多研究人员的关注,中医药标准建设工作已取得显著成效。紧跟标准改革的步伐,同时面向行业的需求,梳理了当前中医药行业标准研究与制定的概况,解析新时期下标准建设所面临的机遇与挑战及其不足,旨在为中医药标准引领行业高质量发展提供参考。