Plasma Hsp70 Research Articles

Chronic whole-body heat treatment in obese insulin-resistant C57BL/6J mice

Aim This study examined the effects of hyperthermic therapy (HT) on mice fed normal chow or a high-fat diet (HFD) for 18 or 22 weeks, undergoing four or eight weekly HT sessions. Methods Mice were housed within their thermoneutral zone (TNZ) to simulate a physiological response. HFD-induced obesity-related changes, including weight gain, visceral fat accumulation, muscle loss (indicative of obesity sarcopenia), glucose intolerance, and hepatic triglyceride buildup. Main Results HT upregulated HSP70 expression in muscles, mitigated weight gain, normalised QUICK index, and reduced plasma HSP70 concentrations. It also lowered the H-index of HSP70 balance, indicating improved immunoinflammatory status, and decreased activated caspase-1 and proliferative senescence in adipose tissue, both linked to insulin resistance. Conclusion The findings suggest that even animals on a “control” diet but with insufficient physical activity and within their TNZ may experience impaired glycaemic homeostasis.

Unveiling the role of exercise in modulating plasma heat shock protein 27 levels: insights for exercise immunology and cardiovascular health.

Cardiovascular disease is one of the leading causes of mortality worldwide, primarily driven by atherosclerosis, a chronic inflammatory condition contributing significantly to fatalities. Various biological determinants affecting cardiovascular health across different age and sex groups have been identified. In this context, recent attention has focused on the potential therapeutic and preventive role of increasing circulating levels of heat shock protein 27 (plasma HSP27) in combating atherosclerosis. Plasma HSP27 is recognized for its protective function in inflammatory atherogenesis, offering promising avenues for intervention and management strategies against this prevalent cardiovascular ailment. Exercise has emerged as a pivotal strategy in preventing and managing cardiovascular disease, with literature indicating an increase in plasma HSP27 levels post-exercise. However, there is limited understanding of the impact of exercise on the release of HSP27 into circulation. Clarifying these aspects is crucial for understanding the role of exercise in modulating plasma HSP27 levels and its potential implications for cardiovascular health across diverse populations. Therefore, this review aims to establish a more comprehensive understanding of the relationship between plasma HSP27 and exercise.

Abstract 7521: Tumor NLRP3 inflammasome activity mediates resistance to Anti-PD-1 immunotherapy in advanced gastroesophageal cancer

Abstract The addition of anti-PD-1 immunotherapy to the therapeutic armamentarium of advanced gastroesophageal (GE) cancer patients has resulted in modest improvements in clinical outcomes for a subset of patients. More robust predictive biomarkers to guide patient management and to select optimal combination immunotherapy strategies for the individual patient are needed. Our previous studies indicate that the tumor-intrinsic NLRP3 inflammasome-HSP70 signaling axis promotes the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) and drives resistance to anti-PD-1 immunotherapy. The KEYLargo phase II clinical trial evaluated the efficacy of pembrolizumab (pembro) in combination with capecitabine/oxaliplatin (CAPOX) in HER2-negative advanced GE cancer patients. An 8-day lead-in period of pembro monotherapy in 36 advanced GE cancer patients allowed for the acquisition of blood and tumor tissue specimens to determine which immune-mediated alterations within the tumor microenvironment correlated with resistance to anti-PD-1 immunotherapy. Baseline and on-treatment specimens were collected for HSP70 ELISA, immunofluorescence microscopy, spatial transcriptomics, NLRP3 FISH, IHC, and NLRP3-ASC proximity ligation assays (PLA) to measure NLRP3 pathway activity levels. All data was correlated with best objective response, progression-free survival (PFS), and overall survival (OS). Tumor-infiltrating CD8+ T cells and PMN-MDSCs were increased in responders and non-responders, respectively. While PD-L1 CPS failed to associate with response, elevated baseline NLRP3 PLA activity correlated with increased tumor-infiltrating PMN-MDSCs (P = 0.001) and resistance to pembro/CAPOX therapy (P = 0.01). Only non-responding tumors exhibited an increase in NLRP3 PLA activity and NLRP3 amplification. Transcriptional studies revealed tumors with enhanced NLRP3 activity to exhibit decreased expression of the NLRC5 transactivator, MHC class I antigen presentation genes, and an increase in the NK cell negative regulator, HLA-G. Baseline plasma HSP70 levels correlated with tumor NLRP3 activity (P = 0.043) and with resistance to pembro/CAPOX therapy (P = 0.001). Elevated baseline NLRP3 PLA activity and amplification were associated with diminished PFS (P = 0.008) and OS (P = 0.009). In additional studies, pharmacologic inhibition of the NLRP3 inflammasome suppressed PMN-MDSC recruitment, upregulated MHC class I, and reversed anti-PD-1 resistance in an orthotopic model of GE cancer. Together, these findings implicate tumor-intrinsic NLRP3-HSP70 signaling as an important mediator of anti-PD-1 resistance in advanced GE cancer. The NLRP3-HSP70 pathway is a promising source of therapeutic targets and biomarkers capable of improving treatment outcomes for this patient population. Additional clinical studies are warranted. Citation Format: Nagendra Yarla, Kaylee Howell, Y-Van Nguyen, Donna Niedwiecki, Hope Uronis, John Strickler, Nicholas C. DeVito, Bala Theivanthiran, Brent A. Hanks. Tumor NLRP3 inflammasome activity mediates resistance to Anti-PD-1 immunotherapy in advanced gastroesophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7521.

