Calumenin, a Ca Binding Protein, Is Required for Dauer Formation in .

can adapt and survive in dynamically changing environments by the smart and delicate switching of molecular plasticity. dauer diapause is a form of phenotypic and developmental plasticity that induces reversible developmental arrest upon environmental cues. An ER (endoplasmic reticulum)-resident Ca binding protein, calumenin has been reported to function in a variety of malignant diseases in vertebrates and in the process of muscle contraction-relaxation.

BAM15 Relieves Neurodegeneration in Aged and Extends Lifespan.

BAM15 was recently screened as a protonophore uncoupler specifically for the mitochondrial membrane but not the plasma membrane. It is equally as potent as FCCP, but less toxic. Previously, mitochondrial uncoupling via DNP alleviates neurodegeneration in the nematode during aging.

Prediction and Feature Importance Analysis for Severity of COVID-19 in South Korea Using Artificial Intelligence: Model Development and Validation.

Background: The number of deaths from COVID-19 continues to surge worldwide. In particular, if a patient's condition is sufficiently severe to require invasive ventilation, it is more likely to lead to death than to recovery.

Objective: The goal of our study was to analyze the factors related to COVID-19 severity in patients and to develop an artificial intelligence (AI) model to predict the severity of COVID-19 at an early stage.

Flavonoids mitigate neurodegeneration in aged by mitochondrial uncoupling.

Dietary supplementation of flavonoids has been shown to reduce the severity of neurodegenerative disorders such as dementia, Parkinson's disease, and Alzheimer's disease by their antioxidant effects. However, their low bioavailability raises the question of how much their antioxidant capacity actually contributes to the mitigating effects. The physicochemical properties of flavonoids suggest they could function as mitochondrial uncouplers.

Novel Findings of Anti-Filarial Drug Target and Structure-Based Virtual Screening for Drug Discovery.

Lymphatic filariasis and onchocerciasis caused by filarial nematodes are important diseases leading to considerable morbidity throughout tropical countries. Diethylcarbamazine (DEC), albendazole (ALB), and ivermectin (IVM) used in massive drug administration are not highly effective in killing the long-lived adult worms, and there is demand for the development of novel macrofilaricidal drugs affecting new molecular targets. A Ca binding protein, calumenin, was identified as a novel and nematode-specific drug target for filariasis, due to its involvement in fertility and cuticle development in nematodes.

Mitochondrial Uncoupling Attenuates Age-Dependent Neurodegeneration in C. elegans.

The uncoupling protein 4 (ucp-4) gene is involved in age-dependent neurodegeneration in C. elegans. Therefore, we aimed to investigate the mechanism underlying the association between mitochondrial uncoupling and neurodegeneration by examining the effects of uncoupling agents and ucp-4 overexpression in C.

A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology.

Rapid diagnostic tests (RDTs) can detect anti-malaria antibodies in human blood. As they can detect parasite infection at the low parasite density, they are useful in endemic areas where light infection and/or re-infection of parasites are common. Thus, malaria antibody tests can be used for screening bloods in blood banks to prevent transfusion-transmitted malaria (TTM), an emerging problem in malaria endemic areas.

Enhanced performance of an innovative dengue IgG/IgM rapid diagnostic test using an anti-dengue EDI monoclonal antibody and dengue virus antigen.

High levels of anti-dengue IgM or IgG can be detected using numerous rapid diagnostic tests (RDTs). However, the sensitivity and specificity of these tests are reduced by changes in envelope glycoprotein antigenicity that inevitably occur in limited expression systems. A novel RDT was designed to enhance diagnostic sensitivity.

Development and clinical evaluation of a highly accurate dengue NS1 rapid test: from the preparation of a soluble NS1 antigen to the construction of an RDT.

Early diagnosis of dengue virus (DENV) is important. There are numerous products on the market claiming to detect DENV NS1, but these are not always reliable. In this study, a highly sensitive and accurate rapid diagnostic test (RDT) was developed using anti-dengue NS1 monoclonal antibodies.

