anti-HSP70 Antibody Research Articles

A longitudinal assessment of heat exposure and biomarkers of kidney function on heat shock protein 70 and antibodies among agricultural workers

BackgroundExposure to extreme heat impacts millions of people worldwide and outdoor workers are among the populations most affected by hot temperatures. Heat stress induces several biological responses in humans, including the production of heat shock proteins (HSP) and antibodies against HSP (anti-HSP) which may play a central role in the body’s cellular response to a hot environment.ObjectiveThis longitudinal study investigated the impact of elevated temperatures and humidity on the presence of HSP70 and anti-HSP70 and examined relationships with markers of kidney function in an at-risk workforce under conditions of extreme heat and exertion in Guatemala.MethodsWe collected ambient temperature and relative humidity data as well as biomarkers and clinical data from 40 sugarcane workers at the start and the end of a 6-month harvest. We used generalized mixed-effects models to estimate temperature effects on HSP70 and anti-HSP70 levels. In addition, we examined trends between HSP70 and anti-HSP70 levels and markers of kidney function across the harvest.ResultsAt the end of the harvest, temperatures were higher, and workers had, on average, higher levels of HSP70 and anti-HSP70 compared to the beginning of the season. We observed significant increasing trends with temperature indices, heat index, and HSP70 levels. Maximum temperature was associated with HSP70 increments after controlling for age, systolic and diastolic blood pressure (β: 0.21, 95% Confidence Interval: 0.09, 0.33). Kidney function decline across the harvest was associated with both higher levels of anti-HSP70 levels at the end of the harvest as well as greater increases in anti-HSP70 levels across the harvest.ConclusionsThese results suggest that workplace heat exposure may increase the production of HSP70 and anti-HSP70 levels and that there may be a relationship between increasing anti-HSP70 antibodies and the development of renal injury. HSP70 holds promise as a biomarker of heat stress in exposed populations.

Pathogenic Autoimmunity in Atherosclerosis Evolves from HSP60-Reactive CD4 + T Cells.

Clinical evidence suggests anti-Hsp60 antibodies could contribute to atherosclerosis (AS) development, with unclear mechanisms. This study aims to explore the role of anti-HSP60-mediated autoimmunity in AS progression. HSP60-MHC tetramers were used to characterize HSP60-specific CD4 + T cells and assess TCR responses in mice. These cells were transplanted into AS mice to examine immune cell differentiation and infiltration in plaques and blood. Mice were injected with recombinant HSP60 or anti-HSP60 sera to evaluate effects on plaque progression and macrophage activity. Experiments with muMT-/-Apoe-/- mice examined humoral immunity's role in this autoimmunity. HSP60-reactive CD4 + T cells in AS mice differentiated into follicular helper cells, not Th1/Th17. Anti-HSP60 treatments increased macrophage infiltration and M1 polarization, indicating an anti-HSP60-driven inflammatory progression, dependent on humoral immunity. Anti-HSP60 influences macrophage infiltration, polarization, and plaque formation via humoral immunity, shedding light on its potential role in AS progression.

Autoimmunity to stromal-derived autoantigens in rheumatoid ectopic germinal centers exacerbates arthritis and affects clinical response.

Ectopic lymphoid structures (ELSs) in the rheumatoid synovial joints sustain autoreactivity against locally expressed autoantigens. We recently identified recombinant monoclonal antibodies (RA-rmAbs) derived from single, locally differentiated rheumatoid arthritis (RA) synovial B cells, which specifically recognize fibroblast-like synoviocytes (FLSs). Here, we aimed to identify the specificity of FLS-derived autoantigens fueling local autoimmunity and the functional role of anti-FLS antibodies in promoting chronic inflammation. A subset of anti-FLS RA-rmAbs reacting with a 60 kDa band from FLS extracts demonstrated specificity for HSP60 and partial cross-reactivity to other stromal autoantigens (i.e., calreticulin/vimentin) but not to citrullinated fibrinogen. Anti-FLS RA-rmAbs, but not anti-neutrophil extracellular traps rmAbs, exhibited pathogenic properties in a mouse model of collagen-induced arthritis. In patients, anti-HSP60 antibodies were preferentially detected in RA versus osteoarthritis (OA) synovial fluid. Synovial HSPD1 and CALR gene expression analyzed using bulk RNA-Seq and GeoMx-DSP closely correlated with the lympho-myeloid RA pathotype, and HSP60 protein expression was predominantly observed around ELS. Moreover, we observed a significant reduction in synovial HSP60 gene expression followed B cell depletion with rituximab that was strongly associated with the treatment response. Overall, we report that synovial stromal-derived autoantigens are targeted by pathogenic autoantibodies and are associated with specific RA pathotypes, with potential value for patient stratification and as predictors of the response to B cell-depleting therapies.