Variations of Physiological Parameters and HSP70 and HSP90 Polymorphisms in Water Buffaloes in Taiwan During Cool and Warm Season

Background: This study examined the physiological parameters of water buffaloes in Taiwan in the cool (February) and warm (August) seasons of 2020 and 2021.
 Methods: Data was collected for a study in February, August 2020, and 2021. The ambitious temperature, humidity, water buffaloes’ rectal temperature (RT), and respiratory rate (RR) were recorded. The plasma expression levels of heat-shock protein (HSP)70 and HSP90 were examined using an ELISA kit. Furthermore, the HSP70 and HSP90 fragment genetic sequence variations were analyzed using the PCR method and MEGA6 software.
 Results: The results revealed that in the warm season, the rectal temperature (RT), respiratory rate (RR), and heat tolerance coefficient (HTC) were significantly higher compared to the cool season (all P < 0.05). Additionally, the temperature-humidity index (THI) had moderate to high correlations with RT (0.518), RR (0.744), and HTC (0.757). Plasma HSP70 expression levels were higher in the warm season than in the cool season (P < 0.05). The genetic sequences of HSP70 and HSP90 fragments were compared, and five single-nucleotide variation (SNV) sites were identified. However, each genotype showed no significant physiological difference between the cool and warm seasons.
 Conclusion: Temperature and humidity changes in Taiwan had a significant correlation with the physical condition of water buffaloes. This information can be valuable in improving the living conditions of these animals, leading to better animal welfare. Additionally, the HSP70 and HSP90 gene variations in water buffaloes in Taiwan could be used as a reference for future research on breeding and identifying molecular markers.

Effect of organic mineral supplementation in reducing oxidative stress in Holstein calves during short-term heat stress and recovery conditions

BackgroundThis study investigated the effects of inorganic and organic minerals on physiological responses, oxidative stress reduction, and rumen microbiota in Holstein bull calves (123.81 ± 9.76 kg; 5 months old) during short-term heat stress (HS) and recovery periods. Eight Holstein calves were randomly assigned to four treatment groups: no mineral supplementation (Con), inorganic minerals (IM), organic minerals (OM), and high-concentration organic minerals (HOM) and two thermal environments (HS and recovery) using 4 × 2 factorial arrangement in a crossover design of four periods of 35 d. Calves were maintained in a temperature-controlled barn. The experimental period consisted of 14 d of HS, 14 d of recovery condititon, and a 7-d washing period.ResultsBody temperature and respiration rate were higher in HS than in the recovery conditions (P < 0.05). Selenium concentration in serum was high in the HOM-supplemented calves in both HS (90.38 μg/dL) and recovery periods (102.00 μg/dL) (P < 0.05). During the HS period, the serum cortisol was 20.26 ng/mL in the HOM group, which was 5.60 ng/mL lower than in the control group (P < 0.05). The total antioxidant status was the highest in the OM group (2.71 mmol Trolox equivalent/L), followed by the HOM group during HS, whereas it was highest in the HOM group (2.58 mmol Trolox equivalent/L) during the recovery period (P < 0.05). Plasma malondialdehyde and HSP70 levels were decreased by HOM supplementation during the HS and recovery periods, whereas SOD and GPX levels were not significantly affected (P > 0.05). The principal coordinate analysis represented that the overall rumen microbiota was not influenced by mineral supplementation; however, temperature-induced microbial structure shifts were indicated (PERMANOVA: P < 0.05). At the phylum level, Firmicutes and Actinobacteria decreased, whereas Fibrobacteres, Spirochaetes, and Tenericutes increased (P < 0.05), under HS conditions. The genus Treponema increased under HS conditions, while Christensenella was higher in recovery conditions (P < 0.05).ConclusionHOM supplementation during HS reduced cortisol concentrations and increased total antioxidant status in Holstein bull calves, suggesting that high organic mineral supplementation may alleviate the adverse effects of HS.

