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The protective immune response to heat shock protein 60 of Histoplasma capsulatum is mediated by a subset of V beta 8.1/8.2+ T cells.

Immunization with recombinant heat shock protein 60 (rHsp60) from Histoplasma capsulatum or a region of the protein designated fragment 3 (F3) confers protection from a subsequent challenge in mice. To determine the T cell repertoire involved in the response to Hsp60, T cell clones from C57BL/6 mice immunized with rHsp60 were generated and examined for Vbeta usage by flow cytometry and RT-PCR. Vbeta8.1/8.2(+) T cells were preferentially expanded; other clones bore Vbeta4, -6, or -11. When Vbeta8.1/8.2(+) cells were depleted in mice, Vbeta4(+) T cell clones were almost exclusively isolated. Mea

Relationships between the onset of pustulosis palmaris et plantaris, periodontitis and bacterial heat shock proteins.

Relationships between the onset of pustulosis palmaris et plantaris, periodontitis and heat shock proteins were studied by using enzyme-linked immunosorbent assay to examine levels of immunoglobulin G (IgG) against Escherichia coli GroEL, a recombinant DnaJ of Actinobacillus actinomycetemcomitans heat shock protein, a synthetic peptide made from the 180th to the 188th amino acids of Mycobacterium bovis BCG Hsp65, and a recombinant human Hsp60, in sera obtained from 43 pustulosis palmaris et plantaris patients judged to have chronic infectious diseases of the oral cavity. We found that the tite

[Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway].

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a

Comparative Natural History of Visual Function From Patients With Biallelic Variants in BBS1 and BBS10.

PURPOSE: The purpose of this study was to compare the natural history of visual function change in cohorts of patients affected with retinal degeneration due to biallelic variants in Bardet-Biedl syndrome genes: BBS1 and BBS10. METHODS: Patients were recruited from nine academic centers from six countries (Belgium, Canada, France, New Zealand, Switzerland, and the United States). Inclusion criteria were: (1) female or male patients with a clinical diagnosis of retinal dystrophy, (2) biallelic disease-causing variants in BBS1 or BBS10, and (3) measures of visual function for at least one visit

Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge.

The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV e

Proteomics-based identification of HSP60 as a tumor-associated antigen in early stage breast cancer and ductal carcinoma in situ.

The detection of autoantibodies in cancer patients has been shown to constitute an excellent tool for early diagnosis. Because breast cancer still lacks early diagnostic markers, we investigated novel tumor-associated antigens and related autoantibodies in sera from patients with early stage breast cancer compared to autoimmune disease, other cancers, and healthy volunteers, using a proteomics-based approach. Among the 26 protein antigens specifically recognized by early stage breast cancer sera, we focused on Heat Shock Protein 60 (HSP60). Using ELISA, we investigated the frequency of autoant

Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent.

Humanin (HN) was originally identified as an endogenous peptide that protects neuronal cells from apoptosis induced by various types of Alzheimer's disease-related insults. We have previously indicated that HN increases cellular ATP levels and speculated that this peptide may rescue energy-deficient cells in mitochondrial disorders. Here, we report, for the first time, increased HN expression in skeletal muscles from patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). HN was strongly positive in all ragged-red fibers (RRFs) and some non-RRFs, an

Intrahepatic mRNA expression of interferon-inducible antiviral genes in liver diseases: dsRNA-dependent protein kinase overexpression and RNase L inhibitor suppression in chronic hepatitis C.

As a part of the defense mechanism of the host to viral infection, interferons induce the transcription of several genes. These interferon-inducible genes contribute to the eradication of the viruses. Whereas some studies suggested the participation of a dsRNA-dependent protein kinase in the host reaction to hepatitis C virus infection, the involvement of other interferon-inducible genes has not been evaluated. Furthermore, there has been no analysis on the expression profile of multiple interferon-inducible genes. The aim of this study was to clarify the hepatic mRNA expression profile of int

Developmental gene expression in the human fetal pancreas.

Differential developmental regulation of pancreas-specific genes has not been reported for the human fetal pancreas. We have therefore undertaken a systematic, quantitative analysis of the transcriptional levels of various genes in the human pancreas at different stages of fetal and postnatal development. Using sensitive ribonuclease protection assays, in situ hybridization, and the polymerase chain reaction, our results indicate the following: 1) Transcriptional levels of insulin and amylin remain lower in the fetal than in the adult pancreas, whereas glucagon and somatostatin mRNA levels are

Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.

Protein folding is a fundamental process ensuring that polypeptide chains acquire the correct three-dimensional structures required for biological function. This complex journey from nascent polypeptides to mature proteins is tightly regulated by the cellular proteostasis network-an integrated system of molecular chaperones, folding enzymes, and degradation machineries. Disruptions in this network lead to dysproteostasis, a pathological state implicated in a growing list of human diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. In this review, we provide a comp

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… Mitochondrial protein folding-HSP60/HSP10 chaperonin machinery After translocation into the matrix, many precursors achieve their native conformation inside the HSP60/HSP10 chaperonin cage (Fig. 2 ). … Unlike Group I chaperonins, which require a separate co-chaperonin (such as HSP10 in mitochondria), Group II chaperonins possess an intrinsic lid mechanism that facilitates protein folding without the need for an external co-chaperonin. 129 This intrinsic lid is formed by helical protrusions that cover …

Heterogeneity among Mycobacterium avium complex species isolated from pulmonary infection in Taiwan.

