[Arctigenin mitigates vascular endothelial injury in rats with pregnancy-induced hypertension via autophagy-NLRP3 inflammasome pathway].

This study aims to investigate the effect and mechanism of arctigenin(ARC) in the treatment of vascular endothelial injury in rats with pregnancy-induced hypertension(PIH). Fifty SD rats pregnant for 12 days were randomly assigned into a control group, a model group, an ARC group, a rapamycin(RAP, autophagy inducer) group, and an ARC+3-methyladenine(3-MA, autophagy inhibitor) group, with 10 rats in each group. The rats in the other groups except the control group were intraperitoneally injected with nitrosyl-L-arginine methyl ester(50 mg·kg~(-1)·d~(-1)) to establish the PIH model on the 13th day of pregnancy. On the 15th day of pregnancy, the rats in ARC, RAP, and ARC+3-MA groups were intraperitoneally injected with ARC(50 mg·kg~(-1)·d~(-1)), RAP(1 mg·kg~(-1)·d~(-1)), and 3-MA(15 mg·kg~(-1)·d~(-1))+ARC(50 mg·kg~(-1)·d~(-1)), respectively. The pregnant rats in the control group and the model group were intraperitoneally injected with the same amount of normal saline. The blood pressure and 24 h urine protein(24 h-UP) of pregnant rats in each group were measured before and after intervention. Cesarean section was performed to terminate pregnancy on day 21, and the body weight and body length of fetal rats were compared among groups. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes of placenta. The expression of endothelin-1(ET-1) and endothelial nitric oxide synthase(eNOS) in placenta was detected by immunohistochemistry. The serum levels of ET-1 and nitric oxide(NO) were determined with corresponding kits. The expression of microtubule-associated protein 1 light chain 3(LC3), Beclin-1, NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein with CARD domain(ASC), caspase-1, interleukin(IL)-1ß, and IL-18 was determined by immunofluorescence and Western blot. The level of reactive oxygen species(ROS) in placenta was measured by fluorescence staining. The results showed that on day 12 of pregnancy, the blood pressure and 24 h-UP had no significant differences among groups. On days 15, 19, and 21, the blood pressure and 24 h-UP in the model group were higher than those in the control group(P<0.05). On days 19 and 21, the blood pressure and 24 h-UP in ARC group and RAP group were lower than those in the model group(P<0.05), and they were higher in the ARC+3-MA group than in the ARC group(P<0.05). On day 21, the model group had lower body weight and body length of fetal rats(P<0.05), higher serum level of ET-1, and lower serum level of NO(P<0.05) than the control group. Moreover, the placental tissue showed typical pathological damage, down-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1 and eNOS(P<0.05), up-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1ß, and IL-18(P<0.05), and elevated ROS level. Compared with the model group, ARC and RAP groups showed increased body weight and body length of fetal rats(P<0.05), lowered serum level of ET-1, elevated serum level of NO(P<0.05), reduced pathological damage of placental tissue, up-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and eNOS(P<0.05), down-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1ß, and IL-18(P<0.05), and lowered ROS level. Compared with ARC group, 3-MA reversed the effects of ARC on the above indicators. In conclusion, ARC can inhibit the activation of NLRP3 inflammasome and mitigate vascular endothelial damage in PIH rats by inducing autophagy of vascular endothelial cells.

A narrative review of molecular mechanism and therapeutic effect of cannabidiol (CBD).

Cannabidiol (CBD) is an abundant non-psychoactive phytocannabinoid in cannabis extracts which has high affinity on a series of receptors, including Type 1 cannabinoid receptor (CB1), Type 2 cannabinoid receptor (CB2), GPR55, transient receptor potential vanilloid (TRPV) and peroxisome proliferator-activated receptor gamma (PPARγ). By modulating the activities of these receptors, CBD exhibits multiple therapeutic effects, including neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, analgesic and anticancer properties. CBD could also be applied to treat or prevent COVID-19 and its complications. Here, we provide a narrative review of CBD's applications in human diseases: from mechanism of action to clinical trials.

[Current studies on quality of Chinese patent drugs with consistency as core and discussions on new high-quality evaluation model].

The consistency of quality on Chinese patent drugs is a hotspot and difficulty in the control of traditional Chinese medicine preparations, and has become one of the bottlenecks restricting its internationalization. Based on the analysis of current studies on quality and problems of Chinese patent drugs, this paper explored relevant methods of quality evaluation on Chinese patent drugs and possible factors affecting the consistency of quality in the pharmaceutical cycle by consulting relevant literatures about quality evaluation methods and consistency control techniques of large-scale Chinese patent drugs. And it put forward the evaluation system on high-quality Chinese patent drugs with "consistency" as the core, so as to promote the overall improvement of the quality of Chinese patent drugs, guide the rational price of Chinese patent drugs of the same species, and provide a new reference model for the quality evaluation of Chinese patent drug.

