Advances in the Computational Identification of Allosteric Sites and Pathways in Proteins.

With the increasing difficulty to develop new drugs and the emergence of resistance to traditional orthosteric-site inhibitors, the search for alternatives is finally approaching the focus on allosteric sites. Allosteric sites offer opportunities to regulate many pharmacologically targeted pathways by inhibition or activation. In addition, allosteric sites tend to be less conserved than the functional site, which may facilitate the design of specific effectors in the protein families for which specific orthosteric inhibitors have proved difficult to design.

Rectovaginal Colonization With Pathogenic During Pregnancy And Neonatal Outcomes.

Purpose: The role of pathogenic colonization in asymptomatic pregnant women is not well understood. The purpose of this work was to determine the prevalence, antimicrobial susceptibility, and neonatal outcomes of pathogenic colonization in pregnant women.

Patients And Methods: A total of 137 women from southern Taiwan with singleton pregnancies were enrolled between March 2016 and June 2017.

GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways.

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far.

Natural phenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DPP IV) is a surface glycoprotein that can degrade glucagon like pepetide-1 (GLP-1) by decreasing blood sugar. Herbal medicines for diabetic therapy are widely used with acceptable efficacy but unsatisfied in advances. DPP IV was chosen as a template to employ molecular docking via Discovery Studio to search for natural phenolic compounds whether they have the inhibitory function of DPP IV.

The Exploration of Natural Compounds for Anti-Diabetes from Distinctive Species Garcinia with Comprehensive Review of the Garcinia Family.

Approximately 400 Garcinia species are distributed around the world. Previous studies have reported the extracts from bark, seed, fruits, peels, leaves, and stems of mangostana and that were used to treat adipogenesis, inflammation, obesity, cancer, cardiovascular diseases, and diabetes. Moreover, the hypoglycemic effects and underlined actions of different species such as G.

Binding site plasticity in viral PPxY Late domain recognition by the third WW domain of human NEDD4.

The recognition of PPxY viral Late domains by the third WW domain of the HECT-E3 ubiquitin ligase NEDD4 (hNEDD4-WW3) is essential for the completion of the budding process of numerous enveloped viruses, including Ebola, Marburg, HTLV1 or Rabies. hNEDD4-WW3 has been validated as a promising target for the development of novel host-oriented broad spectrum antivirals. Nonetheless, finding inhibitors with good properties as therapeutic agents remains a challenge since the key determinants of binding affinity and specificity are still poorly understood.

Tryptophan metabolite 5-methoxytryptophan ameliorates arterial denudation-induced intimal hyperplasia via opposing effects on vascular endothelial and smooth muscle cells.

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses.

Prolongs Survival in a Patient with Small Cell Lung Cancer.

: (AC) is an extremely rare medicinal fungus native to forested regions of Taiwan. It possesses numerous biological activities, especially anti-tumor effects shown in various in vitro cancer cells and in vivo animal models. However, there are few clinical reports about AC as a treatment for cancer patients.

The perceptions of natural compounds against dipeptidyl peptidase 4 in diabetes: from to .

Dipeptidyl peptidase IV (DPP-4), an incretin glucagon-like peptide-1 (GLP-1) degrading enzyme, contains two forms and it can exert various physiological functions particular in controlling blood glucose through the action of GLP-1. In diabetic use, the DPP-4 inhibitor can block the DDP-4 to attenuate GLP-1 degradation and prolong GLP-1 its action and sensitize insulin activity for the purpose of lowering blood glucose. Nonetheless the adverse effects of DPP-4 inhibitors severely hinder their clinical applications, and notably there is a clinical demand for novel DPP-4 inhibitors from various sources including chemical synthesis, herbs, and plants with fewer side effects.

Precision control of the large-scale green synthesis of biodegradable gold nanodandelions as potential radiotheranostics.

Herein, we report a new type of biodegradable, high surface-area gold nanodandelions (GNDs). This report possesses important features and some are the first of its kind: (1) the large scale green synthesis of GNDs with high monodispersity and a circa 100% yield with consistent chemistry, manufacturing and controls (CMC); (2) cellular/physiological degradability of GNDs leading to its disassembly into debris, which is indicative of the potential for possible body clearance; (3) precision control of the chemicophysical properties of the GNDs including shape, petal number and size, all can be judiciously fine-tuned by the synthetic parameters; (4) highly efficient radiotheranostics of GNDs encompassing better enhanced computed tomography (CT) contrast and pronounced X-ray induced reactive oxygen species (ROS) generation than conventional spherical gold nanoparticles (AuNP). It is noteworthy that the GNDs demonstrate a unique combinational effect of radiosensitization (production of superoxide anions and hydroxyl radicals) and type II photodynamic interaction (generation of singlet oxygen).

Double Monoubiquitination Modifies the Molecular Recognition Properties of p15 Promoting Binding to the Reader Module of Dnmt1.

The proliferating cell nuclear antigen (PCNA)-associated factor p15 is a nuclear protein that acts as a regulator of DNA repair during DNA replication. The p15 gene is overexpressed in several types of human cancer, and its function is regulated by monoubiquitination of two lysines (K15 and K24) at the protein N-terminal region. We have previously shown that p15 is an intrinsically disordered protein which partially folds upon binding to PCNA and independently contacts DNA through its N-terminal tail.

Homologous recombination defects and how they affect replication fork maintenance.