Tumor-intrinsic NLRP3-HSP70-TLR4 axis drives premetastatic niche development and hyperprogression during anti-PD-1 immunotherapy.

The tumor-intrinsic NOD-, LRR- and pyrin domain-containing protein-3 (NLRP3) inflammasome-heat shock protein 70 (HSP70) signaling axis is triggered by CD8+ T cell cytotoxicity and contributes to the development of adaptive resistance to anti-programmed cell death protein 1 (PD-1) immunotherapy by recruiting granulocytic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into the tumor microenvironment. Here, we demonstrate that the tumor NLRP3-HSP70 axis also drives the accumulation of PMN-MDSCs into distant lung tissues in a manner that depends on lung epithelial cell Toll-like receptor 4 (TLR4) signaling, establishing a premetastatic niche that supports disease hyperprogression in response to anti-PD-1 immunotherapy. Lung epithelial HSP70-TLR4 signaling induces the downstream Wnt5a-dependent release of granulocyte colony-stimulating factor (G-CSF) and C-X-C motif chemokine ligand 5 (CXCL5), thus promoting myeloid granulopoiesis and recruitment of PMN-MDSCs into pulmonary tissues. Treatment with anti-PD-1 immunotherapy enhanced the activation of this pathway through immunologic pressure and drove disease progression in the setting of Nlrp3 amplification. Genetic and pharmacologic inhibition of NLRP3 and HSP70 blocked PMN-MDSC accumulation in the lung in response to anti-PD-1 therapy and suppressed metastatic progression in preclinical models of melanoma and breast cancer. Elevated baseline concentrations of plasma HSP70 and evidence of NLRP3 signaling activity in tumor tissue specimens correlated with the development of disease hyperprogression and inferior survival in patients with stage IV melanoma undergoing anti-PD-1 immunotherapy. Together, this work describes a pathogenic mechanism underlying the phenomenon of disease hyperprogression in melanoma and offers candidate targets and markers capable of improving the management of patients with melanoma.

Effectiveness of Short-Term Heat Acclimation on Intermittent Sprint Performance in the Heat with Moderately Trained Males

Purpose: Effectiveness of short-term heat acclimation (STHA), over 5-days (permissive dehydration), on intermittent heat stress test (HST) with males. Methods: Ten, moderately-trained, males (mean [SD]; age 25.6 [8.9] y; stature 180.7 [5.6] cm; body mass 83.2 [10.8] kg; and 45.3 [6.5] mL.kg-1.min-1) participated. The HST was 9 x 5min (45-min) of intermittent exercise based on professional soccer players. One week apart, HST1 vs HST (11.0°C; 50%RH), as a reliability trial and HST3 in 31.0°C; 50%RH were completed. Then 90 min dehydration, STHA (no fluid intake), for 5 consecutive days (39.5oC; 60%RH), using controlled-hyperthermia (~rectal temperature [Tre] 38.5oC). The HST4 within one week after STHA. Blood plasma constituents: percent plasma volume (%PV), aldosterone, total protein, albumin, electrolytes, cortisol and HSP70. Data analysis reported as mean differences with 95% confidence intervals (95%CI) and Cohen’s d effect size. Results: Post STHA, there was a decrease of -0.20 Tre at 45-min in the HST (95%CI -0.40 to -0.05°C; P=0.03; d =-0.56); mean skin temperature (-0.80; -1.30 to -0.30°C; P=0.007; d =-1.46) and mean body temperature (-0.30; -0.50 to -0.10°C, P=0.01; d =-0.75). Cardiac frequency reduced (-3: -5 to -1 b.min-1; P=0.01; d =-0.20) and %PV increased (7.3: 0.9 to 13.7%; P=0.03; d=0.59). Mean Peak Power (MPO) increased (Pd =0.63). Conclusions: Short-term heat acclimation (5-days) with dehydration, using controlled-hyperthermia technique, is effective for physiological adaptations during intermittent exercise in the heat, with moderately trained males.

