A non-invasive method to determine the pluripotent status of stem cells by culture medium microRNA expression detection.

To precisely determine the type and status of cells is an important prerequisite for basic researches and regenerative medicine involving stem cells or differentiated cells. However, the traditional destructive cell status examination methods have many limitations, mainly due to the heterogeneity of cells under the reprogramming or differentiation/trans-differentiation process. Here we present a new method to non-destructively determine the pluripotent level of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), or the types of differentiated cells.

CD36 is a co-receptor for hepatitis C virus E1 protein attachment.

The cluster of differentiation 36 (CD36) is a membrane protein related to lipid metabolism. We show that HCV infection in vitro increased CD36 expression in either surface or soluble form. HCV attachment was facilitated through a direct interaction between CD36 and HCV E1 protein, causing enhanced entry and replication.

SAR evolution and discovery of benzenesulfonyl matrinanes as a novel class of potential coxsakievirus inhibitors.

Materials & Methods: Fifty-one novel 12N-substituted matrinic acid derivatives were synthesized and evaluated for their anti-coxsackievirus B3 activities.

Results: Structure-activity relationship studies revealed that the 11-side chain could be determinant for the selectivity index by adjusting overall lipophilicity, and 11-butane was the best one for both potency and druggability. The optimized 35d showed the broad-spectrum anti-coxsackieviruse effects, an excellent pharmacokinetics and a good safety profile.

Indole alkaloid glucosides from the roots of Isatis indigotica.

Five new indole alkaloid glucosides named isatindigotindolosides A-E (1-5), along with three known analogs (6-8), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including the absolute configurations were determined based on comprehensive spectroscopic data analysis, combined with chemical methods and electronic circular dichroism spectra calculations. In the preliminary assays, compounds 1, 6 and 7 showed antiviral activity against influenza virus A/Hanfang/359/95 (H3N2) with IC50 values of 14.

Glucosylated caffeoylquinic acid derivatives from the flower buds of Lonicera japonica.

Three new glucosylated caffeoylquinic acid isomers (1-3), along with six known compounds, have been isolated from an aqueous extract of the flower buds of Lonicera japonica. Structures of the new compounds were determined by spectroscopic and chemical methods as (-)-4-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (1), (-)-3-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (2), and (-)-5-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (3), respectively. In the preliminary in vitro assays, two known compounds methyl caffeate and 2'-O-methyladenosine showed inhibitory activity against Coxsackie virus B3 with IC50 values of 3.

Synthesis and antiviral activity of a series of novel N-phenylbenzamide and N-phenylacetophenone compounds as anti-HCV and anti-EV71 agents.

A series of novel N-phenylbenzamide and N-phenylacetophenone compounds were synthesized and evaluated for their antiviral activity against HCV and EV71 (strain SZ-98). The biological results showed that three compounds (23, 25 and 41) exhibited considerable anti-HCV activity (IC50=0.57-7.

Two cases of macrodactyly of the foot: relevance in pediatric orthopedics.

Congenital enlargement of one or several digits of the foot, known as macrodactyly, is a rare malformation. Macrodactyly impedes foot development and affects function and gait. Here, we describe a surgical technique used to correct macrodactyly in two pediatric patients.

Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses.

Influenza is still a serious threat to human health with significant morbidity and mortality. The emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. Traditional Chinese medicines (TCMs) may be an alternative to overcome the challenge.

Antitumor activity of a novel survivin siRNA.

Breast cancer resistance to therapy can result from expression of antiapoptotic genes. Survivin is an antiapoptotic gene that is over expressed in most human tumors. RNA interference using short interfering RNA (siRNA) can be used to specifically inhibit survivin expression.

Silencing of Survivin Expression Leads to Reduced Proliferation and Cell Cycle Arrest in Cancer Cells.

Survivin is an anti-apoptotic gene that is overexpressed in most human tumors. RNA interference using short interfering RNA (siRNA) can be used to specifically inhibit survivin expression. Tumor cells were treated with a newly designed survivin siRNA, which was modified with 2'-OMe.

