Design,Synthesis, and Cytotoxic Activities of Indole and Indazole-Based Stilbenes

To develop new highly effective anticancer agents derived from naturally occurring stilbene scaffold, in total of 24 indole and indazole-based stilbenes including 17 new compounds were designed according to molecular hybridization strategy and synthesized via Witting reaction. The cytotoxic screening results against human tumor cell lines (K562 cells and MDA-MB-231 cells) showed that indole and indazole-based stilbenes are of great interest for developing anticancer agents as eight derivatives possessed strong antiproliferative activities with IC₅₀ values less than 10 μM, and those synthetic derivatives displayed more higher cytotoxicities against K562 cells than MDA-MB-231 cells. In particular, indole-based stilbene bearing piperidine exhibited the most potent cytotoxicities against both K562 and MDA-MB-231 cells with IC₅₀ values 2.4 μM and 2.18 μM, respectively, along with a remarkable selectivity towards human normal L-02 cells. Together, the results suggested that indole and indazole-based stilbenes are promising anticancer scaffolds worthy of further investigation.     

Engeletin alleviates cerebral ischemia reperfusion-induced neuroinflammation via the HMGB1/TLR4/NF-κB network

High-mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti-inflammatory activity. Herein, we examined the mechanism of engeletin-mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dose-dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL-1β, TNF-α, IL-6 and IFN-γ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl-2 protein levels, while suppressing Bax and Cleaved Caspase-3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF-κB and attenuated nuclear transfer of nuclear factor kappa B (NF-κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF-κB inflammatory network.     

Development and validation of robust metabolism-related gene signature in the prognostic prediction of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Given metabolic reprogramming in tumours was a crucial hallmark, several studies have demonstrated its value in the diagnostics and surveillance of malignant tumours. The present study aimed to identify a cluster of metabolism-related genes to construct a prediction model for the prognosis of HCC. Multiple cohorts of HCC cases (466 cases) from public datasets were included in the present analysis. (GEO cohort) After identifying a list of metabolism-related genes associated with prognosis, a risk score based on metabolism-related genes was formulated via the LASSO-Cox and LASSO-pcvl algorithms. According to the risk score, patients were stratified into low- and high-risk groups, and further analysis and validation were accordingly conducted. The results revealed that high-risk patients had a significantly worse 5-year overall survival (OS) than low-risk patients in the GEO cohort. (30.0% vs. 57.8%; hazard ratio [HR], 0.411; 95% confidence interval [95% CI], 0.302–0.651; p < 0.001) This observation was confirmed in the external TCGA-LIHC cohort. (34.5% vs. 54.4%; HR 0.452; 95% CI, 0.299–0.681; p < 0.001) To promote the predictive ability of the model, risk score, age, gender and tumour stage were integrated into a nomogram. According to the results of receiver operating characteristic curves and decision curves analysis, the nomogram score possessed a superior predictive ability than conventional factors, which indicate that the risk score combined with clinicopathological features was able to achieve a robust prediction for OS and improve the individualized clinical decision making of HCC patients. In conclusion, the metabolic genes related to OS were identified and developed a metabolism-based predictive model for HCC. Through a series of bioinformatics and statistical analyses, the predictive ability of the model was approved.     

Insecticidal and Repellent Effects of the Essential Oils Extract from Zanthoxylum myriacanthum against Three Storage Pests

The co-storage of two or more Chinese herbal medicines can effectively prevent the herbs from the damage by pests. Thus, it is important to protect herbs and crops to study Chinese herbal medicines and their medicinal components against storage pests. This study aimed to assess the insecticidal activities and repellent effect of essential oils (EOs) extracted from fruits at different periods from Zanthoxylum myriacanthum Wall. ex Hook. f. (1 h, 2 h, 3–5 h and 5–7 h), and their major compounds against three kinds of pests (Tribolium castaneum, Lasioderma serricorne, and Liposcelis bostrychophila). The results of gas chromatography-mass spectrometer analysis revealed homomyrtenol (22.56 %, 28.01 %, 28.48 % and 28.41 %, respectively) and p-cymene (30.58 %, 13.95 %, 24.97 % and 6.85 %, respectively) were the common major compounds of the EOs at 1 h, 2 h, 3–5 h, and 5–7 h. m-Cymene contents in EOs of fruits, 1 h, 2 h and 3–5 h were 3.85 %, 0.95 %, 6.71 %, and 6.15 %, respectively. According to Principal component analysis (PCA), the composition of fruits′ EO was significantly different from other EOs due to the different collection times. The bio-assays showed that EOs and major compounds were toxic to all three pests, but the fumigation effect on L. bostrychophila was not noticeable. EOs extracted at different times had a repellent effect on the three pests at the highest concentration (78.63 nL/cm²), but the attractive effects of the EOs of 3–5 h, 5–7 h, and p-cymene were observed at the low concentrations (3.15, 0.63 and 0.13 nL/cm²). Our results suggest that Z. myriacanthum have the potential to be developed as biological insecticides.     