Антитіла до білків теплового шоку людини та бактерій із молекулярною масою 60кДа при накладеній прееклампсії

Purpose - to measure the blood serum levels of anti-HSP60 and anti-GroEL antibodies in pregnant women with chronic hypertension and superimposed preeclampsia, to evaluate the prospects of using these indicators as superimposed preeclampsia predictors. Materials and methods. Prospective cohort observational study, which consisted of 105 pregnant women with chronic hypertension and the control group - 34 healthy pregnant women. Blood samples were collected at 28 weeks (first study point), the second time at 36 weeks in case of preeclampsia absence or at 29-35 weeks if preeclampsia added (second study point). If preeclampsia occurred after 36 weeks, additional anti-HSP60 and anti-GroEL antibodies measurements were not performed. Anti-HSP60 and anti-GroEL antibodies were measured by immunosorbent assay. Results. At 28 weeks anti-HSP60 and anti-GroEL antibodies growth was detected in the chronic hypertension and superimposed preeclampsia subgroups compared to the healthy subgroup (p<0.01 and p<0.001 respectively for anti-HSP60; p<0.0001 for anti-GroEL in both cases), no difference was found between chronic hypertension and superimposed preeclampsia subgroups. At the second study point, anti-HSP60 antibodies were increased in the chronic hypertension and superimposed preeclampsia subgroups compared to the healthy subgroup (p<0.01 and p<0.0001, respectively); a statistically significant difference was found between chronic hypertension and superimposed preeclampsia subgroups (p<0.01). Anti-GroEL antibodies at the second study point were increased in the chronic hypertension and superimposed preeclampsia subgroups compared to the healthy subgroup (p<0.001 and p<0.0001), however, no statistically significant difference was found between levels in the chronic hypertension and superimposed preeclampsia subgroups. Anti-HSP60 antibodies showed a strong correlation with anti-GroEL antibodies in all subgroups at the first study point, same was true for healthy and chronic hypertension subgroups at the second study point. There was no correlation between anti-HSP60 and anti-GroEL antibodies indicators in the superimposed preeclampsia subgroup at the second study point (p=0.059). There was no growth of anti-GroEL antibodies with gestational age increase in the chronic hypertension subgroup. Anti-HSP60 antibodies increase at the second study point compared to concentrations at 28 weeks in the chronic hypertension subgroup (p<0.001) and the superimposed preeclampsia subgroup (p<0.001). Conclusions. Loss of immunological tolerance to HSP60 and exacerbation of immunological reactivity against GroEL accompany hypertensive disorders course during pregnancy. Anti-HSP60 antibodies may play a more significant role in superimposed preeclampsia development. Application of anti-HSP60 and anti-GroEL antibodies as superimposed preeclampsia predictors needs further study. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Association between Genetic Variants Linked to Premature Ovarian Insufficiency and Inflammatory Markers: A Cross-Sectional Study.

