Hsp70 Content 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.

High temperature induces oxidative stress in spotted seabass (Lateolabrax maculatus) and leads to inflammation and apoptosis

Our study aims to examine the changes of long-term high temperature on the mortality and health status of spotted seabass (Lateolabrax maculatus), as well as to screen suitable biomarkers to determine whether the spotted seabass is under heat stress. In this study, 360 juvenile spotted seabass were evenly distributed into three temperature-controlled systems at 27 °C (N, normal temperature), 31 °C (M, moderate temperature), and 35 °C (H, high temperature) for an 8-week aquaculture experiment. The results revealed that 35 °C water temperature significantly increased the mortality and the MDA content in tissues (P < 0.05). Meanwhile, 35 °C water temperature significantly increased the activity of SOD enzyme and T-AOC capacity in tissues, as well as the expression of hsp60, hsp70, and hsp90 (P < 0.05). Additionally, the expression of nrf2, il1β, il8, caspase3, caspase9, and bax in the liver significantly increased (P < 0.05), while the expression of keap1, il10, tgfβ, and bcl2 decreased significantly (P < 0.05). These results indicate that 35 °C water temperature induces oxidative stress in spotted seabass, leading to tissue oxidative damage, promoting inflammation and apoptosis in liver, and increasing mortality. However, the organism compensates by heightening its antioxidant capacity via the Nrf2-Keap1 signaling pathway and inducing high expression of heat shock proteins for self-protection. Furthermore, the alterations in the mRNA level of hsp70 and MDA content in the liver, muscle, and kidney can serve as indicators for evaluating spotted seabass under prolonged heat stress.

Association between serum concentration of HSP-70, C-peptide, and VDBP with the pathogenesis of type 2 diabetes mellitus

Association between serum concentration of HSP-70, C-peptide, and VDBP with the pathogenesis of type 2 diabetes mellitus

Alleviating effect of methionine on intestinal mucosal injury induced by heat stress

Climate change is an increasing concern of stakeholders worldwide. The intestine is severely impacted by the heat stress. This study aimed to investigate the alleviating effects of methionine on the intestinal damage induced by heat stress in mice. The mice were divided into four groups: control group (C), methionine deficiency group (MD), methionine + heat stress group (MH), and methionine deficiency + heat stress group (MDH). Histopathological techniques, PAS-Alcian blue staining, immunohistochemistry method, biochemical quantification method, ELISA, and micro method were used to study the changes in the intestinal mucosal morphology, the number of goblet cells, the expression of tight junction proteins, the peroxide product contents and antioxidant enzyme activities, the intestinal mucosal damage, the content of immunoglobulins and HSP70, the activity of Na+/K+-ATPase. The results showed that methionine can improve intestinal mucosal morphology (increase the villi height, V/C value, and muscle layer thickness, decrease crypt depth), increase the expression of tight junction proteins (Claudin-1, Occludin, ZO-1) and the content of DAO, decrease the content of intestinal mucosa damage markers (ET, FABP2) and peroxidation products (MDA), increase the activity of antioxidant enzymes (GR, GSH-Px, SOD), the number of goblet cells, the contents of immunoglobulins (sIgA, IgA, IgG, IgM) and stress protein (HSP70), and the activity of Na+/K+-ATPase. It is suggested that methionine can alleviate intestinal damage in heat-stressed mice.

Characteristics of HIF-1Α and HSP70 MRNA Expression, Level, and Interleukins in Experimental Chronic Generalized Periodontitis.