Mycobacterium avium complex (MAC) is an emerging pathogen causing nontuberculous pulmonary infections globally. However, clinical treatment guidelines regard MAC as a single entity, recommending a universal anti-mycobacterial combination therapy. Our study aimed to distinguish species among MAC and investigate the antimicrobial susceptibility for the selection of optimal antimicrobial agents in Taiwan. Two hundred ninety-four consecutive sputum samples confirmed as MAC by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were collected from 1 November 2015 to 31 Augu

Apparent but unconfirmed digenism in an Iranian consanguineous family with syndromic Retinal Disease.

BACKGROUND: Bardet-Biedl syndrome is an autosomal recessive disease characterized by rod-cone dystrophy, postaxial polydactyly, kidney defects, obesity, mental retardation and hypogonadism. Here, we report different genotypes in two Bardet-Biedl syndrome affected sisters with a different clinical phenotype regarding severity. MATERIALS AND METHODS: The proband of the family was examined by Next Generation Sequencing (NGS) using clinical exome and filtering by syndromic and non-syndromic genes associated with retinal dystrophies. RESULTS: Targeted NGS revealed two novel variants in the MKKS a

Long-Term Efficacy and Safety of Immunomodulatory Therapy for Atherosclerosis.

BACKGROUND AND AIMS: The long-term effect of immune tolerance has not been explored so far in atherosclerosis. In the present study, we assessed the effect of mucosal tolerance to a multi antigenic construct expressing three peptides from ApoB, HSP60, and outer membrane protein from Chlamydia pneumonia (AHC) for 30 weeks at every 6-week interval to understand the kinetics of immune modulation in disease progression. The safety profile of the molecule was also evaluated in mice. METHODS: Apobtm2SgyLdlrtm1Her/J mice (5-6 weeks) were orally dosed with multi antigenic construct (AHC) molecule on

Enterobacter cloacae Complex Isolates Harboring blaNMC-A or blaIMI-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids.

Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A blaNMC-A or blaIMI-type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapene

Expression profile of heat shock proteins in placental tissues of patients with preterm prelabor rupture of membranes and spontaneous preterm labor with intact membranes.

PROBLEM: Investigating the stress response in the central cotyledon zone of placental tissue in pregnancies with PPROM, PTB, and at term in labor. METHOD OF STUDY: Gene expression of Hsp27, Hsp60, Hsp70, Hsp90, and HspBP1 was compared between these particular groups. Correlation between variables including Hsp gene expression in placental tissue and the gestational age at delivery, WBC count at admission, and serum levels of CRP at admission in patients with PPROM and PTB was determined. RESULTS: Both PPROM and PTB pregnancies were associated with altered Hsp gene expression profile. While P

Diagnosing Chlamydia Trachomatis Urinary Tract Infections--Preliminary Report.

BACKGROUND: Chlamydia trachomatis is mentioned among the etiologic factors for urinary tract infections. Chlamydias are parasites inside a cell. A very significant problem of C. trachomatis infections is their asymptomatic character. The most frequent infections caused by these bacteria are inflammations of the urethra and bladder; of the vagina, cervix, vaginal cavity and adnexa in women; and of the epididymis, testicles and prostate in men. In the diagnosis of C. trachomatis infections, the following methods are used: immunofluorescent techniques, immunoenzymatic assays, serological examinat

Mycobacterium tuberculosis epitope-specific interferon-g production in healthy Brazilians reactive and non-reactive to tuberculin skin test.

The interferon (IFN)-γ response to peptides can be a useful diagnostic marker of Mycobacterium tuberculosis (MTB) latent infection. We identified promiscuous and potentially protective CD4+ T-cell epitopes from the most conserved regions of MTB antigenic proteins by scanning the MTB antigenic proteins GroEL2, phosphate-binding protein 1 precursor and 19 kDa antigen with the TEPITOPE algorithm. Seven peptide sequences predicted to bind to multiple human leukocyte antigen (HLA)-DR molecules were synthesised and tested with IFN-γ enzyme-linked immunospot (ELISPOT) assays using peripheral blood mo

Expression and regulation of toll-like receptors (TLRs) in human intervertebral disc cells.

PURPOSE: Although inflammatory processes play an essential role in painful intervertebral disc (IVD) degeneration, the underlying regulatory mechanisms are not well understood. This study was designed to investigate the expression, regulation and importance of specific toll-like receptors (TLRs)--which have been shown to play an essential role e.g. in osteoarthritis--during degenerative disc disease. METHODS: The expression of TLRs in human IVDs was measured in isolated cells as well as in normal or degenerated IVD tissue. The role of IL-1β or TNF-α in regulating TLRs (expression/activation)

IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis.

INTRODUCTION: Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60), recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G (IgG) subc

Oxidative inhibition of Hsp90 disrupts the super-chaperone complex and attenuates pancreatic adenocarcinoma in vitro and in vivo.

Pancreatic cancer is almost always fatal, in part because of its delayed diagnosis, poor prognosis, rapid progression and chemoresistance. Oncogenic proteins are stabilized by the Hsp90, making it a potential therapeutic target. We investigated the oxidative stress-mediated dysfunction of Hsp90 and the hindrance of its chaperonic activity by a carbazole alkaloid, mahanine, as a strategic therapeutic in pancreatic cancer. Mahanine exhibited antiproliferative activity against several pancreatic cancer cell lines through apoptosis. It induced early accumulation of reactive oxygen species (ROS) le