Homologous recombination (HR) repairs DNA double strand breaks (DSBs) and stabilizes replication forks (RFs). RAD51 is the recombinase for the HR pathway. To preserve genomic integrity, RAD51 forms a filament on the 3' end of a DSB and on a single-stranded DNA (ssDNA) gap.

Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence.

Traditional chemotherapy is being considered due to hindrances caused by systemic toxicity. Currently, the administration of multiple chemotherapeutic drugs with different biochemical/molecular targets, known as combination chemotherapy, has attained numerous benefits like efficacy enhancement and amelioration of adverse effects that has been broadly applied to various cancer types. Additionally, seeking natural-based alternatives with less toxicity has become more important.

An automatable platform for genotoxicity testing of nanomaterials based on the fluorometric γ-H2AX assay reveals no genotoxicity of properly surface-shielded cadmium-based quantum dots.

The large number of nanomaterial-based applications emerging in the materials and life sciences and the foreseeable increasing use of these materials require methods that evaluate and characterize the toxic potential of these nanomaterials to keep safety risks to people and environment as low as possible. As nanomaterial toxicity is influenced by a variety of parameters like size, shape, chemical composition, and surface chemistry, high throughput screening (HTS) platforms are recommended for assessing cytotoxicity. Such platforms are not yet available for genotoxicity testing.

Correction to: Variation in Blood and Colorectal Epithelia's Key Trace Elements along with Expression of Mismatch Repair Proteins from Localized and Metastatic Colorectal Cancer Patients.

The original version of this article unfortunately contained a mistake. The name of "Ali Ghorbani Ranjbary" is now corrected in the author group of this article. The original article has been corrected.

Functional diversification of sterol regulatory element binding proteins following gene duplication in a fungal species.

The sterol regulatory element binding proteins (SREBPs) are functionally well conserved and have been shown to regulate ergosterol synthesis in fungi. However, the distribution and evolution of the SREBPs in fungi, especially in the Pezizomycotina which comprised of a great many of animal and plant pathogens, are unexplored. In this study, we identified 641 SREBPs from 367 out of 530 fungi species.

Variation in Blood and Colorectal Epithelia's Key Trace Elements Along with Expression of Mismatch Repair Proteins from Localized and Metastatic Colorectal Cancer Patients.

Colorectal cancer (CRC) is an increasingly common medical issue affecting millions worldwide, and contribution of the body's trace elements to CRC is arguable. The concentrations and buffered status of selenium, iron, copper, zinc, and phosphorus in blood and large intestinal tissues of CRC patients are, respectively, variable and vital for cell physiology. The aim of this study was to assess selenium, iron, copper, zinc, and phosphorus variations in blood and colorectal epithelia along with examining the expression of mismatch repair proteins in CRC patients with/without metastasis for potential diagnosis/therapy.

Prevalence and risk factors for colonization by extended-spectrum β-lactamase-producing or ST 131 among asymptomatic adults in community settings in Southern Taiwan.

Fecal carriage of extended-spectrum β-lactamase-producing (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and -positive in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 have been published. From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium.

NIR optical carbon dioxide gas sensor based on simple azaBODIPY pH indicators.

Two simple boron-dipyrromethene-type fluorophore (azaBODIPYs) dyes are synthesized and tested for the determination of CO gas by an inner filter process. The indicators are noncovalently entrapped in suitable polymers according to their polarity, featuring absorption maxima at 620 nm and fluorescent emission maxima in the range 675-720 nm. Molar absorptivity and fluorescence quantum yield data were determined for these two synthesized azaBODIPYs.

Bloodstream infection with extended-spectrum beta-lactamase-producing Escherichia coli: The role of virulence genes.

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) strains hold the responsibility for the majority of E. coli infections. Numerous extraintestinal virulence factors (VFs) were possessed by ExPEC which are involved in the pathogenesis of infection.

Interactions of Alectinib with Human ATP-Binding Cassette Drug Efflux Transporters and Cytochrome P450 Biotransformation Enzymes: Effect on Pharmacokinetic Multidrug Resistance.

Alectinib is a tyrosine kinase inhibitor currently used as a first-line treatment of anaplastic lymphoma kinase-positive metastatic nonsmall cell lung cancer (NSCLC). In the present work, we investigated possible interactions of this novel drug with ATP-binding cassette (ABC) drug efflux transporters and cytochrome P450 (P450) biotransformation enzymes that play significant roles in the phenomenon of multidrug resistance (MDR) of cancer cells as well as in pharmacokinetic drug-drug interactions. Using accumulation studies in Madin-Darby canine kidney subtype 2 (MDCKII) cells alectinib was identified as an inhibitor of ABCB1 and ABCG2 but not of ABCC1.

Effects of Sting Plant Extracts as Penetration Enhancers on Transdermal Delivery of Hypoglycemic Compounds.

The percutaneous route is an interesting and inventive investigation field of drug delivery. However, it is challenging for drug molecules to pass through the skins surface, which is a characterized by its permeability barrier. The purpose of this study is to look at the effect of some penetration enhancers on in vivo permeation of insulin and insulin sensitizers (curcumin and rutin) through diabetes-induced mouse skin.

Seed Extracts Alleviated Blood Pressure in Phase I⁻Spontaneous Hypertension Rats.

Arterial pressure of each new breeding spontaneous Phase-1 hypertension (P1-HT) rat was recorded for 5 min by intravascular femoral artery catheter that served as a reference value prior to treatment. In the acute antihypertensive test, 0.36 g/kg Bwt of seed extract (PSE) was administered, via gavage feeding, to P1-HT rats, and the arterial pressures were continuously recorded for 1 h.