Periodontal diseases are a rather complex problem of modern dentistry and do not have only medical but also social significance. The objective of this study is to weigh the effect of a mixture of Thiotriazoline and L-arginine (1:4) on the parameters of the system of endogenous cytoprotection of blood and periodontal illness in rats with experimental chronic generalized periodontitis and substantiate further study of this blend. The study aimed to evaluate the impact of a combination of Thiotriazoline and L-arginine (in a ratio of 1:4) on the parameters of the endogenous blood cytoprotection system and periodontium in rats with experimental chronic generalized periodontitis. A group of outbred rats weighing 190-220 g and sourced from the vivarium of the Institute of Pharmacology and Toxicology of the Academy of Medical Sciences of Ukraine were divided into four groups, each consisting of 10 animals. (1) Intact group, animals that were injected intragastrically with a solution of sodium chloride to chloride 0.9% for 30 days. (2) control, animals with experimental CGP who intragastrically sodium chloride solution 0.9% for 30 days. (3) animals with experimental CGP were injected intramuscularly with Thiotriazoline + L-arginine (1:4) in a dosage of 200 mg/kg (30 days). (4) animals with experimental CGP, for which daily intragastric reference drug Mexidol, in dosage 250 mg/kg (30 days). In this study, we utilized two substances: Thiotriazoline and L-arginine hydrochloride. The combination of Thiotriazoline and L-arginine (in a ratio of 1:4) was prepared at the Department of Pharmaceutical Chemistry of ZSMU. At the conclusion of the experiment, the rats were carefully removed from the study while under thiopental-sodium anesthesia, and administered at a dosage of 40 mg/kg. We have found that the administration of a combined preparation of Thiotriazoline with L-arginine to rats with CGP leads to a significant decrease in the blood concentration of pro-inflammatory cytokines IL-1b and TNF-a by 56.1% and 71%, respectively. The administration of Mexidol at a dosage of 250 mg/kg, as well as the combination of Thiotriazoline and Larginine in a ratio of 1:4 at a dosage of 200 mg/kg, resulted in a significant reduction in gingival pocket depth in animals with CGP. Specifically, the gingival pocket depth was reduced to 6 mm (p < 0.05) with Mexidol and further reduced to 4 mm (p < 0.05) with the combination of Thiotriazoline and L-arginine. Additionally, the animals exhibited minimal bleeding, swelling, and tooth mobility when treated with the combination of Thiotriazoline and L-arginine. The administration of a combination of Thiotriazoline and L-arginine (in a ratio of 1:4) at a dosage of 200 mg/kg to animals with CGP resulted in a noteworthy reduction in the blood concentration of pro-inflammatory cytokines IL-1b and TNF-a. Specifically, there was a significant decrease of 56.1% (p < 0.05) in IL-1b and 71% (p < 0.05) in TNF-a levels. The course administration of a combination of Thiotriazoline and L-arginine (1:4) (200 mg/kg) to animals with CGP led to an increased expression of HSP70 mRNA (p < 0.05) in the periodontium by 8.2 times and HIF-1a mRNA by 8.2 times. 2.8 times (p < 0.05) against the background of an increase in the blood concentration of HSP70 by 95% (p < 0.05). Also, in the periodontium of animals in this group, a decrease in the expression of c-Fos mRNA by 36.7% (p < 0.05) was found compared to the control group.

Prodromic Inflammatory-Oxidative Stress in Peritoneal Leukocytes of Triple-Transgenic Mice for Alzheimer's Disease.

Inflammatory-oxidative stress is known to be pivotal in the pathobiology of Alzheimer's disease (AD), but the involvement of this stress at the peripheral level in the disease's onset has been scarcely studied. This study investigated the pro-inflammatory profile and oxidative stress parameters in peritoneal leukocytes from female triple-transgenic mice for AD (3xTgAD) and non-transgenic mice (NTg). Peritoneal leukocytes were obtained at 2, 4, 6, 12, and 15 months of age. The concentrations of TNFα, INFγ, IL-1β, IL-2, IL-6, IL-17, and IL-10 released in cultures without stimuli and mitogen concanavalin A and lipopolysaccharide presence were measured. The concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), lipid peroxidation, and Hsp70 were also analyzed in the peritoneal cells. Our results showed that although there was a lower release of pro-inflammatory cytokines by 3xTgAD mice, this response was uncontrolled and overstimulated, especially at a prodromal stage at 2 months of age. In addition, there were lower concentrations of GSH in leukocytes from 3xTgAD and higher amounts of lipid peroxides at 2 and 4 months, as well as, at 6 months, a lower concentration of Hsp70. In conclusion, 3xTgAD mice show a worse pro-inflammatory response and higher oxidative stress than NTg mice during the prodromal stages, potentially supporting the idea that Alzheimer's disease could be a consequence of peripheral alteration in the leukocyte inflammation-oxidation state.

Eccentric muscle-damaging exercise in the heat lowers cellular stress prior to and immediately following future exertional heatexposure.