Premature menopause (PM) is the cessation of ovarian function before age 40. PM women are more likely to have cardiovascular diseases (CVDs), diabetes, and mental disorders. This is the first study that assessed the association of single nucleotide polymorphisms (SNPs) with anti-heat shock protein 27 (Hsp27), High-sensitivity C-reactive protein (hs- CRP), and PM and serum pro-oxidant-antioxidant balance (PAB), as putative risk factors for CVDs. We aimed to explore the association of oxidative stress markers with eight different SNPs shown to be related to premature menopause. In this cross-sectional research, we included 183 healthy women and 117 premature menopausal women. We determined baseline characteristics for all participants and measured serum hs-CRP, anti-HSP-27 antibody titer, and PAB levels using the established methods. Genotyping for eight SNPs was done using the tetra amplification refractory mutation system polymerase chain reaction (Tetra-ARMS PCR) and allele-specific oligonucleotide PCR (ASO-PCR) methods. We found a significant difference between mean serum PAB levels and the genetic variant of rs16991615 (P=0.03). ANCOVA showed a significant effect of the genotypes rs4806660 and rs10183486 on hs-CRP serum levels in the case and control groups, respectively (P=0.04 and P=0.007). ANCOVA also showed an association between rs244715 genotypes and anti-hsp27 serum levels in the case group (P=0.02). There was a significant effect of the genotypes of rs451417 on the serum hs-CRP level in the control group (P=0.03). There was a significant association of the genetic variants related to PM with oxidative stress and inflammatory markers (serum PAB, anti-hsp27 antibody, and hs-CRP). Accordingly, this seems to be an effective approach to predicting susceptible subjects for cardiovascular and mental disorders as well as various cancers.

Ovarian cancer cells regulate their mitochondrial content and high mitochondrial content is associated with a poor prognosis

Most cancer patients ultimately die from the consequences of distant metastases. As metastasis formation consumes energy mitochondria play an important role during this process as they are the most important cellular organelle to synthesise the energy rich substrate ATP, which provides the necessary energy to enable distant metastasis formation. However, mitochondria are also important for the execution of apoptosis, a process which limits metastasis formation. We therefore wanted to investigate the mitochondrial content in ovarian cancer cells and link its presence to the patient’s prognosis in order to analyse which of the two opposing functions of mitochondria dominates during the malignant progression of ovarian cancer. Monoclonal antibodies directed against different mitochondrial specific proteins, namely heat shock proteins 60 (HSP60), fumarase and succinic dehydrogenase, were used in immunohistochemistry in preliminary experiments to identify the antibody most suited to detect mitochondria in ovarian cancer cells in clinical tissue samples. The clearest staining pattern, which even delineated individual mitochondria, was seen with the anti-HSP60 antibody, which was used for the subsequent clinical study staining primary ovarian cancers (n = 155), borderline tumours (n = 24) and recurrent ovarian cancers (n = 26). The staining results were semi-quantitatively scored into three groups according to their mitochondrial content: low (n = 26), intermediate (n = 50) and high (n = 84). Survival analysis showed that high mitochondrial content correlated with a statistically significant overall reduced survival rate In addition to the clinical tissue samples, mitochondrial content was analysed in ovarian cancer cells grown in vitro (cell lines: OVCAR8, SKOV3, OVCAR3 and COV644) and in vivo in severe combined immunodeficiency (SCID) mice.In in vivo grown SKOV3 and OVCAR8 cells, the number of mitochondria positive cells was markedly down-regulated compared to the in vitro grown cells indicating that mitochondrial number is subject to regulatory processes. As high mitochondrial content is associated with a poor prognosis, the provision of high energy substrates by the mitochondria seems to be more important for metastasis formation than the inhibition of apoptotic cell death, which is also mediated by mitochondria. In vivo and in vitro grown human ovarian cancer cells showed that the mitochondrial content is highly adaptable to the growth condition of the cancer cells.

Photodynamic Therapy Supported by Antitumor Lipids.

Photodynamic therapy (PDT) destroys tumors by generating cytotoxic oxidants that induce oxidative stress in targeted cancer cells. Antitumor lipids developed for cancer therapy act also by inflicting similar stress. The present study investigated whether tumor response to PDT can be improved by adjuvant treatment with such lipids using the prototype molecule edelfosine. Cellular stress intensity following Photofrin-based PDT, edelfosine treatment, or their combination was assessed by the expression of heat shock protein 70 (HSP70) on the surface of treated SCCVII tumor cells by FITC-conjugated anti-HSP70 antibody staining and flow cytometry. Surface HSP70 levels that became elevated after either PDT or edelfosine rose much higher after their combined treatment. The impact of Photofrin-PDT-plus-edelfosine treatment was studied with three types of tumor models grown in syngeneic mice. With both SCCVII squamous cell carcinomas and MCA205 fibrosarcoma, the greatest impact was with edelfosine peritumoral injection at 24 h after PDT, which substantially improved tumor cure rates. With Lewis lung carcinomas, edelfosine was highly effective in elevating PDT-mediated tumor cure rates even when injected peritumorally immediately after PDT. Edelfosine used before PDT was ineffective as adjuvant with all tumor models. The study findings provide proof-in-principle for use of cancer lipids with tumor PDT.

