Subacute infective endocarditis due to : a case report and review of the literature.

, a rare emerging pathogen, can cause fungemia often related to immunosuppression or intravenous devices. Herein, we report the case of a 58-year-old woman with subacute infective endocarditis due to identified by blood fungal culture and whole-genome sequencing, who was treated with antifungals, mitral replacement and endocardial vegetation removal surgery.

Targeted treprostinil delivery inhibits pulmonary arterial remodeling.

Introduction: Pulmonary arterial hypertension (PAH) is a fatal disease caused by the progressive remodeling of pulmonary arteries (PAs). Treprostinil (TPS) is a tricyclic benzidine prostacyclin clinically used for PAH treatment. However, due to low bioavailability, short half-times, and severe systemic side effects, TPS efficacy remains limited.

Azilsartan ameliorates ventricular hypertrophy in rats suffering from pressure overload-induced cardiac hypertrophy by activating the Keap1-Nrf2 signalling pathway.

Objectives: Investigate if azilsartan protects against myocardial hypertrophy by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated pathways.

Methods: Abdominal aortic constriction (AAC)-induced cardiac hypertrophy in rats was applied. Azilsartan or vehicle was administered daily for 6 weeks in sham or AAC rats.

Evolutionary histories of coxsackievirus B5 and swine vesicular disease virus reconstructed by phylodynamic and sequence variation analyses.

Coxsackievirus (CV)-B5 is a common human enterovirus reported worldwide; swine vesicular disease virus (SVDV) is a porcine variant of CV-B5. To clarify the transmission dynamics and molecular basis of host switching between CV-B5 and SVDV, we analysed and compared the VP1 and partial 3D gene regions of these two viruses. Spatiotemporal dynamics of viral transmission were estimated using a Bayesian statistical inference framework.

Synthesis and In Vitro Anti-Influenza Virus Evaluation of Novel Sialic Acid (C-5 and C-9)-Pentacyclic Triterpene Derivatives.

The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates.

Synthesis of novel pentacyclic triterpene-Neu5Ac2en derivatives and investigation of their anti-influenza entry activity.

Sialic acid derivatives, analogs, and their conjugates are important pharmacophores. Modification of the C-4 hydroxyl group of sialic acid can lead to derivatives, such as zanamivir, with potent anti-influenza activities. Herein, we described the synthesis of C-4-modified sialic acid derivatives conjugation with naturally derived pentacyclic triterpenes, which are active ingredients of traditional Chinese medicine, and the evaluation of their anti-influenza virus activity in MDCK cells.

Phylodynamic Characterization of an Ocular-Tropism Coxsackievirus A24 Variant.

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis.

Design, synthesis and biological evaluation of novel L-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors.

Since the influenza viruses can rapidly evolve, it is urgently required to develop novel anti-influenza agents possessing a novel mechanism of action. In our previous study, two pentacyclic triterpene derivatives (Q8 and Y3) have been found to have anti-influenza virus entry activities. Keeping the potential synergy of biological activity of pentacyclic triterpenes and l-ascorbic acid in mind, we synthesized a series of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives (18-26, 29-31, 35-40 and 42-43).

Phylodynamic reconstruction of the spatiotemporal transmission and demographic history of coxsackievirus B2.

Background: Studies regarding coxsackievirus (CV) tend to focus on epidemic outbreaks, an imbalanced topology is considered to be an indication of acute infection with partial cross-immunity. In enteroviruses, a clear understanding of the characteristics of tree topology, transmission, and its demographic dynamics in viral succession and circulation are essential for identifying prevalence trends in endemic pathogens such as coxsackievirus B2 (CV-B2). This study applied a novel Bayesian evolutionary approach to elucidate the phylodynamic characteristics of CV-B2.

Phylodynamic analysis of the canine distemper virus hemagglutinin gene.

Background: Canine distemper (CD) is one of the most contagious and lethal viral diseases in dogs. Despite the widespread use of vaccines, the prevalence of the CD virus (CDV) has increased at an alarming rate in recent years. In this phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral demographic trends, and effectiveness of vaccines for CDV.

Transmission and Demographic Dynamics of Coxsackievirus B1.

The infectious activity of coxsackievirus B1 (CV-B1) in Taiwan was high from 2008 to 2010, following an alarming increase in severe neonate disease in the United States (US). To examine the relationship between CV-B1 strains isolated in Taiwan and those from other parts of the world, we performed a phylodynamic study using VP1 and partial 3Dpol (414 nt) sequences from 22 strains of CV-B1 isolated in Taiwan (1989-2010) and compared them to sequences from strains isolated worldwide. Phylogenetic trees were constructed by neighbor-joining, maximum likelihood, and Bayesian Monte Carlo Markov Chain methods.

Discovery of pentacyclic triterpenoids as potential entry inhibitors of influenza viruses.

Entry inhibitors are of particular importance in current efforts to develop a new generation of anti-influenza virus drugs. Here we report certain pentacyclic triterpenes exhibiting conserved structure features and with in vitro anti-influenza virus activity comparable to and even higher than that of oseltamivir. Mechanistic studies indicated that these lead triterpenoids bind tightly to the viral envelope hemagglutinin (HA), disrupting the interaction of HA with the sialic acid receptor and thus the attachment of viruses to host cells.

Development of bivalent oleanane-type triterpenes as potent HCV entry inhibitors.

The development of entry inhibitors is an emerging approach to the prevention and reduction of HCV infection. Starting from echinocystic acid (EA), a μM HCV entry inhibitor, we have developed a series of bivalent oleanane-type triterpenes which, upon optimization of the length, rigidity and hydrophobicity of the linker, exert dramatically potent enhancement of inhibition with IC50 values extending into the nM level. This study establishes the importance of triterpene natural products as new leads in the development of potential HCV entry inhibitors.

Synthesis and anti-HCV entry activity studies of β-cyclodextrin-pentacyclic triterpene conjugates.

In our previous studies, oleanolic acid (OA) and echinocystic acid (EA), isolated from Dipsacus asperoides, were found to have anti-HCV entry properties. The major issue for members of this type of triterpene is their low water solubility. In this study, a series of new water-soluble triazole-bridged β-cyclodextrin (CD)-pentacyclic triterpene conjugates were synthesized via click chemistry.

Analysis of circulating cholesterol levels as a mediator of an association between ABO blood group and coronary heart disease.

Background: Non-O type of ABO blood group has been associated with a predisposition to coronary heart disease. It is thought that this association is partly mediated by increased cholesterol levels in non-O-type individuals. In this study, we sought to estimate the mediation effect size.

Accumulation of the mutations in basal core promoter of hepatitis B virus subgenotype C1 increase the risk of hepatocellular carcinoma in Southern China.

Unlabelled: Hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, HBV subgenotype C1 is the major subgenotype in Southern China. The aim of this study was to investigate whether there was the specific mutation patterns in HBV/C1 associated with Southern Chinese patients with HCC.

Development of oleanane-type triterpenes as a new class of HCV entry inhibitors.

Development of hepatitis C virus (HCV) entry inhibitors represents an emerging approach that satisfies a tandem mechanism for use with other inhibitors in a multifaceted cocktail. By screening Chinese herbal extracts, oleanolic acid (OA) was found to display weak potency to inhibit HCV entry with an IC50 of 10 μM. Chemical exploration of this triterpene compound revealed its pharmacophore requirement for blocking HCV entry, rings A, B, and E, are conserved while ring D is tolerant of some modifications.