Muscle-damaging exercise (e.g., downhill running [DHR]) or heat exposure bouts potentially reduce physiological and/or cellular stress during future exertional heat exposure; however, the true extent of their combined preconditioning effects is unknown. Therefore, this study investigated the effect of muscle-damaging exercise in the heat on reducing physiological and cellular stress during future exertional heat exposure. Ten healthy males (mean±Standard Definition; age, 23±3years; body mass, 78.7±11.5kg; height, 176.9±4.7cm) completed this study. Participants were randomly assigned into two preconditioning groups: (a) DHR in the heat (ambient temperature [Tamb], 35°C; relative humidity [RH], 40%)and (b) DHR in thermoneutral (Tamb, 20°C; RH, 20%). Seven days following DHR, participants performed a 45-minflat run in the heat (FlatHEAT [Tamb, 35°C; RH, 40%]). During exercise, heart rate and rectal temperature (Trec) were recorded at baseline and every 5-min. Peripheral blood mononuclear cells were isolated to assess heat shock protein 72 (Hsp72) concentration between conditions at baseline, immediately post-DHR, and immediately pre-FlatHEAT and post-FlatHEAT. Mean Trec during FlatHEAT between hot (38.23±0.38°C) and thermoneutral DHR (38.26±0.38°C) was not significantly different (P=0.68), with no mean heart rate differences during FlatHEAT between hot (172±15beatsmin-1) and thermoneutral conditions (174±8beatsmin-1; P=0.58). Hsp72 concentration change from baseline to immediately pre-FlatHEAT was significantly lower in hot (-51.4%) compared to thermoneutral (+24.2%; P=0.025) DHR, with Hsp72 change from baseline to immediately post-FlatHEAT also lower in hot (-52.6%) compared to thermoneutral conditions (+26.3%; P=0.047). A bout of muscle-damaging exercise in the heat reduces cellular stress levels prior to and immediately following future exertional heat exposure.

Serum heat shock protein concentrations are not associated with amyotrophic lateral sclerosis risk or survival in three European populations

Introduction: Serum heat shock protein (HSP) concentrations have been reported as potential biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigate the role of serum HSP70, HSP90, and DNAJC7 as biomarkers for ALS. Methods: Serum samples were collected from ALS patients and volunteer controls from three different clinical cohorts (in Germany, Ireland, and Italy). Serum HSP concentrations were determined using enzyme-linked immunosorbent assay. Descriptive statistics, generalized logistic regression, and Cox proportional hazards models were used to model associations between log serum HSP concentrations and ALS risk. Results: In total, 251 ALS patients and 184 healthy volunteers were included. Logistic regression models failed to find associations between ALS risk and log serum concentration of HSP70 (OR 0.43, 95% CI: 0.10–1.78, p = 0.242), HSP90 (OR 0.95, 95% CI: 0.39–2.37, p = 0.904), or DNAJC7 (OR 1.55, 95% CI: 0.90–2.68, p = 0.118). Survival of ALS patients was not associated with log serum concentration of HSP HSP70 (HR1.06, 95% CI: 0.36–3.14, p = 0.916), HSP90 (HR 1.17, 95% CI: 0.67–2.02, p = 0.584), or DNAJC7 (HR 0.83, 95% CI: 0.57–1.21, p = 0.337). Discussion: We did not replicate previous findings that serum HSP70 and HSP90 concentrations were associated with risk of ALS. DNAJC7 was not associated with ALS risk, and there were no obvious longitudinal patterns in log serum concentrations of HSP70, HSP90, or DNAJC7. In addition, serum HSP concentrations were not associated with ALS survival.

Maternal and Umbilical Cord Heat-Shock Protein 70 Levels in Patients with Gestational Diabetes Mellitus