Clinical diagnosis of early dengue infection by novel one-step multiplex real-time RT-PCR targeting NS1 gene.

Background: Dengue is a mosquito-borne disease that causes a public health problem in tropical and subtropical countries. Current immunological diagnostics based on IgM and/or nonstructural protein 1 (NS1) antigen are limited for acute dengue infection due to low sensitivity and accuracy.

Objectives: This study aimed to develop a one-step multiplex real-time RT-PCR assay showing higher sensitivity and accuracy than previous approaches.

6-trifluoromethyl-2-thiouracil possesses anti-Toxoplasma gondii effect in vitro and in vivo with low hepatotoxicity.

Since pyrimethamine, the general therapeutic drug for toxoplasmosis, presents several adverse side effects, the need to develop and evaluate new drugs for the condition is critical. In this study, anti-Toxoplasma gondii activities of 3-[{2-((E)-furan-2-ylmethylene)hydrazinyl}methylene]-1,3-dihydroindol-2-one (ATT-5126) and 6-trifluoromethyl-2-thiouracil (KH-0562) were evaluated in vitro using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and in vivo by measuring amount of the tachyzoites in mice ascites. Biochemical parameters such as lipid peroxidation (LPO), glutathione (GSH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were also evaluated in livers of mice at 4 days post-infection.

Evaluation of anti-coccidial effects of 1-[4-(4-nitrophenoxy)phenyl]propane-1-one and identification of its potential target proteins in Toxoplasma gondii.

Coccidiosis affects many vertebrates worldwide, but treatment with known anti-coccidial drugs causes several adverse side effects. There is a critical need for the development and evaluation of new drugs. The anti-coccidial effect of 1-[4-(4-nitrophenoxy)phenyl]propane-1-one (NPPP), a synthetic compound, was studied in vitro and in vivo.

Identification of active Plasmodium falciparum calpain to establish screening system for Pf-calpain-based drug development.

Background: With the increasing resistance of malaria parasites to available drugs, there is an urgent demand to develop new anti-malarial drugs. Calpain inhibitor, ALLN, is proposed to inhibit parasite proliferation by suppressing haemoglobin degradation. This provides Plasmodium calpain as a potential target for drug development.

Anti-malarial activity of new N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN) derivatives against Plasmodium falciparum.

Malaria is the most common of the parasitic diseases in tropical and subtropical regions. Adverse side effects of anti-malarial drugs have precluded them as a potential clinical drug. In this study, novel derivatives of N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN) based on a variety of dipeptidyl α,β-unsaturated amides containing lysine as a part were synthesized and evaluated.

Polymeric LabChip real-time PCR as a point-of-care-potential diagnostic tool for rapid detection of influenza A/H1N1 virus in human clinical specimens.

It is clinically important to be able to detect influenza A/H1N1 virus using a fast, portable, and accurate system that has high specificity and sensitivity. To achieve this goal, it is necessary to develop a highly specific primer set that recognizes only influenza A viral genes and a rapid real-time PCR system that can detect even a single copy of the viral gene. In this study, we developed and validated a novel fluidic chip-type real-time PCR (LabChip real-time PCR) system that is sensitive and specific for the detection of influenza A/H1N1, including the pandemic influenza strain A/H1N1 of 2009.

Development of a novel fluorophore for real-time biomonitoring system.

Rapid in-field diagnosis is very important to prevent the outbreak of various infectious and contagious diseases. Highly sensitive and quantitative detection of diseases can be performed using fluorescent immunochemical assay with specific antigen-antibody binding and a good quality fluorophore. This can lead to the development of a small, portable, quantitative biosensor to transmit diagnostic results to a control center in order to systematically prevent disease outbreaks.

Ethyl gallate induces apoptosis of HL-60 cells by promoting the expression of caspases-8, -9, -3, apoptosis-inducing factor and endonuclease G.

Many phytochemicals have been recognized to have potential therapeutic efficacy in cancer treatment. In this study, we investigated ethyl gallate (EG) for possible proapoptotic effects in the human promyelocytic leukemia cell line, HL-60. We examined cell viability, morphological changes, DNA content and fragmentation, and expression of apoptosis-related proteins for up to 48 h after EG treatment.

Production of monoclonal antibodies for Plasmodium vivax lactate dehydrogenase and patient sera screening using sandwich ELISA.

Malaria is a worldwide infectious disease. There are many diagnostic kits to detect malaria infection. However, the sensitivity of these diagnostic kits remains a problem.

Synthesis and evaluation of peptidyl α,β-unsaturated carbonyl derivatives as anti-malarial calpain inhibitors.

Malarial calpain is a cysteine protease believed to be a central mediator essential for parasitic activities. N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN), a calpain inhibitor, showed an excellent inhibitory effect on the erythrocytic stages of Plasmodium falciparum. However the aldehyde group of ALLN makes it susceptible to metabolism.

Simple and efficient model systems of screening anti-Toxoplasma drugs in vitro.

Introduction: A lot of in vitro technologies have been developed to screen drugs for toxoplasmosis, which is caused by Toxoplasma gondii and is one of the most serious infectious diseases in the world. However, developed screening methods still have limitation such as inaccuracy, labor-intensive and time-consuming procedure. Therefore, the development of simpler, more efficient and accurate high-throughput screening assay is needed.

Expression of exogenous human hepatic nuclear factor-1α by a lentiviral vector and its interactions with Plasmodium falciparum subtilisin-like protease 2.

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-1α is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions.

CNP-1 (ARRD-17), a novel substrate of calcineurin, is critical for modulation of egg-laying and locomotion in response to food and lysine sensation in Caenorhabditis elegans.

Calcineurin is a Ca(2+)/calmodulin-dependent protein phosphatase involved in calcium signaling pathways. In Caenorhabditis elegans, the loss of calcineurin activity causes pleiotropic defects including hyperadaptation of sensory neurons, hypersensation to thermal difference and hyper-egg-laying when worms are refed after starvation. In this study, we report on arrd-17 as calcineurin-interacting protein-1 (cnp-1), which is a novel molecular target of calcineurin.

The Methanol Extract of Azadirachta indica A. Juss Leaf Protects Mice Against Lethal Endotoxemia and Sepsis.

In the present study, the inhibitory effect of neem leaf extract (NLE) on lipopolysaccaride (LPS)-induced nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production was examined both in vitro and in vivo. In vitro study revealed that NLE treatment (100 μg/ml) inhibits LPS (100 ng/ml)-induced NO production by 96% and TNF-α production by 32%. The reduction in NO production is probably conferred by the complete suppression of inducible nitric oxide synthase (iNOS) expression.

DHS-21, a dicarbonyl/L-xylulose reductase (DCXR) ortholog, regulates longevity and reproduction in Caenorhabditis elegans.

Dicarbonyl/L-xylulose reductase (DCXR) converts l-xylulose into xylitol, and reduces various α-dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. In this study, we identified DHS-21 as the only DCXR ortholog in Caenorhabditis elegans. The dhs-21 gene is expressed in various tissues including the intestine, gonadal sheath cells, uterine seam (utse) cells, the spermathecal-uterus (sp-ut) valve and on the plasma membrane of spermatids.

Calcineurin may regulate multiple endocytic processes in C. elegans.

Calcineurin is a serine/threonine protein phosphatase controlled by Ca(2+) and calmodulin that has been implicated in various signaling pathways. Previously, we reported that calcineurin regulates coelomocyte endocytosis in Caenorhabditis elegans. So far, simple and powerful in vivo approaches have been developed to study various endocytic processes in C.