319 The tumor-intrinsic NLRP3 inflammasome establishes a pulmonary metastatic niche via type II epithelial HSP70/TLR4 signaling and facilitates disease hyperprogression in response to immunotherapy

BackgroundOur understanding of those underlying mechanisms that contribute to metastatic progression in melanoma remains limited. While uncommon, melanoma hyperprogression in response to immunotherapy is likely to be an extreme form of acquired resistance. Therefore, studies that define the underlying mechanisms of these processes are expected to provide insight into the discovery of novel therapeutic targets and predictive biomarkers. We previously demonstrated that tumor-intrinsic NLRP3 drives adaptive resistance to anti-PD-1 immunotherapy (anti-PD-1) by inducing the recruitment of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) via the upregulation of CXCL5. Gain-of-function polymorphisms in the TLR4 gene have been associated with pulmonary metastases in melanoma patients. We have shown HSP70 to promote PMN-MDSC chemotaxis via the stimulation of TLR4 signaling. As a result, we hypothesized that the tumor NLRP3 inflammasome may also contribute to distant metastatic progression and disease hyperprogression during immunotherapy by establishing a long-distance signaling axis mediated by HSP70-TLR4 signaling in the lung.MethodsWe pharmacologically and genetically inhibited the NLRP3 inflammasome and HSP70 in a transgenic BRAFV600E mouse model to examine their role in distant metastatic progression before and during anti-PD-1. An inducible type II pulmonary epithelial cell-specific TLR4 knock-out mouse model was engineered to examine the role of distant HSP70-TLR4 signaling in the recruitment of PMN-MDSCs and subsequent metastatic progression to the lung. Plasma HSP70 levels were monitored in melanoma patients undergoing anti-PD-1ResultsAnti-PD-1 significantly increases CXCL2/CXCL5 expression and PMN-MDSC accumulation in the lungs of the transgenic BRAFV600E model. This effect is reversed by 1) tumor-targeted ablation and pharmacologic inhibition of NLRP3 but not systemic host knock-out of NLRP3, 2) Pharmacologic Wnt5a ligand inhibition, 3) tumor-specific ablation and inhibition of HSP70. Inducible knock-out of TLR4 in type II epithelial cells suppressed Wnt5a and CXCL5 expression and inhibited the recruitment of PMN-MDSCs to the lung in response to anti-PD-1. Tumor-specific inhibition of NLRP3/HSP70 and lung-specific ablation of TLR4 suppressed metastatic progression following anti-PD-1 in the BRAFV600E melanoma model. Combination anti-PD-1 and NLRP3 inhibition suppressed primary melanoma progression and distant melanoma metastases versus anti-PD-1 monotherapy. Elevated plasma levels of HSP70 were associated with disease hyperprogression in metastatic melanoma patients undergoing anti-PD-1Abstract 319 Figure 1Tumor-intrinsic NLRP3 inflammasome and metastasisConclusionsTogether, these results describe a novel cross-talk mechanism between the primary tumor and the lung that mediates distant metastatic progression that is accentuated following anti-PD-1 (figure 1). Future clinical studies are needed to evaluate the pharmacologic inhibition of this tumor-lung NLRP3/HSP70/TLR4/Wnt5a/CXCL5 axis on melanoma metastasis and disease hyperprogression during checkpoint inhibitor immunotherapy

Reaction Kinetics Modeling of eHsp70 Induced by Norepinephrine in Response to Exercise Stress.

Exercise elicits a systemic adaptation reaction, involving both neuroendocrine and cellular/paracrine stress responses, exemplified by the sympathoadrenergic activity and the release of cellular Hsp70 into the circulation. Regular sports training is known to result in increased fitness. In this study, we characterized the plasma norepinephrine and Hsp70 levels and modeled their relationship in response to exercise stress by bicycle ergometer in 12 trained judoka athletes and in 10 healthy controls. Resting norepinephrine was similar in both groups, whereas Hsp70 was significantly higher in controls compared to athletes. Intense exercise load induced both norepinephrine and Hsp70 elevation. However, both norepinephrine and Hsp70 were significantly lower in athletes compared to the control group. A reaction kinetic model was developed that provided a quantitative description of norepinephrine-facilitated extracellular Hsp70 release, congruent with the experimental data. Our study indicates that exercise-induced norepinephrine and extracellular Hsp70 may be coordinated responses to physiological stress, which are robustly affected by regular sports activity.