Extracellular Hsp70 Is Involved in the CXCL12/CXCR4 Pathway in Primary Human Nasal Epithelial Cells: A Preliminary Study

Background and Objectives: To date, no studies have been conducted on the interaction between extracellular heat shock protein 70 (Hsp70) and C-X-C chemokine receptor type 4 (CXCR4) in the upper airway. We aimed to evaluate the relationship between extracellular Hsp70 and CXCR4 and their role in the primary human nasal epithelium.Methods: We cultured primary human nasal epithelial (HNE) cells in an air–liquid interface. Macrogen performed single-cell quantitative polymerase chain reaction and sequencing. We conducted western blot analysis for the CXCR4 and mitogen-activated protein kinase (MAPK) pathways.Results: Extracellular Hsp70 treatment significantly increased the genetic expression and protein levels of CXCR4 in primary HNE cells. Phospho-ERK expression was increased by cotreatment with Hsp70 and CXCL12, but inhibited by pretreatment with AMD3100, a CXCR4 inhibitor. Pretreatment with an anti-Hsp70 antibody reduced phospho-ERK expression upregulation induced by cotreatment with Hsp70 and CXCL12.Conclusion: Extracellular Hsp70 participates in the activation of the CXCR4-dependent downstream signaling pathway in HNE cells. Further studies should evaluate the extracellular Hsp70-CXCL12/CXCR4 axis and the role of its components in the development of inflammatory diseases.

Prediction of serum anti-HSP27 antibody titers changes using a light gradient boosting machine (LightGBM) technique

Previous studies have proposed that heat shock proteins 27 (HSP27) and its anti-HSP27 antibody titers may play a crucial role in several diseases including cardiovascular disease. However, available studies has been used simple analytical methods. This study aimed to determine the factors that associate serum anti-HSP27 antibody titers using ensemble machine learning methods and to demonstrate the magnitude and direction of the predictors using PFI and SHAP methods. The study employed Python 3 to apply various machine learning models, including LightGBM, CatBoost, XGBoost, AdaBoost, SVR, MLP, and MLR. The best models were selected using model evaluation metrics during the K-Fold cross-validation strategy. The LightGBM model (with RMSE: 0.1900 ± 0.0124; MAE: 0.1471 ± 0.0044; MAPE: 0.8027 ± 0.064 as the mean ± sd) and the SHAP method revealed that several factors, including pro-oxidant-antioxidant balance (PAB), physical activity level (PAL), platelet distribution width, mid-upper arm circumference, systolic blood pressure, age, red cell distribution width, waist-to-hip ratio, neutrophils to lymphocytes ratio, platelet count, serum glucose, serum cholesterol, red blood cells were associated with anti-HSP27, respectively. The study found that PAB and PAL were strongly associated with serum anti-HSP27 antibody titers, indicating a direct and indirect relationship, respectively. These findings can help improve our understanding of the factors that determine anti-HSP27 antibody titers and their potential role in disease development.

Association Between Serum Levels of Anti-heat Shock Protein 27 Antibody and Liver Cell Injury in Chronic Hepatitis B.