[Grade evaluation of Sophorae Tonkinensis Radix et Rhizoma based on quality constant evaluation method].

The traditional Chinese medicine(TCM) quality constant herbal slices evaluation method was applied to evaluate the grade of Sophorae Tonkinensis Radix et Rhizoma based on the combination of traditional character identification and modern scientific and technological methods. The TCM quality constant evaluation method was used to determine the appearance and index content of medicinal slices, calculate the quality constant and percentile quality constant of Sophorae Tonkinensis Radix et Rhizoma from different sources, and discuss their classification. The quality constants of 15 batches of Sophorae Tonkinensis Radix et Rhizoma slices were between 0.004 and 0.063. The slices with the percentage quality constant ≥80% were classified as the first grade; those with the percentage quality constant ≥50% and <80% were classified as the second grade; and those with the percentage quality constant <50% were classified as the third grade. Then the slices with the quality constant ≥0.050 were classified as the first grade; those with the quality constant ≥0.032 and <0.050 were classified as the second grade; and those with the quality constant <0.032 were classified as the third grade. According to the results, the 15 batches of Sophorae Tonkinensis Radix et Rhizoma slices were divided into 1 batch of the first grade, 4 batches of the second grade, and 10 batches of the third grade. The quality constant evaluation method established is scientific, objective, simple and feasible. The application of the method in Sophorae Tonkinensis Radix et Rhizoma slices has reasonable results, which is helpful to promote the classification of Sophorae Tonkinensis Radix et Rhizoma and promotes the high-quality application of Sophorae Tonkinensis Radix et Rhizoma.

[Evaluation and analysis of high-quality products of Liuwei Dihuang Pills].

Liuwei Dihuang Pills is a typical traditional Chinese medicine with "the same product made by many manufacturers". The quality and price of products made in various factories was different obviously. In this study, the quality differences of Liuwei Dihuang Pills were evaluated over multi-dimensions and throughout the whole production cycle involving raw materials, production process, quality control and post-marketing re-studies based on the "Chinese patent medicine evaluation standard with quality at the core" established earlier by our research group. The research results showed that the product quality of various manufacturers was significantly different, and the product quality was positively correlated with the market shares of enterprises, indicating that enterprises with more market shares paid more attention to product quality; and the sales determined the concern degree of enterprises on products, which was in line with general cognition. During the single-item evaluation of Liuwei Dihuang Pills, the score of raw material selection was relatively low, and the enterprises paid less attention to the initial raw materials. The whole production process was better, and the national compulsory implementation of "Production Quality Management Standard"(GMP) had a positive effect in improving product quality. Quality control could basically guarantee product quality. Intelligent manufacturing promoted by the government was beneficial to ensure product uniformity. The score rate of "quality evaluation" item was basically qualified, which indicated that the quality control level of Liuwei Dihuang Pills was acceptable as a whole, but there was still room for improvement. "Re-evaluation and Brand Construction" had the lowest scores, reflecting that enterprises did not pay enough attention to in-depth study and re-evaluation of "the same product made by many manufacturers". The evaluation results were in line with expectations, provided a reference example for the evaluation of high-quality Chinese patent medicine, a basis for the high-quality and good price of Chinese patent medicine, scientific data for improving medical insurance bidding, and thus facilitated promoting the healthy development of the traditional Chinese medicine industry.

[Effect of rosmarinic acid from Sarcandra glabra in inhibiting proliferation and migration and inducing apoptosis of MDA-MB-231 cells via regulation of expressions of Bcl-2 and Bax].

Rosmarinic acid is one of anti-tumor ingredients in the Sarcandra glabra. After treatment with 0, 10, 30, 90, 270 and 810 µmol·L⁻¹ rosmarinic acid for 24, 48, 72 hours respectively, the inhibitory effects on MCF-7 and MDA-MB-231 cells were observed by CCK-8 and cell wound healing test. No significant inhibition effecton proliferation and migration was observed in MCF-7 cell. However, 90, 270 and 810 µmol·L⁻¹ rosmarinic acid could inhibit the proliferation and migration of MDA-MB-231 cells in a dose-dependent and time-dependent manner. Flow cytometry was further used to detect apoptosis ratios of MDA-MB-231 cells after Annexin V-FITC/PI staining, and significant apoptosis was observed after rosmarinic acid treatment. Real-time PCR and Western blot tests were carried out to detect the expressions of apoptosis-related genes. The down-regulation of the Bcl-2 expression and the up-regulation of the Bax expression were observed in MDA-MB-231 cells after rosmarinic acid treatment. The results suggested that rosmarinicacid can inhibit the proliferation and migration, and induce the apoptosis of MDA-MB-231 cells, which may be correlated with the down-regulation of Bcl-2 gene and the up-regulation of Bax gene.