The inflammatory markers sST2, HSP27 and hsCRP as a prognostic biomarker panel in chronic heart failure patients

BackgroundThe inflammatory markers sST2, HSP27 and hsCRP have already been identified as prognostic markers in chronic heart failure (HF). Though individual biomarkers have proven their value in mortality risk prediction, the role of a multimarker strategy needs further evaluation. Materials and MethodsThis is an exploratory reanalysis in chronic HF patients. Plasma HSP27, sST2 and hsCRP in outpatients with chronic HF were analysed. Patients were followed for a minimum of twelve months for the endpoint cardiovascular mortality and unplanned HF associated hospitalisation (=event). 15 year overall mortality was assessed retrospectively. The prognostic impact was assessed using a Cox proportional hazard model. Results113 chronic HF patients were included. Median follow up time was 614 days and 37 patients (32.7%) experienced an event. A Kaplan-Meier analysis revealed that patients with increased sST2, HSP27 and hsCRP levels have significantly worse prognosis (p < 0.001). The use of a three-biomarker combination was superior in an independent risk prediction of an event (one high vs. two high: HR = 4.5, 95% CI: 1.3–15.5, p = 0.018; and one high vs. all high: HR = 9.8, 95% CI: 2.8–34.3, p < 0.001) as shown in a multivariable cox proportional hazard model. However, the biomarker panel did not predict 15 year overall mortality, in contrast to elevated HSP27 levels (p = 0.012). ConclusionsThe combination of all three markers is an independent predictor of cardiovascular death and unplanned HF associated hospitalisation but not overall mortality. Our findings suggest that adding those markers in combination to well established risk assessment parameters may improve risk stratification.

Impact of pre-slaughter transport conditions on stress response, carcass traits, and meat quality in growing rabbits

In growing rabbits (n = 320; 84 d of age), an increase in the journey duration to the slaughterhouse from 1 h to 3 h under mild climatic conditions (10–13 °C; 75–90% relative humidity) affected several stress indicators in the plasma and muscle collected at slaughter (cortisol; corticosterone; lactate dehydrogenase, LDH; lactate; heat shock protein 70 kDa, HSP70; osmolality, and Na) (0.001 < P < .05), reduced muscle L*, b* (P < .01), and meat shear force (P < .05), and increased the dressing out percentage and muscle pH (P < .01). An increase in the lairage duration before slaughtering from 30 min to 3 h affected muscle cortisol and plasma creatinine kinase, LDH, lactate, and HSP70 (0.001 < P < .05), increased dressing out percentage and muscle pH (P < .05), but decreased meat shear force (P < .001). The interaction between journey and lairage duration was significant for several stress indicators and meat quality.

PI3K/Akt signaling pathway and Hsp70 activate in hippocampus of rats with chronic manganese sulfate exposure

Manganese (Mn) has come to the forefront of environmental concerns due to its neurotoxicity. However, the toxic effect of Mn is not fully understood. The purpose of this study is to investigate the impacts of chronic manganese sulfate (MnSO4) exposure in regulating the phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway in rats. In this study, rats were treated with 0, 5.0, 10.0, and 20.0 mg/kg MnSO4•H2O five days a week for 24 weeks via intraperitoneal injection. At the end of the exposure period, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), and heat shock protein (Hsp70) in rats’ plasma were quantified; the mRNA expression levels of caspase-3, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), serine-threonine protein kinase (Akt-1), and forkhead box O3a (FoxO3a) were measured through real-time quantitative PCR (RT-PCR); and the levels of protein Hsp70 and Akt were assessed by western blot. With an increasing dose of MnSO4, the organ coefficients of all tested organs were significantly increased, except the testis. Compared with the control group, the activities of plasma SOD, GSH-Px, and CAT in MnSO4-exposed groups were significantly decreased, while the concentrations of plasma MDA and Hsp70 were significantly increased. Moreover, the hippocampal mRNA levels of Bcl-2, caspase-3, Akt-1, and FoxO3a in MnSO4-exposed groups were downregulated, but the level of Bax was upregulated. Meanwhile, the level of phosphorylation of Akt (p-Akt) and Hsp70 proteins tends to be upregulated by increasing MnSO4 exposure (P < 0.05). The plasma Hsp70 level was negatively associated with SOD, CAT, and GSH-Px activities (P < 0.05), and positively associated with blood MDA concentration and hippocampal Hsp70 levels (P < 0.05). Chronic MnSO4 exposure can result in apoptosis of central nerve cells, activate the PI3K/Akt signaling pathway in rats’ hippocampus, and upregulate Hsp70 transcription and translation.

Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics.

Type 2 diabetes mellitus (T2DM) features insulin resistance, hyperglycemia, dyslipidemia, overproduction of inflammatory cytokines, and systemic oxidative stress. Here, heat shock proteins Hsp70 and Hsp 90, adiponectin, and heme oxygenase-1 (HO-1, Hsp32) are profiled in peripheral blood mononuclear cells (PBMC) and serum from 25 T2DM patients and 25 healthy control subjects. Cells cultured with phorbol 12-myristate 13-acetate/ionomycin were evaluated by three-color flow cytometry for immunophenotypic biomarkers. Plasma HO-1, Hsp, and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA). Relative to healthy controls, T2DM patients exhibited significantly elevated plasma Hsp70, and representation of T helper immunophenotypes activated to express inflammatory cytokines, including CD4+ IFN-γ+, CD4+ TNF-α+, CD4+ IL-6+, CD4+ IL-1β+ T cells, significantly lower representation of CD4+ IL-10+ T cells, plasma adiponectin and cell-associated HO-1 expression-with no significant differences in plasma Hsp90 between T2DM and healthy controls. Plasma HO-1 and adiponectin in T2DM patients inversely correlated with TNF-α and showed inverse correlation between serum LDL and plasma HO-1. Moreover, TNF-α and Hsp90 in T2DM patients correlated positively with fasting blood glucose (FBG). These results demonstrate correlation between potentially pathogenic T cells, HO-1, and adiponectin, additionally revealing a T helper (Th)1-related character of T2DM immunopathogenesis, suggesting potential for novel T cell-related management strategies for T2DM and related co-morbidities.

Adaptation strategies of yak to seasonally driven environmental temperatures in its natural habitat.

The gradual increase of ambient temperature (TA) at high altitude can cause heat stress as an effect of climate change and may shift the traditional habitat of yak to further higher altitude. Therefore, an attempt has been made in this study to evaluate the thermo-adaptability of yaks to different seasons at high altitude. The adaptive capabilities of yaks were assessed based on different heat tolerance tests in relation to changes in rectal temperature (RT; °F), respiration rate (RR; breaths/min), pulse rate (PR; beats/min), and plasma heat shock protein (HSP) profile. The experiment was conducted in 24 yaks, divided into three groups based on age as calf (n = 8), adult (n = 8), and lactating cow (n = 8). Thermal adaptability was determined by temperature humidity index (THI), dairy search index (DSI), and Benezra's thermal comfort index (BTCI) along with HSP70 profile. The THI was higher (P < 0.01) in summer than winter which increased from lowest (40.87) to highest (61.03) in summer by 20 points, where yaks were under heat load beyond THI 52. The RT (100.09 ± 0.18°F), RR (21.76 ± 0.18), and PR (59.78 ± 0.32) increased by 23-35%, and this was correlated to the higher values of DSI exceeding 1 in calves (1.35 ± 0.03), lactating cows (1.29 ± 0.04), and adults (1.23 ± 0.32) during summer in comparison to winter (0.98 ± 0.02). The BTCI also showed values greater (P < 0.01) than 2 in calves (3.47 ± 0.27), lactating cows (3.23 ± 0.28), and adults (2.98 ± 0.29) which reflected 49-75% increase in rectal temperature and respiration rate during summer. Further, heat stress was substantiated by threefold higher (P < 0.01) level of plasma HSP70 in calves (189.61 ± 3.90pg/ml) followed by lactating cows (168.62 ± 3.03pg/ml) and adults (155.33 ± 2.30pg/ml) against the winter average of 87.92 ± 3.19pg/ml. Present results revealed that yaks were experiencing heat stress in summer at an altitude of 3000m above sea level and calves were more prone to heat stress followed by lactating cows and adults.