Fatty acid modified octa-arginine for delivery of siRNA.

Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Four fatty acids derivatives of octa-arginine (R8) were synthesized and evaluated for the delivery of siRNA into hepatocellular carcinoma Hep G2 and human lung adenocarcinoma A549 cells. The results showed that the long chain acid oleic acid or stearic acid derivatives of R8, OA-R8 and StA-R8, were more efficient in siRNA complexation and form nanoparticles with greater stability compared to the native R8.

Establishment of a High-Throughput Assay to Monitor Influenza A Virus RNA Transcription and Replication.

Influenza A virus (IAV) poses significant threats to public health because of the recent emergence of highly pathogenic strains and wide-spread resistance to available anti-influenza drugs. Therefore, new antiviral targets and new drugs to fight influenza virus infections are needed. Although IAV RNA transcription/replication represents a promising target for antiviral drug development, no assay ideal for high-throughput screening (HTS) application is currently available to identify inhibitors targeting these processes.

Antiviral Matrine-Type Alkaloids from the Rhizomes of Sophora tonkinensis.

Three new matrine-type alkaloids, (+)-5α-hydroxyoxysophocarpine (1), (-)-12β-hydroxyoxysophocarpine (2), and (+)-5α-hydroxylemannine (3), along with 14 known analogues, (-)-sophocarpine (4), (-)-5α-hydroxysophocarpine (5), (-)-9α-hydroxysophocarpine (6), (+)-12α-hydroxysophocarpine (7), (-)-12β-hydroxysophocarpine (8), (+)-oxysophocarpine (9), (+)-matrine (10), (+)-sophoranol (11), (+)-9α-hydroxymatrine (12), (-)-14β-hydroxymatrine (13), (+)-oxymatrine (14), (+)-5α-hydroxyoxymatrine (15), (-)-14β-hydroxyoxymatrine (16), and (+)-sophoramine (17), were isolated from the rhizomes of Sophora tonkinensis. Their structures were elucidated via spectrometric data analyses, and the absolute configurations were established by single-crystal X-ray diffraction and ECD data. Alkaloids 2, 6, 11, and 13 exhibited antiviral activity against the Coxsackie virus B3 (CVB3), with IC50 values of 26.

Antiviral glycosidic bisindole alkaloids from the roots of Isatis indigotica.

Seven new glycosidic bisindole alkaloids, isatindigobisindolosides A-G (1-7), were isolated from an aqueous extract of the Isatis indigotica roots. Their structures including absolute configurations were determined by spectroscopic and chemical methods, together with calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory. In the NMR spectra of 1-3, it is found that integration of H-2 and intensity of C-2 are affected not only by a substitution group at C-2 but also by solvents.

Structure-activity relationship of N-benzenesulfonyl matrinic acid derivatives as a novel class of coxsackievirus B3 inhibitors.

A novel series of N-benzenesulfonyl matrinic amine/amide and matrinic methyl ether analogues were designed, synthesized and evaluated for their in vitro anti-coxsackievirus B3 (CVB3) activities. The structure-activity relationship (SAR) studies revealed that introduction of a suitable amide substituent on position 4' could greatly enhance the antivirus potency. Compared to the lead compounds, the newly synthesized matrinic amide derivatives 21c-d and 21j exhibited stronger anti-CVB3 activities with lower micromolar IC50 from 2.

Bioactive Sesquiterpenes and Lignans from the Fruits of Xanthium sibiricum.

Seven new sesquiterpenes (1, 3-8), a new sesquiterpene natural product (2), and two new lignans (9 and 10), together with 15 known compounds, were isolated from the fruits of Xanthium sibiricum. The structures of the new compounds were established by NMR spectroscopic analysis, ECD calculations, and Mo2(OAc)4-induced circular dichroism, with the structures of 1 and 4 confirmed by single-crystal X-ray diffraction. Compound 1 is the first example of a 3/5/6/5 tetracyclic eudesmane sesquiterpene lactone formed at C-6 and C-7.