Heat Shock Protein 27 (HSP27), an anti-HBV factor, exists in the intracellular and extracellular spaces. As an inflammatory modulator, serum HSP27 (sHSP27) is associated with elevated pro-inflammatory cytokines and a higher likelihood of hepatocellular carcinoma in chronic hepatitis. SHSP27 results in natural antibody production (anti-HSP27-Ab) that is more stable and easily detectable compared to sHSP27. We aimed to investigate any potential association between anti-HSP27-Ab level and chronic hepatitis B (CHB) progression and inflammation indicated by liver cell injury and HBV replication. This cross-sectional study was conducted on 91 patients with CHB and 92 individuals without CHB. Following demographic data collection, anti-HSP27-Ab, serum lipids including total cholesterol, triglyceride, LDL-C, HDL-C, and aminotransferase levels were measured using enzymatic assays in participants' serum samples. HBV DNA was also measured by quantitative PCR in CHB patients. Bivariate and multivariate analyses showed a significantly higher mean level of anti-HSP27-Ab in CHB than in healthy individuals (0.304 vs. 0.256AU/ml, P value = 0.015). These levels held significant differences in the CHB subgroups of male patients, at the age of 50years and above, with non-smoking status, elevated aminotransferase levels, and hypotriglyceridemia (P value < 0.05). However, no difference was found between the antibody levels and HBV DNA copies (P value > 0.05). This study provides evidence that anti-HSP27 antibody levels can reflect the degree of liver necrosis indicated by aminotransferase levels. Regarding the higher incidence rate of HBV-associated complications in 50 to 60-year-old men, monitoring the antibody can be beneficial in managing this group of CHB patients, which deserves further investigation.

A novel label-free electrochemical immunosensor for the detection of heat shock protein 70 of lung adenocarcinoma cell line following paclitaxel treatment using l-cysteine-functionalized Au@MnO2/MoO3 nanocomposites.

The future trend in achieving precision medicine involves the development of non-invasive cancer biomarker sensors that offer high accuracy, low cost, and time-saving benefits for risk clarification, early detection, disease detection, and therapeutic monitoring. A facile approach for the synthesis of MoO3 nanosheets was developed by thermally oxidizing MoS2 nanosheets in air followed by thermal annealing. Subsequently, Au@MnO2 nanocomposites were prepared using a combined hydrothermal process and in situ chemical synthesis. In this study, we present a novel immunosensor design strategy involving the immobilization of antiHSP70 antibodies on Au@MnO2/MoO3 nanocomposites modified on a screen-printed electrode (SPE) using EDC/NHS chemistry. This study establishes HSP70 as a potential biomarker for monitoring therapeutic response during anticancer therapy. Impedance measurements of HSP70 on the Au@MnO2/MoO3/SPE immunosensor using EIS showed an increase in impedance with an increase in HSP70 concentration. The electrochemical immunosensor demonstrated a good linear response in the range of 0.001 to 1000 ng mL-1 with a detection limit of 0.17 pg mL-1 under optimal conditions. Moreover, the immunosensor was effective in detecting HSP70 at low concentrations in a lung adenocarcinoma cell line following Paclitaxel treatment, indicating its potential for early detection of the HSP70 biomarker in organ-on-a-chip and clinical applications.

363. Autoimmune Sensory Neural Hearing Loss Apparently Triggered by Neurocysticercosis

Abstract Background Meniere’s disease (MD) occurs when an abnormal amount of fluid causes increased pressure in the inner ear or labyrinth. People with Meniere's can experience symptoms including vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Various triggers for MD have been recognized and range from smoking and alcohol consumption to recent viral illness, allergies and anxiety. We present the case of a 37 year old Hispanic male, who presented with dizziness and tinnitus, which progressed to include left sided sensorineural hearing loss and he was diagnosed with Meniere’s Disease, later found to be triggered by Neurocystercercosis. Methods Case report based on chart review. Results The patient's laboratory work up was positive for anti-HSP antibody and he had an abnormal electrocochleography, left greater than right. His vestibulonystagmogram was positive for both central and peripheral findings and bithermal caloric irrigations suggested abnormal peripheral function with a 57% weakness in the left ear. The patient was also referred to rheumatology and neurology. Neurodiagnostic work up included an MRI which revealed a post inflammatory calcification in the right parietal lobe and patient was presumed to have neurocystercercosis. He was treated with steroids, betahistine, and a low salt diet for his MD. Conclusion To our knowledge, this is the first reported case in the literature of Meniere’s disease that may have been triggered by or concurrent with neurocysticercosis. This highlights the importance of a thorough work up to look for neurologic comorbidity for patients presenting with Meniere’s disease. Neurocystercercosis is typically seen developing countries and is caused by the larval form of the parasite Taenia solium infecting the central nervous system. It commonly presents with seizures and such a manifestation associated with Meniere’s disease has not been previously reported. Disclosures All Authors: No reported disclosures.

