Design, synthesis and triglyceride-lowering activity of tricyclic matrine derivatives for the intervention of non-alcoholic fatty liver disease.

Thirty new tricyclicmatrinic derivatives were successively synthesized and evaluated for their inhibitory activity on the accumulation of triglycerides (TG) in AML12 cells, using 12 N-m-trifluoromethylbenzenesulfonyl matrine (1) as the hit compound. Among the analogues, compound 7n possessing 11-trimethylbutylamine quaternary exerted the highest in vitro TG-lowering potency, as well as a good safety profile. 7n significantly attenuated the hepatic injury and steatosis, and ameliorated dyslipidemia and dysglycemia in the mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet.

Lactoferrin modification of berberine nanoliposomes enhances the neuroprotective effects in a mouse model of Alzheimer's disease.

Previous studies have shown that berberine has neuroprotective effects against Alzheimer's disease, including antagonizing tau phosphorylation, and inhibiting acetylcholinesterase activity and neural cell apoptosis. However, its low bioavailability and adverse reactions with conventional administration limit its clinical application. In this study, we prepared berberine nanoliposomes using liposomes characterized by low toxicity, high entrapment efficiency, and biodegradability, and modified them with lactoferrin.

Anti-hypertensive and endothelia protective effects of Fufang Qima capsule on primary hypertension via adiponectin/adenosine monophosphate activated protein kinase pathway.

Objective: To investigate the potential mechanism of the vascular remodeling effect and provide additional information about anti-hypertension activity of Fufang Qima capsule.

Methods: Spontaneous hypertensive rats (SHRs) were used to study the underlying mechanism of the anti-hypertension activity of QM. In this study, SHRs were randomly divided into 5 groups: model group, Telmisartan group (7.

Structure-activity relationship and biological evaluation of 12 N-substituted aloperine derivatives as PD-L1 down-regulatory agents through proteasome pathway.

Twenty-nine 12 N-substituted aloperine derivatives were synthesized and screened for suppression on PD-L1 expression in H460 cells, as a continuation of our work. Systematic structural modifications led to the identification of compound 6b as the most active PD-L1 modulator. Compound 6b could significantly down-regulate both constitutive and inductive PD-L1 expression in NSCLC cells, and successively enhance the cytotoxicity of co-cultured T cells against tumor cells at the concentration of 20 μM.

Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage.

So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile.

Studies on Dissipations and Residues of Indoxacarb under Different Field and Environmental Conditions.

Indoxacarb is a broad-spectrum insecticide and widely used in agriculture. The dissipations and residues of indoxacarb were researched at three different field sites in Beijing, Hunan, and Zhejiang provinces in China. Analytical methods for determining the residue of indoxacarb in paddy water, paddy soil, rice straw, rice hull, and brown rice were described.

Structure-activity relationship and hypoglycemic activity of tricyclic matrines with advantage of treating diabetic nephropathy.

Forty-three tricyclic matrinic derivatives with a unique scaffold were prepared and evaluated for their stimulation effects on glucose consumption in HepG2 cells. The structure-activity relationship was systematically elucidated for the first time. Among them, compound 17a exhibited the most promising potency, and dose-dependently increased glucose consumption in L6 myotubes.

Skin-patch of Xin Huang Pian on relieving joint symptoms in patients with acute gouty arthritis: A Randomized, Double-Blind, Active-Controlled Trial.

Aims: To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis.

Background: In China, patients with acute gouty arthritis benefit from skin patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported.

Neuroprotective Effect of Fructus broussonetiae on APP/PS1 Mice via Upregulation of AKT/β-Catenin Signaling.

Objective: To evaluate the mechanisms underlying the protective effect of Chinese herbal medicine Fructus broussonetiae (FB) in both mouse and cell models of Alzheimer's disease (AD).

Methods: APP/PS1 mice treated with FB for 2 months and vehicle-treated controls were run through the Morris water maze and object recognition test to evaluate learning and memory capacity. RNA-Seq, Western blotting, and immunofluorescence staining were also conducted to evaluate the effects of FB treatment on various signaling pathways altered in APP/PS1 mice.

circMTDH.4/miR-630/AEG-1 axis participates in the regulation of proliferation, migration, invasion, chemoresistance, and radioresistance of NSCLC.

Astrocyte elevated gene-1 (AEG-1) plays a critical role in the development, progression, and metastasis of a variety of cancers, including non-small-cell lung cancer (NSCLC). The objective of the current study is to unravel the upstream signaling of AEG-1. A cohort of 28 NSCLC tissues and 30 normal tissues were collected.

Protective effects of organic extracts of against hydrogen peroxide-induced cytotoxicity in PC12 cells.

Alpinia oxyphylla, a traditional herb, is widely used for its neuroprotective, antioxidant and memory-improving effects. However, the neuroprotective mechanisms of action of its active ingredients are unclear. In this study, we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro.

[Treatment of scapulohumeral periarthritis by Fuyang-pot warming combined with electroacupuncture stimulation].

Objective: To observe the clinical therapeutic effect of Fuyang-pot warming combined with electroacupuncture (EA) in the treatment of scapulohumeral periarthritis (SPA).

Methods: A total of 90 cases of SPA patients were randomized into EA, Fuyang-pot warming and EA plus Fuyang-pot warming (combination) groups (=30 per group). Fuyang-pot warming including pressing, mild moxibustion, scraping-pushing, cupping, tapping, etc.

Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs.

Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004-17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-speed differentiating features for facilitating target assessment. Here we present a comprehensive analysis of all these 89 targets, following the earlier studies for prospective prediction of clinical success of the targets of clinical trial drugs.