小兴安岭兴安落叶松泥炭藓沼泽植物的主要微量元素

小兴安岭兴安落叶松、泥炭藓沼泽是我国典型贫营养型沼泽。沼泽中树木生长发育不良,泥炭藓和常绿小灌木发育十分良好。这与沼泽水文状况和泥炭中营养元素和微量元素有关。各种植物的主要微量元素硼、铜、钴、锰、锌等含量不同,植物的不同器官中的含量亦不同,而且随季节而变化。狭叶杜香和甸杜的主要微量元素含量特点及其季节变化规律基本相似,两种泥炭藓相似,都与兴安落叶松有明显的区别。 本文重点探讨植物体内主要微量元素及其含量变化规律,为揭示贫营养型森林沼泽生态、为合理利用与改造沼泽提供依据。     

ent-Pimarane Diterpenes from the Aerial Parts of Siegesbeckia pubescens

Five new ent-pimarane diterpenes ( 1 – 5 ) and five known analogs ( 6 – 10 ) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC₅₀ values of 16.35±2.59 and 18.86±4.83 μM, respectively.     

The Ethanol Extract of Syringa oblata Heartwood,a Mongolian Folk Medicine Containing Major Lignans,Exerts Analgesic and Sedative Effects on Mice

The heartwood of Syringa oblata Lindl. (SO) is one of Mongolian folk medicines to treat insomnia and pain, while its pharmacological evaluation and underlying mechanism remain unclear. In this study, the sedative effect of ethanol extract of SO (ESO) was evaluated with the locomotor activity test and the threshold dose of pentobarbital sodium-induced sleep test in mice, and the hot plate test, acetic acid-induced writhing test, and formalin test in mice were used to evaluate its analgesic effect. The underlying mechanism of ESO analgesia was explored by RT-PCR and western blot analysis, which is associated with the regulation of the NF-κB signaling pathway. Besides, the main constituents of ESO were characterized by LC/MS data analysis and comparison with isolated pure compounds. The current findings brought evidence for clinical application and further pharmacological and phytochemical studies on SO.     

诱发小麦成熟胚愈伤组织及其再生植株抗盐性变异的研究

本研究以普通小麦成熟胚为起始材料,以平阳霉素(PYM)和正定霉素(ZDM)为诱变剂。发现不同基因型对药物的敏感性不同,其中对药物敏感的在含盐筛选培养基上的存活率高。在诱导培养基内添加一定量的诱变剂可以产生耐盐变异。这种抗性愈伤组织转入与筛选培养基含盐量相同的分化培养基,比较容易产生耐盐再生植株。其M_1、M_2代较亲本系表现株高降低,穗长变短、籽粒饱满度也差;M_1代的结实率仅有5.5%,M_2代恢复到40.9%。利用M_1代和亲本系实生苗叶片,进行脯氨酸含量测定。发现耐盐变异株在无盐的Hoagland溶液中,游离脯氨酸的含量超过亲本系,对盐胁迫不敏感,其耐受力强于对照,具有一定的抗盐稳定性。     

Picroside III,an Active Ingredient of Picrorhiza scrophulariiflora,Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity

This study aims to explore the protective effects of Picroside III, an active ingredient of Picrorhiza scrophulariiflora, on the intestinal epithelial barrier in tumor necrosis factor-α (TNF-α) induced Caco-2 cells and dextran sulfate sodium (DSS) induced colitis in mice. Results show that Picroside III significantly alleviated clinical signs of colitis including body weight loss, disease activity index increase, colon shortening, and colon tissue damage. It also increased claudin-3, ZO-1 and occludin expressions and decreased claudin-2 expression in the colon tissues of mice with colitis. In vitro, Picroside III also significantly promoted wound healing, decreased the permeability of cell monolayer, upregulated the expressions of claudin-3, ZO-1 and occludin and downregulated the expression of claudin-2 in TNF-α treated Caco-2 cells. Mechanism studies show that Picroside III significantly promoted AMP-activated protein kinase (AMPK) phosphorylation in vitro and in vivo, and blockade with AMPK could significantly attenuate the upregulation of Picroside III in ZO-1 and occludin expressions and the downregulation of claudin-2 expression in TNF-α treated Caco-2 cells. In conclusion, this study demonstrates that Picroside III attenuated DSS-induced colitis by promoting colonic mucosal wound healing and epithelial barrier function recovery via the activation of AMPK.