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.     

Anticonvulsant efficacy of antihistamine cyproheptadine in rats exposed to the chemical warfare nerve agent soman

Organophosphate compounds, such as soman and sarin, are highly toxic chemical warfare nerve agents that cause a build-up of acetylcholine in synapses and neuromuscular junctions. Current therapies aim to prevent seizures and protect against brain injury following exposure. The present study was designed to evaluate the effectiveness of the antihistamine cyproheptadine in improving survival and controlling seizures in rats exposed to soman. Rats were pretreated with the oxime reactivator HI-6 (125 mg/kg, ip) 30 min prior to soman exposure (225 μg/kg, sc) and then treated with atropine methylnitrate (AMN, 2.0 mg/kg, im) 1 min after soman. Cyproheptadine (10, 13, 16 or 20 mg/kg, ip) was given at one of three time points: 1 min after soman intoxication, at the onset of soman-induced seizures or 5 min after seizure onset. Control animals were exposed to soman and given an equivalent volume of sterile water instead of cyproheptadine. The incidence of seizures, mortality, neuron counts, neuropathology and apoptosis in specific regions of the brain were evaluated. In animals given HI-6 and AMN the incidence of soman-induced seizure and mortality rate within the first 24 h were 100%. When cyproheptadine was given at a dose of 13 or 20 mg/kg 1 min after soman exposure, the incidence of seizures was reduced from 100% to 13% and 30%, respectively. In addition, cyproheptadine given at 1 min after soman exposure increased the survival rate to 100% regardless of dose. When cyproheptadine was administered at seizure onset, seizures were terminated in 100% of the animals at doses above 10 mg/kg. The survival rate with cyproheptadine treatment at the onset of seizure was ≥83%. Seizures terminated in ≥75% of the animals that received cyproheptadine 5 min after soman-induced seizure onset. When given at 5 min after seizure onset the survival rate was 100% at all tested doses of cyproheptadine. The neuropathology scores and the number of TUNEL positive cells in the brain regions examined decreased at all time points and cyproheptadine doses tested. These observations indicate that cyproheptadine treatment can effectively control seizures, improve survival, reduce seizure duration and reduce the number of dying cells in the brain following soman exposure.     

一起“挪威疥疮”医院内暴发与处置

目的调查某院一起疥疮医院感染暴发的原因和处置方法。方法 2013年5月该院因1例"挪威疥疮"患者误诊,引起医务人员疥疮医院感染暴发,该院医院感染控制科对暴发事件进行流行病学调查,并根据调查结果指导医疗及消毒隔离。结果医务人员及其家属,共计27人感染挪威疥疮。经积极药物治疗,患者病情逐渐好转;患者使用过的物品全部用塑料口袋包装密封1周后进行清洗消毒。经积极治疗加严格清洗消毒后,感染流行趋势得到控制,未再出现新发病例。结论挪威疥疮传染性高,可在局部地区造成流行,需提高医务人员对本病的诊断能力;一旦发生医院感染,应采取快速、有效措施,防止其蔓延、扩散。     

Non-invasive assessment of cerebrospinal fluid flow dynamics using phase-contrast magnetic resonance imaging in communicating hydrocephalus

This work aims to evaluate the changes in cerebrospinal fluid (CSF) hydrodynamics in patients diagnosed with communicating hydrocephalus. Besides, we establish the relationship between CSF flow dynamic parameters on the midbrain aqueduct and intracranial pressure (ICP). CSF hydrodynamics analysis was performed using Phase-Contrast Magnetic Resonance Imaging (PC‐MRI) techniques on the midbrain aqueduct of 41 patients diagnosed with communicating hydrocephalus and 22 healthy volunteers. The correlation between CSF average flow in the midbrain aqueduct and intracranial pressure measured by Lumbar Puncture (LP) was assessed in patients with hydrocephalus. Pearson correlation coefficient was used to establish the correction between the average CSF flow of midbrain aqueduct and ICP. CSF dynamic parameters of the midbrain aqueduct in hydrocephalus patients, including peak positive velocity (7.348 cm/s), average velocity (0.623 cm/s), average flow (50.799 mm³/s), and regions of interest (ROI) area (9.978 mm²) were significantly higher than in the healthy controls (p < 0.05). This was after adjusting the age, gender, heart rate, systolic blood pressure, diastolic blood pressure, and body mass index. However, only the peak negative velocity of the midbrain aqueduct did not significantly differ between the groups (p = 0.209). A positive correlation was noted between the average flow (AF) of the midbrain aqueducts and ICP in hydrocephalus patients (y (AF) = 0.386× (ICP)−33.738, r = 0.787, p < 0.05). Reference data of CSF flow dynamic parameters was obtained through the PC-MRI in middle-aged healthy volunteers and communicating hydrocephalus patients. Although the sample size was constrained, this study has significant contributions. For instance, a significant correlation was noted between the average CSF flow of the aqueduct and ICP. This therefore provides a reference for clinicians to monitor ICP in patients with hydrocephalus.     