Value of combined detection of serum carcinoembryonic antigen, carbohydrate antigen 199 and tumor M2 pyruvate kinase for the diagnosis of colon cancer / 新乡医学院学报

Objective To investigate the clinical value of combined detection of serum carcinoembryonic antigen (CEA),carbohydrate antigen 199 (CA199) and tumor type M2 pyruvate kinase (TuM2-PK) for the diagnosis of early colon cancer.Methods A total of 137 patients with colon cancer in the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine from February 2014 to November 2016 were selected as observation group,87 patients with benign colon disease were selected as control group,and 75 healthy subjects were selected as health group.The levels of serum CEA and CA199 were detected by electrochemiluminescence,and serum TuM2-PK level was determined by quantitative enzyme-linked immunosorbent assay.The diagnostic value of single and combined detection on early colon cancer were compared.Results The levels and positive expression rate of serum CEA,CA199 and TuM2-PK in the observation group were significantly higher than those in the control group and the health group(P ＜0.05).There was no significant difference in the levels and positive expression rate of serum CEA,CA 199,TuM2-PK between the control group and the health group (P ＜ 0.05).The sensitivity and Youden index of combined detection of CEA,CA199 and TuM2-PK were better than those of single or two indexes detection(P ＜0.05).The specificity of combined detection of CEA,CA199 and TuM2-PK was better than that of single detection and combined detection of CEA,CA199 (P ＜ 0.05).The combined detection of two or three indexes in CEA,CA199 and TuM2-PK had certain diagnostic value for colon cancer,the area under the receiver operating characteristic curve ≥0.70;and the area under the receiver operating characteristics curve of the combined detection of CEA,CA199 and TuM2-PK was the largest.Conclusion The combined detection of CEA,CA199 and TuM2-PK has the high diagnostic value for colon cancer.

Remarkably Stereospecific Utilization of ATP α,ß-Halomethylene Analogues by Protein Kinases.

ATP analogues containing a CXY group in place of the α,ß-bridging oxygen atom are powerful chemical probes for studying ATP-dependent enzymes. A limitation of such probes has been that conventional synthetic methods generate a mixture of diastereomers when the bridging carbon substitution is nonequivalent (X ≠ Y). We report here a novel method based on derivatization of a bisphosphonate precursor with a d-phenylglycine chiral auxiliary that enables preparation of the individual diastereomers of α,ß-CHF-ATP and α,ß-CHCl-ATP, which differ only in the configuration at the CHX carbon. When tested on a dozen divergent protein kinases, these individual diastereomers exhibit remarkable diastereospecificity (up to over 1000-fold) in utilization by the enzymes. This high selectivity can be exploited in an enzymatic approach to obtain the otherwise inaccessible diastereomers of α,ß-CHBr-ATP. The crystal structure of a tyrosine kinase Src bound to α,ß-CHX-ADP establishes the absolute configuration of the CHX carbon and helps clarify the origin of the remarkable diastereospecificity observed. We further synthesized the individual diastereomers of α,ß-CHF-γ-thiol-ATP and demonstrated their utility in labeling a wide spectrum of kinase substrates. The novel ATP substrate analogues afforded by these two complementary strategies should have broad application in the study of the structure and function of ATP-dependent enzymes.

[Chemical constituents of Scurrula parasitica].

A new triterpenoid ester, 7ß-hydroxyl-hop-22(29)-en-3ß-O-palmitate (1), was isolated from the stems and leaves of Scurrula parasitica parasitic on Nerium indicum, along with nine known compounds, uvaol (2), 3-epi-ursolic acid (3), 3ß-hydroxyl-hop-22(29)-ene (4), 3ß, 15α-dihydroxyl-lup-20(29)-ene (5), lup-20(29)-en-3-O-α-D-glucoside (6), stigmasterol-3-O-ß-D-glucoside (7), digitoxin-3-O-α-D-glucoside (8), behenic acid (9), octacosyl alcohol (10). Their structures were elucidated using a combination of 1D and 2D NMR techniques (COSY, HMQC, and HMBC) and HR-ESI-MS analyses. Compounds 2-10 were isolated from this plant for the first time.