Serum Anti-heat Shock Protein 27 Antibody Titers in Patients With Dyslipidemia: A Population-based Case-control Study

Background: Heat shock protein 27 (HSP27) is found in several cell types of adults, such as cardiomyocytes, and endothelial cells. It is expressed in response to different cellular stress conditions. HSP27 decreases the levels of reactive oxygen species (ROS) and dyslipidemia is closely associated with increased endothelial production of reactive oxygen species (ROS). Objective: Higher serum HSP27 antigen and anti-HSP27 antibodies have been reported in patients with unstable angina and myocardial infarction Methods: This population-based case-control study was conducted in 2018. We investigated serum anti-HSP27 antibody titers in all participants with dyslipidemia from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study (n=8141) and those who were healthy in terms of dyslipidemia (n=1637) using an in-house enzyme-linked immune sorbent assay (ELISA) in individuals with dyslipidemia. Findings: Anti-HSP27 titers were significantly lower in individuals with dyslipidemia compared to people without dyslipidemia (P=0.036). Conclusion: Our results revealed that the anti-HSP27 antibody titer was lower in the participants with dyslipidemia than in the negative group. However, there may be a confounding effect of drug therapy. In a subgroup of dyslipidemic subjects, we observed lower anti-HSP27 antibody titers in patients treated with some drugs (statins or corticosteroids, non-steroidal anti-inflammatory drugs [NSAIDs], or anti-diabetic and anti-hypertensive) compared to subjects untreated with these drugs.

Effects of vitamin D3-fortified low-fat yogurt and milk on serum cytokine levels and anti hsp-27 antibody titer in adults with abdominal obesity: A randomized clinical trial

The purpose of the current study was to evaluate the effects of nano-encapsulated 25(OH)D fortified (1500 IU Nano-encapsulated 25(OH)D dairy products on anti-heat shock protein 27 antibody (anti-Hsp27) titers, pro-oxidant-antioxidant balance (PAB) and cytokines concentration in adults with abdominal obesity. This study was part of SUVINA project and designed as a randomized trial. Middle aged adults (n = 306) recruited among students and staff of Mashhad University of Medical Sciences [Iran]. Subjects were randomly assorted into four groups: a low-fat yogurt fortified with 1500 IU 25(OH)D (n = 76), and unfortified yogurt (n = 77), a low-fat milk fortified with 1500 IU 25(OH)D (n = 76), and unfortified milk (n = 77) were followed up for 10 weeks. A total of 289 subjects completed the study. Body mass index (BMI) and waist circumference were measured before and after the ten weeks of intervention. The following biochemical markers were determined: serum pro-oxidant-antioxidant balance (PAB), 25(OH) D, anti-Hsp27 titers and cytokines concentration, at baseline and at the end of the study. There was a significant difference between serum 25(OH)D concentration and PAB at baseline and the end of intervention with fortified milk and yogurt. After the intervention period, changes between groups of intervention group of both of the milk and yogurt and control group were statistically significant for serum 25(OH)D concentration (p < 0.001) and PAB (p < 0.05). In the group provide with fortified milk, waist circumference was decreased (−2.01 ± 3.85 cm, p < 0.05) and serum 25(OH)D concentration increased significantly (5.02 ± 4.07 ng/ml, p < 0.001). In the group taking the fortified yogurt, serum 25(OH)D status increased by 6.75 ± 3.42 ng/ml (p < 0.001) and PAB decreased by −21.85 ± 48.07 HK (p < 0.05). Our results did not show any significant differences in mean weight between the groups (p > 0.05). Our results showed that after the intervention with 25(OH)D fortified yogurt or milk in obese subjects, serum PAB concentrations decreased and serum 25(OH)D increased significantly. Therefore, fortification of low-fat yogurt and milk with 25(OH)D may be effective in reducing the pro-oxidant anti-oxidant balance with effect thsat are greater than for unfortified dairy products. • The oxidative stress is seen in obese individuals, such as dysregulation in Pro-oxidant-Antioxidant Balance (PAB). • One of the prescibed dietary interventions for fighting against the obesity-induced oxidative stress is the vitamin D supplementation. • Serum PAB concentration was decreased after intervention with vitamin D fortified yogurt in obese subjects.

Mid-Liver Stage Arrest of Plasmodium falciparum Schizonts in Primary Porcine Hepatocytes.

During co-evolution Plasmodium parasites and vertebrates went through a process of selection resulting in defined and preferred parasite-host combinations. As such, Plasmodium falciparum (Pf) sporozoites can infect human hepatocytes while seemingly incompatible with host cellular machinery of other species. The compatibility between parasite invasion ligands and their respective human hepatocyte receptors plays a key role in Pf host selectivity. However, it is unclear whether the ability of Pf sporozoites to mature in cross-species infection also plays a role in host tropism. Here we used fresh hepatocytes isolated from porcine livers to study permissiveness to Pf sporozoite invasion and development. We monitored intra-hepatic development via immunofluorescence using anti-HSP70, MSP1, EXP1, and EXP2 antibodies. Our data shows that Pf sporozoites can invade non-human hepatocytes and undergo partial maturation with a significant decrease in schizont numbers between day three and day five. A possible explanation is that Pf sporozoites fail to form a parasitophorous vacuolar membrane (PVM) during invasion. Indeed, the observed aberrant EXP1 and EXP2 staining supports the presence of an atypical PVM. Functions of the PVM include the transport of nutrients, export of waste, and offering a protective barrier against intracellular host effectors. Therefore, an atypical PVM likely results in deficiencies that may detrimentally impact parasite development at multiple levels. In summary, despite successful invasion of porcine hepatocytes, Pf development arrests at mid-stage, possibly due to an inability to mobilize critical nutrients across the PVM. These findings underscore the potential of a porcine liver model for understanding the importance of host factors required for Pf mid-liver stage development.

Heat shock protein 70 (HSP70) plays important role in tembusu virus infection

Tembusu virus (TMUV) is an avian-origined flavivirus that is prevalent in ducks and geese. TMUV causes reduced egg production and neurological problems, resulting in profound economic losses to the waterfowl industry. In the viral life cycle, cellular factors are required for viral entry, replication, assembly, release and so on. Heat shock protein 70 (HSP70) is reported to be involved in the replication of multiple viruses. In this study, we explored the roles of HSP70 in the TMUV life cycle. The results showed that TMUV infection induced HSP70 expression starting 12 h post-infection. An HSP70 inhibitor reduced TMUV viral RNA production and the number of virus particles, whereas an HSP70 activator enhanced the amount of viral RNA and virions that released from the cells. Further analysis revealed that HSP70 played important roles in the postentry stages of the TMUV life cycle, including viral replication, assembly and release. We also found that inhibition of HSP70 expression significantly reduced TMUV-induced apoptosis. Additionally, incubation of TMUV particles with an anti-HSP70 antibody significantly reduced viral infectivity, suggesting an association between HSP70 and TMUV particles. These results implicate HSP70 in the life cycle of TMUV, and therefore, targeting HSP70 may be a strategy for developing an anti-TMUV therapy.

Sonosensitized Aggregation-Induced Emission Dots with Capacities of Immunogenic Cell Death Induction and Multivalent Blocking of Programmed Cell Death-Ligand 1 for Amplified Antitumor Immunotherapy

Sonosensitized Aggregation-Induced Emission Dots with Capacities of Immunogenic Cell Death Induction and Multivalent Blocking of Programmed Cell Death-Ligand 1 for Amplified Antitumor Immunotherapy

Are IgG antibodies to heat shock proteins HSP27 and HSP60 useful markers in endometrial cancer and cervical cancer?

Heat shock proteins are overexpressed in many human malignancies. The role of heat shock proteins as a therapeutic target in cancer as well as their association with drug resistance were widely documented. The aim of this study was to evaluate the concentration of IgG class HSP27 and HSP60 antibodies in serum of patients with endometrial and cervical cancer, as well as to analyse the variability of concentrations of the examined antibodies depending on the cancer stage. The study included 59 women with adenocarcinoma of the endometrium and 36 women with cervical cancer, the control group consisted of 54 healthy women. The concentrations of IgG class antibodies against the tested heat shock proteins were determined by an immunoenzymatic assay (ELISA) using commercial assays. In both endometrial and cervical cancer, the serum concentration of IgG anti-HSP27 antibody was significantly higher than in the healthy control group. The concentration of IgG anti-HSP60 antibody in endometrial cancer, cervical cancer and healthy control was similar. The median IgG anti-HSP27 antibody serum concentration of endometrial cancer patients was not correlated with FIGO-stage. In cervical cancer inverse correlation between concentration of this antibody and FIGO stage was observed. The median IgG anti-HSP60 antibody concentration in serum of endometrial cancer patients was lower in FIGO stage I and II compared to FIGO stage IV and in FIGO stage IA compared to FIGO stage IB. Concentrations of examined antibodies correlated positively with each other, both in the group of women with cancer and in the group of healthy women. The strongest correlations were found in the group of patients with endometrial cancer. Concentration of anti-HSP27 antibody could help in detection of cervical and endometrial cancer. We need to look for the cut-off point in large cohort studies. Anti-HSP27 and anti-HSP60 antibodies should be further evaluated for their potential usage as biomarkers in cervical and endometrial cancer as they shown some correlation with stage of disease.

Physical activity level (PAL) and risk factors of cardiovascular disease in the MASHAD study cohort

Background and aimThe relationship between physical activity levels (PAL) and the presence of cardiovascular disease (CVD) risk factors such as anthropometric and biochemical indices and heat shock proteins 27 antibody (anti-HSP-27) concentration, and serum inflammatory markers, was investigated in the MASHAD cohort study. MethodsThe overall study population consisted of 9,684 subjects (3,858 men, 5,826 women) with a mean age of 47.73 ± 8.08 to 48.87 ± 9.26 years respectively. They were divided into four categories based on their PAL. Biochemical parameters were determined for all participants. Also, serum anti-HSP-27 levels were measured using an in-house enzyme-linked immune sorbent assay method. Multiple regression analysis was used to explore the association between the anti-HSP antibody titers and physical activity after adjusting for confounding factors. The level of statistical significance was set at p < 0.05. ResultsSeveral CVD risk factors were associated with the level of PAL including: body mass index, waist hip ratio, systolic and diastolic blood pressure, serum HDL-C and TG (p < 0.001) and also fasting blood glucose (0.004). Also, serum anti-HSP-27 titers were significantly higher in inactive subjects (P > 0.05). ConclusionWe found that PAL was significantly associated with several established CVD risk factors. Also, the level of anti-HSP-27 was lower in individuals with moderate and high PAL.

Electrochemical detection of heat shock protein 70 over cost-effective plastic chip electrode platform

BackgroundEarly diagnosis of cancer can help not only in saving precious lives but also in reduction of the disease management expenses due to the effective and shorter anti-cancer treatment. Heat shock protein 70 (HSP70) is a cancer biomarker whose level is increased in a plethora of cancerous tumors. Therefore, this work is focused on the development of cost-effective label-free biosensing over a novel plastic chip electrode (PCE) platform for highly sensitive and selective detection of the HSP70 biomarker. MethodsThe gold-coated surface of PCE was modified with 4-aminothiophenol and glutaraldehyde linking chemistry, and further immobilized with a bioreceptor anti-HSP70. Further, sensing experiments were performed using differential pulse voltammetry. FindingsThe results confirmed the successful surface modifications and immobilization of the anti-HSP70 antibody on the PCE platform. PCE electrochemical biosensor displayed the highly sensitive detection of the HSP70 in the wide linear range of 0.01-1000 ng/mL and a low limit of detection (LOD) of 3.5 pg/mL at 3σ. Also, HSP70 detection from the serum samples with excellent sensitivity, accuracy and specificity was demonstrated. Overall, the novel PCE biosensor has demonstrated great promise for highly sensitive and selective detection of the HSP70 cancer biomarker.