藤梨根提取物对大肠癌LoVo细胞增殖的抑制作用及诱导凋亡的影响

目的:研究藤梨根提取物(ethanol extract from radix of actinidia chinensis,EERAC)对人大肠癌LoVo细胞增殖和凋亡的影响.方法:提取藤梨根抗癌有效活性成分(EERAC),按浓度分为4处理组(10、40、160、320mg/L)和空白对照组(0mg/L).各实验组经作用24、48、72h后,进行一般形态学和AO/EB荧光染色观察;MMT法检测细胞增殖的抑制情况;免疫组织化学(immunohistochemistry,IHC)法测定LoVo细胞中凋亡相关基因Bcl-2、Bax、Caspase-3的蛋白表达变化.结果:与空白对照组比较,一般形态学显示EERAC处理组能使细胞密度减低,增殖变慢;细胞逐渐变大,细胞间接触变松,胞浆中颗粒增多,细胞脱壁现象和周围碎片增多;荧光染色观察可见处理组细胞呈橙红色荧光,细胞核出现碎片状或固缩状的凋亡特征学形态改变,凋亡现象与EERAC的浓度呈正相关性;MTT法检测显示,EERAC处理组对LoVo细胞的最佳作用时间为72h,最大抑制率为79.48%,具有浓度和时间的依赖性(P<0.01);IHC检测结果显示EERAC作用LoVo细胞24h后,Bcl-2表达明显减弱,Bax、Caspase-3表达水平明显增高,Bcl-2/Bax比值下降,差异具有统计学意义(P<0.05),其效应与浓度相关.结论:EERAC具有明显抑制LoVo细胞增殖的作用,其机制可能与降低Bcl-2表达,上调Bax、Caspase-3的表达水平,激活线粒体凋亡途径有关.     

骨质疏松症“病本在脾，以阴阳两虚为要”之见探讨

骨质疏松症素以肾虚为本,临床以补肾益精、滋肾养阴等治为要,然时效时逊。脾胃是为后天之本,不仅充养先天之精,而且对肢体百骸具有直接的助长、润养作用。但凡后天有源,先天之精则不竭,后天之筋骨得夯以实。重要的是,脾胃对形骸的作用包括气阳温煦以壮长肢体、脾胃营阴润养以坚固筋骨两方面。故笔者从古代经典理论、现代研究基础、生命的圆运动变化等几方面论述骨质疏松症"病本在脾,以阴阳两虚为要"这一观点。     

2型糖尿病合并骨质疏松相关因素的分析

目的探讨2型糖尿病合并骨质疏松的相关因素,并为进一步治疗提供相关依据。方法 2型糖尿病患者157例,男性79例,女性78例,其中分为合并骨质疏松组(OP)74例,未合并骨质疏松组(NOP)83例。分析比较这两组患者的性别、年龄、病程、体重指数(BMI)、血钙(Ca)、血磷(P)、碱性磷酸酶(ALP)、空腹血糖(FBG)、糖化血红蛋白(HBA1c)、尿微量白蛋白、血肌酐、甘油三酯(Tg)、总胆固醇(Tc)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、25羟基维生素D的差异。结果骨质疏松组与非骨质疏松组比较,性别、病程、BMI、HBA1c、血肌酐、尿微量白蛋白、25羟基维生素D有统计学差异性(P0.05),而Ca、P、ALP、FBG、Tg、Tc、HDL-C、LDL-C无统计学意义(P0.05);二元Logistic回归分析显示病程、BMI、HBA1c、25羟基维生素D与OP有关。结论病程、BMI、HBA1c、25羟基维生素D是影响2型糖尿病合并骨质疏松的相关因素。     

健脾清肝合剂防治肝癌TACE后肝功能损害的临床研究

目的 探讨健脾清肝合剂对肝癌肝动脉栓塞化疗（TACE）后肝功能损害的防治作用。方法 将86例患者随机分为治疗组和对照组各43例，治疗组在行TACE治疗前1周开始服用健脾清肝合剂，对照组在TACE治疗后出现肝功能损害时加用凯西莱口服；服药2个月后比较治疗前后肝功能变化及治疗后组间各项肝功能指标的差异。结果 对照组第1次介入后第3d血清AST、ALT均升高，与治疗前比较，差异有统计学意义（P〈0.05）；对照组第1次介入后第14d血清ALB降低，与治疗前比较，差异有统计学意义（P〈0.05）；治疗组与对照组第2次介入后第28d的AST值比较差异有统计学意义（P〈0.05）。结论 肝癌患者在行肝动脉化疗栓塞治疗时，配合服用健脾清肝合剂可在一定程度上防治TACE治疗所致的肝功能损害。     

Effect of composite Yuyin recipe on cultured human epithelial cell proliferation in vitro

Objective

To study the effect of Yuyin recipe, a Chinese composite recipe, on cultured human epithelial cell proliferation in vitro

Methods

YYR in different concentrations was added separately into the keratinocyte CoLo-16 line, after the latter had been cultured 24 hrs, to be co-cultured for different periods of time (24–72 hrs). A blank control group was set up in the meantime. Effect of YYR with different concentrations and different acting time on keratinocyte proliferation was observed by MTT method

Results

YYR in different concentrations showed significant inhibitory effect on keratinocyte CoLo-16 line in concentration-dependent and acting-time-dependent manner

Conclusion

Inhibition on over proliferation of epithelial cells may be one of the mechanisms of YYR in curing psoriasis.