Facile Fabrication of Near-Infrared-Resonant and Magnetic Resonance Imaging-Capable Nanomediators for Photothermal Therapy.

Although many techniques exist for fabricating near-infrared (NIR)-resonant and magnetic resonance imaging (MRI)-capable nanomediators for photothermal cancer therapy, preparing them in an efficient and scalable process remains a significant challenge. In this report, we exploit one-step siloxane chemistry to facilely conjugate NIR-absorbing satellites onto a well-developed polysiloxane-containing polymer-coated iron oxide nanoparticle (IONP) core to generate dual functional core-satellite nanomediators for photothermal therapy. An advantage of this nanocomposite design is the variety of potential satellites that can be simply attached to impart NIR resonance, which we demonstrate using NIR-resonant gold sulfide nanoparticles (Au2SNPs) and the NIR dye IR820 as two example satellites. The core-satellite nanomediators are fully characterized by using absorption spectra, dynamic light scattering, ζ potential measurements, and transmission electron microscopy. The enhanced photothermal effect under the irradiation of NIR laser light is identified through in vitro solutions and in vivo mice studies. The MRI capabilities as contrast agents are demonstrated in mice. Our data suggest that polysiloxane-containing polymer-coated IONPs can be used as a versatile platform to build such dual functional nanomediators for translatable, MRI-guided photothermal cancer therapy.

Identification of a broad-spectrum inhibitor of viral RNA synthesis: validation of a prototype virus-based approach.

There are no approved therapeutics for the most deadly nonsegmented negative-strand (NNS) RNA viruses, including Ebola (EBOV). To identify chemical scaffolds for the development of broad-spectrum antivirals, we undertook a prototype-based lead identification screen. Using the prototype NNS virus, vesicular stomatitis virus (VSV), multiple inhibitory compounds were identified. Three compounds were investigated for broad-spectrum activity and inhibited EBOV infection. The most potent, CMLDBU3402, was selected for further study. CMLDBU3402 did not show significant activity against segmented negative-strand RNA viruses, suggesting proscribed broad-spectrum activity. Mechanistic analysis indicated that CMLDBU3402 blocked VSV viral RNA synthesis and inhibited EBOV RNA transcription, demonstrating a consistent mechanism of action against genetically distinct viruses. The identification of this chemical backbone as a broad-spectrum inhibitor of viral RNA synthesis offers significant potential for the development of new therapies for highly pathogenic viruses.

Observation on effects of aconitine via acupoint injection in rabbits.

OBJECTIVE: To investigate the ability of the pericardium meridian (PM) to mitigate or enhance the cardiotoxic effects of aconitine injected at specific acupoint and non-acupoint sites in rabbits. METHODS: This study consisted of 3 experiments that were designed to test the effects of injection of 30 µg/kg of aconitine at acupoints on the PM (Test 1), at non-acupoint sites on the PM (Test 2), and at acupoints on other meridians and non-meridian sites (Test 3). In Test 1, 24 rabbits were randomly assigned to receive injections at Quze (PC3), Tianquan (PC2), or intramuscularly. In Test 2, 24 rabbits were randomly assigned to receive injections of aconitine at non-acupoint I, non-acupoint II, or intramuscularly. In Test 3, 48 rabbits were randomly assigned to receive injections at Neiguan (PC6), Sanyinjiao (SP6), Yangjiao (GB35), a non-meridian and non-acupoint site (NMNA), intravenously, and intramuscularly. Electrocardiographs of the rabbits were performed before, during and after injection to determine the incidence of arrhythmia, latency of ventricular rhythm, and recovery rate after aconitine injection. The recovery time index and extent of arrhythmia scores were calculated. RESULTS: In all groups the incidence of arrhythmia was 100%, and the latency of ventricular rhythm was less than 30 min. In Tests 1 and 2, the recovery rates of the Quze and non-acupoint II groups were significantly higher than those of the muscular group (P < 0.05). In Test 3, the recovery time index and extent of arrhythmia scores of the Neiguan group were low. There were no significant differences between the other acupoint groups, or the NMNA group, when compared with the group receiving aconitine intramuscularly. CONCLUSIONS: Acupoints or non-acupoints along the PM could reduce the severity of the arrhythmia induced by aconitine in healthy rabbits. Meridians play an important role in protecting body functions.