Synthesis and Evolution of Berberine Derivatives as a New Class of Antiviral Agents against Enterovirus 71 through the MEK/ERK Pathway and Autophagy.

Taking berberine (BBR) as the lead, 23 new BBR derivatives were synthesized and examined for their antiviral activities against four different genotype enterovirus 71 (EV71) strains with a cytopathic effect (CPE) assay. Structure-activity relationship (SAR) studies indicated that introduction of a suitable substituent at the 9-position might be beneficial for potency. Among them, compound exhibited most potent activities with IC values of 7.

Recurrent pregnancy loss: A summary of international evidence-based guidelines and practice.

Background: Recurrent pregnancy loss (RPL) is defined as two or more pregnancy losses. It affects <5% of couples. There are many proposed causes; however, in a significant proportion of cases, the cause is unknown.

[Chemical Characteristics and Sources of Heavy Metals in Fine Particles in Beijing in 2011-2012].

In order to investigate the chemical characteristics and sources of atmospheric heavy metals, PM samples were collected every three days during the summer of 2011 and summer of 2012. The samples were analyzed for Li, V, Cr, Mn, Co, Cu, Zn, As, Se, Ti, Ga, Ni, Sr, Cd, In, Ba, Tl, Pb, Bi, and U by ICP-MS, with an emphasis on seven major heavy metal elements (Zn, Pb, Mn, Cu, As, V, and Cr). The concentrations of Zn, Pb, Mn, Cu, As, V, and Cr were (331.

Prediction of the binding mode and resistance profile for a dual-target pyrrolyl diketo acid scaffold against HIV-1 integrase and reverse-transcriptase-associated ribonuclease H.

The rapid emergence of drug-resistant variants is one of the most common causes of highly active antiretroviral therapeutic (HAART) failure in patients infected with HIV-1. Compared with the existing HAART, the recently developed pyrrolyl diketo acid scaffold targeting both HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) is an efficient approach to counteract the failure of anti-HIV treatment due to drug resistance. However, the binding mode and potential resistance profile of these inhibitors with important mechanistic principles remain poorly understood.

Discovery and evolution of aloperine derivatives as novel anti-filovirus agents through targeting entry stage.

Preventing filoviruses in the entry stage is an attractive antiviral strategy. Taking aloperine, a Chinese natural herb with an endocyclic skeleton, as the lead, 23 new aloperine derivatives were synthesized and evaluated for their anti-filovirus activities including ebola virus (EBOV) and marburg virus (MARV) using pseudotyped virus model. Structure-activity relationship (SAR) analysis indicated that the introduction of a 12N-dichlorobenzyl group was beneficial for the potency.

Synthesis and Biological Evaluation of 12N-substituted Tricyclic Matrinic Derivatives as a Novel Family of Anti-Influenza Agents.

Background: Influenza is still a serious threat to human health with significant morbidity and mortality, so it is desirable to develop novel anti-flu drug agents with novel structures.

Objective: The main purpose of this research was to explore broad-spectrum anti-flu agents and provide antiviral stockpiles in response to potential future influenza pandemics.

Methods: Fifteen novel 12N-substituted tricyclic matrinic derivatives were synthesized and evaluated for their anti-influenza activities against H1N1 subtype taking 12N-p-cyanobenzenesulfonyl matrinane (1) as the lead.

Assessing the Performances of Protein Function Prediction Algorithms from the Perspectives of Identification Accuracy and False Discovery Rate.

The function of a protein is of great interest in the cutting-edge research of biological mechanisms, disease development and drug/target discovery. Besides experimental explorations, a variety of computational methods have been designed to predict protein function. Among these in silico methods, the prediction of BLAST is based on protein sequence similarity, while that of machine learning is also based on the sequence, but without the consideration of their similarity.

Discovery and evolution of aloperine derivatives as a new family of HCV inhibitors with novel mechanism.

Aloperine (1), a Chinese natural product with a unique endocyclic scaffold, was first identified to be a potent hepatitis C virus (HCV) inhibitor in our laboratory. Thirty-four new aloperine derivatives were designed, synthesized and evaluated for their anti-HCV activities taking 1 as the lead. Among them, compound 7f exhibited the potential potency with EC values in a micromolar range against both wild-type and direct-acting antiviral agents (DAAs)-resistant variants, and synergistically inhibited HCV replication with approved DAAs.

Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics.

Extensive efforts have been directed at the discovery, investigation and clinical monitoring of targeted therapeutics. These efforts may be facilitated by the convenient access of the genetic, proteomic, interactive and other aspects of the therapeutic targets. Here, we describe an update of the Therapeutic target database (TTD) previously featured in NAR.

Synthesis and biological evaluation of tricyclic matrinic derivatives as a class of novel anti-HCV agents.

Background: 12N-benzyl matrinic acid analogues had been identified to be a novel scaffold of anti-HCV agents with a specific mechanism, and the representative compound 1 demonstrated a moderate anti-HCV activity. The intensive structure-activity relationship of this kind of compounds is explored so as to obtain anti-HCV candidates with good druglike nature.

Results: Taking compound 1 as the lead, 32 compounds (of which 27 were novel) with diverse structures on the 11-side chain, including methyl matrinate, matrinol, matrinic butane, (Z)-methyl Δ-matrinic crotonate derivatives were synthesized and evaluated for their anti-HCV activities.

Transfer and Metabolism of Triadimefon Residues from Rape Flowers to Apicultural Products.

This paper presents a study on the transfer and metabolism of triadimefon residues from rape flowers to apicultural products. In the field trials, honeybee colonies were placed in four rape greenhouses treated with triadimefon on standard dosage. Apicultural products (pollen, honey, and royal jelly) were collected on a regular basis.