Utilizing original XPC™ in feed to reduce stress susceptibility of broilers

Reduction of stress is an important factor in improving poultry welfare, especially during periods of heat stress. A study was conducted to evaluate the effects of feeding the functional metabolites of Diamond V Original XPCTM to broilers reared under ambient or heat stress temperatures. Dietary treatments included: control feed (CON) and Original XPC fed continuously at 1.25kg/MT (XPC). Half the birds in each dietary treatment were subjected to either no heat stress (24°C constant) or heat stress (35°C:24°C for 18:6h daily) from 28 to 42 d. At the end of the heat stress period, blood was collected from 40 birds/treatment. Blood was analyzed for plasma corticosterone (CORT), plasma HSP70 (HSP70), and heterophil/lymphocyte ratios (H/L). At 42 d, bilateral metatarsal traits were also measured in 40 birds/treatment to assess physical asymmetry. Birds fed XPC had significantly lower CORT levels than CON (P <0.001; 5,129±617vs. 8,433±730, respectively). Physical asymmetry scores were also significantly higher in CON compared to XPC fed broilers (P <0.001; 1.50±0.13vs. 0.54±0.05, respectively). H/L ratios were significantly greater in CON than for XPC birds (P = 0.01; 0.81±0.05mm vs. 0.62±0.05mm, respectively). No differences were observed between CON and XPC fed broilers in HSP70. However, heat stress did increase (P <0.0001) HSP70 compared to no heat stress birds (5.65±0.12vs. 4.78±0.11 pg/mL, for heat stress and no heat stress, respectively). Feeding XPC to broiler chickens improved animal welfare via reduced stress indicators while under heat stress or no heat stress conditions. These results indicate that feeding XPC may improve poultry welfare by reducing heat stress susceptibility.

Diurnal variation and oscillatory patterns in physiological responses and HSP70 profile in heat stressed yaks at high altitude

ABSTRACTThe present study was carried out at altitude of 3000 m above sea level (asl) to evaluate the impact of heat stress on yak adaptability. Sixteen healthy yaks of different age were randomly divided into two groups, calf (GI; n = 8) and adult (GII; n = 8). Experimental yaks were exposed to heat stress in the open paddock. THI ranged between 61.60 and 64.17 which were beyond the comfortable limit for yak. Post-exposure, rectal temperature increased (p < 0.01) by 2.97 °F and 2.42 °F in calf and adult yaks as compared to pre-exposure (100.08 ± 0.04 °F, 100.06 ± 0.05 °F). Respiration rate increased (p < 0.01) by 2.96 and 2.40 fold in calf and adult yaks with increased pulse rate on post-exposure to heat stress. The oscillatory patterns of physiological responses indicated that the level of heat stress increment was higher (p < 0.05) in calves than adult yaks. Plasma HSP70 increased (p < 0.01) by 7 fold in calf and 5 fold in adult yaks in comparison to pre-exposure level of 83.67 ± 1.11pg/ml and 80.65 ± 1.35 pg/ml. Thus, the yaks were experiencing heat stress at high altitude of 3000 m asl during the warmer months of the year and calves were more prone to heat stress as compared to adults.

Effects of the season on physiological and endocrine traits and on HSP70 in Saanen goats under Mediterranean climate conditions

This study was conducted to determine the impact of heat stress on some physiological and endocrine traits in Saanen goats raised under Mediterranean climate conditions. The effects of thermal stress on heart rate (HR), respiration rate (RR) and rectal temperature (RT) on plasma total trii-odothyronine (T3), thyroxine (T4), Cortisol (C), and HSP70 concentrations were evaluated on twenty two Saanen goats of different ages in the second week of April 2013, July 2013, October 2013 and January 2014. Climatic data such as temperature (°C) and relative humidity (%) were recorded from Spring 2013 to Winter 2014. Live body and BCS values were also recorded during this period. The physiological parameters above were measured twice on each experiment day (morning and afternoon) in all seasons. Blood samples were collected in each afternoon of the experiment day to analyze T3, T4 C, and HSP70. All data were analyzed. According to the values of rectal temperature (RT), it was estimated that the goats were under extreme heat stress only in the summer season. The heart rate (HR) values in the winter season for morning and noon periods were found statistically significant (p &lt; 0.05). The average respiratory rate (RR) in the spring season was found significantly lower. On the other hand, the RR for the noon period in the summer was higher than in the fall and winter seasons (p &lt; 0.05). There was a significant difference (p &lt; 0.05) between summer and fall seasons for C values. The highest value (96.62 ng/ml) was obtained in spring, whereas the lowest (60.58 ng/ml) in the fall. T3 levels in the fall and winter were found to be statistically significant (p &lt; 0.05). They were the highest in the winter and spring, and the lowest in fall. T4 and T4/T3 levels in the winter were found to be statistically higher than in other seasons (p &lt; 0.05). The lowest value for T4 was found in the fall and for T4/T3 in summer. Mean HSP70 value in spring was found to be statistically low (p &lt; 0.05). The changes in THI values in different seasons, particularly between mornings and afternoons, indicated that thermal stress was evident, and that the animals became resistant to it eventually. The fluctuations of the C, T3, T4 and HSP70 values were indicators of the animals’ reaction to thermal stress. The THI values in spring, which were between 16 and 18 THI, may be considered within the ideal comfort zone for goats. It was observed that Saanen goats were able to adapt to seasonal weather changes in the environmental conditions of the region....