Total Syntheses of (-)-Spirooliganones A and B and Their Diastereoisomers: Absolute Stereochemistry and Inhibitory Activity against Coxsackie Virus B3.

To investigate the effects of configuration on bioactivity, spirooliganones A and B and their six diastereoisomers (1-8) were synthesized in 11 steps. The key benzopyran core was assembled by intermolecular [4 + 2] hetero-Diels-Alder cycloaddition between (-)-sabinene and o-quinone methide, which was generated from the corresponding o-hydroxybenzyl alcohol. After establishing the absolute configuration, the inhibitory activities of spirooliganones 1-8 against Coxsackie virus B3 were evaluated, and the primary structure-activity relationships were analyzed.

[The recent advances in the host targets of anti-influenza drugs].

The challenge of the emergence of drug-resistant influenza strains, which is caused by wide spread utilization of direct-acting antivirals (DAAs), accelerates the research and exploration towards host targeted agents. In contrast to DAAs targeting viral replication components, host targeted agents, which regulate host factors and pathways linked to viral replication, can interfere the replication of influenza. Additionally, the innate immune system is activated by influenza during the early stage of infection, so manipulating the innate immune response may prevent the viral infection.

Formononetin inhibits enterovirus 71 replication by regulating COX- 2/PGE₂ expression.

Background: The activation of ERK, p38 and JNK signal cascade in host cells has been demonstrated to up-regulate of enterovirus 71 (EV71)-induced cyclooxygenase-2 (COX-2)/ prostaglandins E2 (PGE₂) expression which is essential for viral replication. So, we want to know whether a compound can inhibit EV71 infection by suppressing COX-2/PGE₂ expression.

Methods: The antiviral effect of formononetin was determined by cytopathic effect (CPE) assay and the time course assays.

[Recombinant human interferon alpha 2b broad-spectrum anti-respiratory viruses pharmacodynamics study in vitro].

This study is to investigate the effect of recombinant human interferon alpha 2b against broad-spectrum respiratory viruses in vitro. At the cellular level, the effect of the recombinant human interferon alpha 2b on influenza A virus was detected using real-time fluorescence quantitative RT-PCR. The effects of the recombinant human interferon alpha 2b on influenza B virus, parainfluenza virus, respiratory syncytial virus (RSV) and coronavirus were detected using cytopathic effect (CPE) method.

Novel N-benzenesulfonyl sophocarpinol derivatives as coxsackie B virus inhibitors.

Novel N-benzenesulfonyl sophocarpinic acid/ester and sophocarpinol derivatives were synthesized and evaluated for their antienteroviral activities against coxsackievirus type B3 (CVB3) from sophocarpine (1), a natural medicine isolated from Chinese herb. Structure-activity relationship (SAR) analysis revealed that the double bond and its geometrical configuration and position at the C-11 attachment did not greatly affect the potency. Among these derivatives, sophocarpinol 24d exerted the promising activities against not only CVB3 but also CVB1, CVB2, CVB5, and CVB6 with IC50 ranging from 0.

m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency.

N(6)-methyladenosine (m(6)A) has been recently identified as a conserved epitranscriptomic modification of eukaryotic mRNAs, but its features, regulatory mechanisms, and functions in cell reprogramming are largely unknown. Here, we report m(6)A modification profiles in the mRNA transcriptomes of four cell types with different degrees of pluripotency. Comparative analysis reveals several features of m(6)A, especially gene- and cell-type-specific m(6)A mRNA modifications.

Brain areas activated by uncertain reward-based decision-making in healthy volunteers.

Reward-based decision-making has been found to activate several brain areas, including the ventrolateral prefrontal lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three degrees of uncertainty in a reward-based decision-making task (certain, risky, and ambiguous). The tasks were presented using a brain function audiovisual stimulation system.

Synthesis and antiviral activity of some novel indole-2-carboxylate derivatives.

A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that some of the synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compound 8f showed the highest SI value (17.

The antiviral effect of jiadifenoic acids C against coxsackievirus B3.

Coxsackievirus B type 3 (CVB3) is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM) and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases.