Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression

Mass spectrometry(MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes.The metabolomes of cells,tissues,and organisms comprise a variety of molecules including lipids,amino acids,sugars,organic acids,and so on.Metabolomics mainly focus on the hydrophilic classes,while lipidomics has emerged as an independent omics owing to the complexities of the organismal lipidomes.The potential roles of lipids and small metabolites in disease pathogenesis have been widely investigated in various human diseases,but system-level understanding is largely lacking,which could be partly attributed to the insufficiency in terms of metabolite coverage and quantitation accuracy in current analytical technologies.While scientists are continuously striving to develop high-coverage omics approaches,integration of metabolomics and lipidomics is becoming an emerging approach to mechanistic investigation.Integration of metabolome and lipidome offers a complete atlas of the metabolic landscape,enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology,facilitating the study of interconnection between lipids and other metabolites in disease progression.In this review,we summarize omics-based findings on the roles of lipids and metabolites in the pathogenesis of selected major diseases threatening public health.We also discuss the advantages of integrating lipidomics and metabolomics for in-depth understanding of molecular mechanism in disease pathogenesis.     

WNK1： analysis of protein kinase structure, downstream targets, and potential roles in hypertension

The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis, lntronic deletions in the WNK1 gene resuk in its overexpression and lead to pseudohypoaldosteronism type Ⅱ, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.     

A case-control study of risk factors for severe hand-foot-mouth disease in Yuxi,China, 2010–2012

正Dear Editor,Here,we report the risk factors for severe hand-foot-mouth disease(HFMD)determined by our case-controlstudy.Our findings could help disease prevention and in-tervention initiatives.Patients with severe HFMD displayfatal clinical manifestations with sequelae,requiring≥7days of hospitalization.A tota1 of 249 severe cases treat-ed at Yuxi Children’s Hospital were included in the case     

Call for Papers Special Issue on “Biomarkers for Diseases”

正The journal Genomics ProteomicsBioinformatics(GPB)is now inviting submissions for a special issue(to be published in June of 2015)on the topic of"Biomarkers for Diseases".As an emerging index,disease biomarkers have demonstrated the potential application in diagnosis and prognosis.The detection of the disease indicators at molecular level,DNA,RNA,protein or metabolites,could gain highly     

Poly-β-hydroxybutyrate alleviated diarrhea and colitis via Lactobacillus johnsonii biofilm-mediated maturation of sulfomucin

Maintainance of sulfomucin is a key end point in the treatment of diarrhea and inflammatory bowel disease(IBD). However, the mechanisms underlying the microbial sense to sulfomucin are poorly understood, and to date, there are no therapies targeting the secretion and maturation of sulfomucin in IBD. Herein, we biosynthesized poly-β-hydroxybutyrate(PHB) and found that PHB could alleviate inflammation caused by diarrhea and colitis by enhancing the differentiation of sulfomucin. Microbiota transpl...     

Understanding the importance of autophagy in human diseases using Drosophila

Autophagy is a lysosome-dependent intracellular degradation pathway that has been implicated in the pathogenesis of various human diseases, either positively or negatively impacting disease outcomes depending on the specific context. The majority of medical conditions including cancer, neurodegenerative diseases, infections and immune system disorders and inflammatory bowel disease could probably benefit from therapeutic modulation of the autophagy machinery. Drosophila represents an excellent model animal to study disease mechanisms thanks to its sophisticated genetic toolkit, and the conservation of human disease genes and autophagic processes. Here, we provide an overview of the various autophagy pathways observed both in flies and human cells(macroautophagy, microautophagy and chaperone-mediated autophagy), and discuss Drosophila models of the above-mentioned diseases where fly research has already helped to understand how defects in autophagy genes and pathways contribute to the relevant pathomechanisms.     

Special Issue on ‘‘Biomarkers for Diseases”

<正>The journal Genomics ProteomicsBioinformatics(GPB)is now inviting submissions for a special issue(to be published in the winter of 2015)on the topic of‘‘Biomarkers for Diseases’’.As an emerging index,disease biomarkers have demonstrated the potential application in diagnosis and prognosis.The detection of the disease indicators at molecular level,DNA,RNA,protein or metabolites,could gain highly sensitive and specific signals that truly reflect     

Amelioration of β^654-thalassemia in mouse model with the knockdown of aberrantly spliced β-globin mRNA

Large amounts of aberrantly spliced mRNA from the β654 allele was present in erythroid cells, which might impair the erythropoiesis.A therapeutic strategy for β-thalassemia was explored by knocking down the aberrantly spliced mRNA of β-globin. Lentiviral vector with siRNA fragment targets on the specific portion of β654-globin aberrantly spliced pre-mRNA was constructed. In HeLa β654 cells, the siRNA vector could reduce approximately 60% of aberrantly spliced mRNA, which was assessed by RT-PCR and qRT-PCR. Furthermore, a disease model of β654 thalassemia mice with lentiviral-mediated siRNA was produced by subzonal injection (named Hβi-Hbbth-4/Hbb+transgenic mice). Our results showed that the hemotological parameters were improved in Hβi-Hbbth-4/Hbb+ transgenic mice. This study provides a potential way for β654-thalassemia therapy by knocking down the aberrantly spliced β-globin mRNA, whilst supporting that the aberrantly spliced β-globin mRNA may aggravate the disease.     

Synergic effects of NO and oxygen free radicals in the injury of ischemia-reperfused myocardium——ESR studies on NO free radicals generated from ischemia-reperfused myocardium

The ESR signal of NO bound to hemoglobin was detected during the ischemia-reperfusion of myocardium with low temperature ESR technique, and the synergic effects of NO and oxygen free radicals in the injury of the process were studied with this technique. Oxygen free radicals and NO bound to β-subunit of hemoglobin (β-NO complex) could be detected simultaneously in the ischemia-reperfused myocardium. Those signals could not be detected from the normal myocardium even in the presence of L-arginme. However, those signals could be detected and were dose-dependent with L-arginine in the ischemia-reperfused myocardiums and the signal could be suppressed with the inhibitor of NO synthetase, NG-nitro-L-arginine methylester (NAME). Measurement of the activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary artery effluent of ischemia-reperfused heart showed that L-arginine at lower concentration (<1 mmol/L) could protect the heart from the ischemia-reperfusion injury but at higher con     

Role of chaperone-mediated autophagy in degrading Huntington＇s disease-associated huntingtin protein

Mutant N-terminal huntingtin （Htt） protein resulting from Huntington＇s disease （HD） with expanded polyglutamine accumulates and forms aggregates in vulnerable neurons. Both ubiquitin proteasomai and autophagic pathways con- tribute to the degradation of mutant Htt. Here, we focus on the involvement of chaperone-mediated autophagy （CMA）, a selective form of autophagy in the clearance of Htt. Selective catabolism in CMA is conferred by the presence of a KFERQ-Iike targeting motif in the substrates, by which molecular chaperones recognize the hydrophobic surfaces of the misfolded substrates, and transfer them to the lysosomal membrane protein type-2A, LAMP-2A. The substrates are taken into the lysosomes through LAMP-2A and are rapidly degraded by the lysosomal enzymes. Taken together, we summarize the recent evidence to elucidate that Htt is also a potential substrate of CMA. We propose that the manipulation of CMA could be a therapeutic strat- egy for HD.     

Biomarkers of Alzheimer’s disease in body fluids

Various innovative diagnostic methods for Alzheimer’s disease (AD) have been developed in view of the increasing preva-lence and consequences of later-life dementia. Biomarkers in cerebrospinal fluid (CSF) and blood for AD are primarily based on the detection of components derived from amyloid plaques and neurofibrillary tangles (NFTs). Published reports on CSF and blood biomarkers in AD indicate that although biomarkers in body fluids may be utilized in the clinical diagnosis of AD, there are no specific markers that permit accurate and reliable diagnosis of early-stage AD or the monitoring of disease pro-gression.     

Keratin expression during early embryonic development of Bufo bufo gargarizans

Three anti-keratin MAbs were used to identify keratins expressed in early embryos of Bufo bufo gargarizans .MAb AF5 recognized three polypeptides of keratin in oocytes,fertilized egge up to neurula stage three other keratins(62,58and 54Kd) began to express and could be detected by AF5,MAbs D10 and K12 gave different results both of them could identify four keratinlike molecules with unusual molecular weights(Mr 98,95,30and 27K),Moreover,D10 could also detect a 54 Kd keratin in neurula and taibud stage embryos while K12 could reveal,beside 54Kd keratin,Other four more keratins(68,65,62 and 60Kd).The possible interpretion of these results and their implications are discussed.     

A Recombinant Rabies Virus Expressing Fms-like Tyrosine Kinase 3 Ligand (Flt3L) Induces Enhanced Immunogenicity in Mice

Rabies is a zoonotic disease that still causes 59,000 human deaths each year, and rabies vaccine is the most effective way to control the disease. Our previous studies suggested that the maturation of DC plays an important role in enhancing the immunogenicity of rabies vaccine. Flt3 L has been reported to own the ability to accelerate the DC maturation, therefore, in this study, a recombinant rabies virus expressing mouse Flt3 L, designated as LBNSE-Flt3 L, was constructed, and its immunogenicity was characterized. It was found that LBNSE-Flt3 L could enhance the maturation of DC both in vitro and in vivo, and significantly more TFHcells and Germinal Center B(GC B) cells were generated in mice immunized with LBNSE-Flt3 L than those immunized with the parent virus LBNSE. Consequently, expressing of Flt3 L could elevate the level of virus-neutralizing antibodies(VNA) in immunized mice which provides a better protection from a lethal rabies virus challenge. Taken together, our study extends the potential of Flt3 L as a good adjuvant to develop novel rabies vaccine by enhancing the VNA production through activating the DC–TFH–GC B axis in immunized mice.     

Mechanisms of autophagy and apoptosis: Recent developments in breast cancer cells

Autophagy,the pathway whereby cell components are degraded by lysosomes,is involved in the cell response to environmental stresses,such as nutrient deprivation,hypoxia or exposition to chemotherapeutic agents.Under these conditions,which are reminiscent of certain phases of tumor development,autophagy either promotes cell survival or induces cell death. This strengthens the possibility that autophagy could be an important target in cancer therapy,as has been proposed.Here,we describe the regulation of survival and death by autophagy and apoptosis,especially in cultured breast cancer cells.In particular,we discuss whether autophagy represents an apoptosis-independent process and/or if they share common pathways. We believe that understanding in detail the molecular mechanisms that underlie the relationships between autophagy and apoptosis in breast cancer cells could improve the available treatments for this disease.     

Special Issue on ＂Biomarkers for Diseases＂

The journal Genomics Proteomics ＆ Bioinformatics （GPB） is now inviting submissions for a special issue （to be published in June of 2015） on the topic of ＂Biomarkers for Diseases＂.
As an emerging index, disease biomarkers have demonstrated the potential application in diagnosis and prognosis. The detection of the disease indicators at molecular level, DNA, RNA, protein or metabolites, could gain highly sensitive and specific signals that truly reflect the pathological changes and fully facilitate diagnostic analysis at early phase with invasive mode. Revolution of high-throughput techniques, such as genome-sequencing and mass spectrometers, greatly promotes the discovery and application of the disease biomarkers. The existing disease biomarkers have covered nearly all the macromolecular categories as well as their variants and modifications, including predisposing genetic variations （such as SNPs）, mutations, epigenetic modifications, miRNAs, splice isoforms, abnormal proteins and autoantibodies. Although some biomarkers have been adopted in clinical practice, there are still great needs for studies on identifying new ones, understanding the existing ones and applying the well-studied ones in practice.     

MDV-1 VP22 conjugated VP2 enhancing immune response against infectious bursal disease virus by DNA vaccination in mice

VP22 of Marek’s disease virus serotype 1 (MDV-1) could function in protein transduction. In this study, an infectious bursal disease virus VP2 gene was fused to the carboxyl termini of VP22. It showed that the fusion protein did not spread into the bystander cells from the cells transfected with pVP22-VP2, as the VP22 alone could. The VP22 proteins were found to be translocated into all the nuclei in the neighboring COS-1 cells, as analyzed by a fluorescence assay. Although mice were immunized with the recombinant DNAs mixed with polyethylenimine (PEI) at a dose of 1:2, it failed to enhance the antibody response against IBDV VP2, as measured by the indirect ELISA assay, yet the cell mediated immune response was significantly increased. The ratio of CD8 /CD4 T cells was significantly increased in the immunized group with the fusion genes, compared with the group immunized with VP2 (P<0.05). Our results demonstrated that VP22 indeed enhances the cell-mediated response in the fused VP2 in a mice model system, possibly due to the fact that the IBDV VP2 could be carried into the surrounding cells at a limited level under pressure from MDV VP22.     

Frequency and Absolute Number of FoxP3^＋ Regulatory T Cells Correlate with Disease Progression of Chronic HIV-1 Infection

CD4 CD25 Regulatory T cells (Treg) have been found to down-regulate immune activation in HIV-1 infection. However,whether the depletion of Treg benefits to the disease status of HIV infection remains undefined. To address this issue,we enumerated the Treg absolute counts and frequency in 75 antiviral-nave HIV-1-infected individuals in this study. It was found that HIV-infected patients displayed a significant decline in Treg absolute counts but a significant increase in Treg frequency. In addition,with disease progression indicated by CD4 T-cell absolute counts,circulating Treg frequency gradually increased; while Treg absolute counts were gradually decreased,suggesting that the alteration of Treg number closely correlated with disease progression in HIV infection. Functional analysis further showed that Treg efficiently inhibit both CD4 and CD8 T cell proliferation in vitro. Thus,our findings indicates that Treg actively participate in pathogenesis of chronic HIV infection,influencing the disease progression.     

Biomarkers of neurodegenerative disorders： How good are they？

Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies,biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differentiable between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance,are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated β-amyloid peptide for Alzheimer‘s disease (AD), α-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson‘s disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington‘s gene mutations in Huntington‘s disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.     

Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia

Aplastic anemia(AA) is a life-threatening disease characterized by bone marrow(BM) failure and pancytopenia. As an important component of the BM microenvironment, endothelial cells(ECs) play a crucial role in supporting hematopoiesis and regulating immunity. However, whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown. In this study, a classical AA mouse model and VE-cadherin blocking antibod...