Elevated circulating heat shock protein 70 and its antibody concentrations in chronic spontaneous urticaria.

Heat shock proteins (Hsp) play a complex role in cytoprotection, inflammation, and function of the immune system. They may be involved in pathogenesis of various diseases. Our aim was to determine circulating Hsp70 and anti-Hsp70 antibodies concentrations in patients with chronic spontaneous urticaria (CSU). Concentrations of Hsp70 in plasma and anti-Hsp70 antibodies in serum as well as serum C-reactive protein (CRP) were measured in CSU patients and in the controls. Plasma Hsp70 concentrations were significantly higher in CSU (all) and mild CSU patients as compared with the controls. Moderate–severe CSU patients tended to show higher Hsp70 concentration as compared with the controls, but not with mild activity of the disease. There were no significant differences in Hsp70 concentration between moderate–severe and mild CSU patients. Serum anti-Hsp70 antibodies concentrations were significantly higher in CSU (all) and mild CSU in comparison to the controls. Association was observed between anti-Hsp70 antibodies and increased CRP concentration; however, no correlation between anti-Hsp70 and Hsp70 concentrations was seen in the patients. It seems that up-regulation of Hsp70 in CSU may induce marked increase in anti-Hsp70 antibodies production, which are accompanied by parallel changes in CRP concentration. We suggest that Hsp may be released in CSU in response to stressful stimuli, such as inflammation.

Circulating levels of Hsp27 in microvascular complications of diabetes: Prospects as a biomarker of diabetic nephropathy

AimHeat shock protein 27 (Hsp27) is a small heat shock protein known to protect the cells from apoptosis under stress. In the present study, we determined the plasma Hsp27 levels in type 2 diabetes subjects without and with microvascular complications- diabetic retinopathy (DRe), diabetic nephropathy (DNe), and diabetic neuropathy (DNu) to understand if it could serve as a marker for these complications. MethodsThis is a hospital-based case-control study with 754 subjects including 247 controls, 195 subjects with diabetes, 123 with DRe, 80 with DNe and 109 with DNu. Plasma Hsp27 levels were measured by ELISA. ResultsThe mean plasma Hsp27 was higher in the DNe group (631.5±355.2) compared to the control (496.55±308.54), diabetes (523.41±371.01), DRe (494.60±391.48) and DNu (455.21±319.74) groups with a p-value of 0.018. Receiver operating characteristic (ROC) curve analysis of Hsp27 in DNe group showed an area under the curve (AUC) of 0.617. Spearman correlation analysis shows a positive correlation of plasma Hsp27 with serum creatinine (p=0.053, r-value 0.083). Gender, age and BMI did not affect the plasma Hsp27 levels. ConclusionThe plasma Hsp27 levels in the DNe group are higher compared to the control and other complications, thereby it could be explored to be used as a potential biomarker of DNe.

Heat shock protein 27 acts as a predictor of prognosis in chronic heart failure patients.

Heat shock proteins (HSPs) represent intracellular mechanisms of stress response. Clinical implications of their (systemic) expression in patients with chronic heart failure (HF) remain inconclusive. In outpatients with chronic stable HF plasma HSP27 levels were measured using ELISA. Patients were followed for a minimum of one year, and a multivariate Cox proportional hazard model was built for cardiovascular death or HF-associated hospitalisations. A total of 134 patients with chronic HF (mean age 71±10years, 34% female, mean LVEF 36±12%) were included. During a mean follow-up of 527±260days, 44 patients (33%) experienced an event. Mean time to event was 350±236days. In a Kaplan-Meier survival analysis HSP27 levels above the median (3820pg/ml) indicate a higher risk for an event (p=0.03). Increased HSP27 levels remained an independent predictor of events (HR, 2.33 CI 95% 1.12-4.87, p=0.024) even after adjustment for age, gender, NT-proBNP, LVEF, aetiology, smoking status, kidney function and NYHA class. HSP27 is an independent predictor of prognosis in chronic HF. Our findings suggest that HSP27 may improve risk-stratification in chronic HF beyond known prognostic predictors.