AIMS: The purpose of this study is to determine if heat shock protein 70 (Hsp-70), a marker of cellular stress, is elevated in maternal serum and umbilical cord in pregnancies complicated by gestational diabetes mellitus (GDM) and to determine whether altered serum Hsp-70 concentrations in umbilical cord are related to serve as an indicator of early term delivery (37 0/7–38 6/7 weeks of gestation) in women with GDM and control group. METHODS: The study included 62 patients with GDM (GDM group) and 22 non-diabetic, healthy women before caesarean section in this case-control study. We analyzed serum levels of Hsp-70 in pregnancies and umbilical cord sera and other biochemical and anthropometric markers, early term delivery in all subjects. RESULTS: Maternal Serum levels of Hsp-70 were significantly higher in patients with GDM than in healthy pregnant women. The umbilical cord levels of Hsp-70 in GDM patients were also increased as compared to healthy pregnant women but missed the commonly acceptable significance level. Cord Hsp-70 levels showed a negatively significant correlation with time of delivery, in women with GDM patients. Cord Hsp-70 levels showed a negatively significant correlation with time of delivery, also in the whole group. CONCLUSIONS: Maternal Hsp-70 was significantly higher in patients with GDM. The obtained results seem to indicate that elevated umbilical cord Hsp-70 values may potentially be used as indicators of risk factor for early term delivery in pregnancies.

Skeletal Muscle Heat Shock Protein Content and the Repeated Bout Effect.

The "Repeated Bout Effect" (RBE) occurs when a skeletal muscle is preconditioned with a few lengthening contractions (LC) prior to exposing the muscle to a greater number of LC. The preconditioning (PC) results in significantly less damage and preservation of force. Since it takes only a few LC to increase muscle heat shock protein (HSP) content, it was of interest to examine the relationship between HSPs and the RBE. To do this, one tibialis anterior (TA) muscle from Sprague-Dawley rats (n = 5/group) was preconditioned with either 0, 5, or 15 lengthening contractions (LC) and exposed to a treatment of 60 LC 48 h later. Preconditioning TA muscles with 15 LC, but not 5 LC, significantly elevated muscle αB-crystallin (p < 0.05), HSP25 (p < 0.05), and HSP72 content (p < 0.001). These preconditioned TA muscles also showed a significantly (p < 0.05) reduced loss of active torque throughout the subsequent 60 LC. While there was a trend for all preconditioned muscles to maintain higher peak torque levels throughout the 60 LC, no significant differences were detected between the groups. Morphologically, preconditioned muscles appeared to show less discernible muscle fiber damage. In conclusion, an elevated skeletal muscle HSP content from preconditioning may contribute to the RBE.

Comparative Assessment of the Effectiveness of HSP70 / HIF-1α System Modulators after Prenatal Hypoxia

Prenatal hypoxia (PH) poses a significant threat to fetal development and may be responsible for neonatal mortality or neurodevelopmental abnormalities. The proteins HSP70 and HIF-1, which hold a distinct significance in the cellular reaction to PH, can be regarded as potential targets for pharmaceutical interventions aimed at mitigating the repercussions of chronic PH. This study aimed to identify a possible correlation between offspring survival and stages of expression of endogenous neuroprotective factors (HSP70 and HIF-1) after chronic prenatal hypoxia with course administration of potential HSP70 modulators (angiolin, piracetam, thiotriazoline, nicomex, cerebrocurin, tamoxifen, L-arginine, glutoredoxin, HSF-1, and mildronate). In the rat offspring after PH we determined the plasma concentrations of HSP70 and HIF-1 by solid-phase ELISA immunoassay, and the expression of HIF-1 mRNA and HSP70 mRNA by real-time PCR. For the first time, we found a positive correlation between offspring survival after PH and the expression of HIF-1 and HSP70, both in groups without experimental therapy and in groups receiving pharmacological agents. The course administration of HSP70/HIF-1α modulators, especially angiolin (50 mg/kg), cerebrocurin (150 mg/kg), and HSF-1 (50 mg/kg), to rats that underwent PH reduces postnatal lethality, increases blood plasma concentrations of HSP70 and HIF-1α, and positively affects the expression level of HIF-1α mRNA in the rat brain. These drugs can be considered as the most promising drug candidates for new therapeutic strategies of pharmacological correction of the consequences of chronic PH.

Betaine addition to the diet alleviates intestinal injury in growing rabbits during the summer heat through the AAT/mTOR pathway

BackgroundThe aim of this experiment was to investigate the effect of different levels of betaine (Bet) inclusion in the diet on the intestinal health of growing rabbits under summer heat. A total of 100 weaned Qixing meat rabbits aged 35 d with body weight of 748.61 ± 38.59 g were randomly divided into 5 treatment groups: control group (basal diet) and Bet groups (basal diet + 0.75, 1.0, 1.5 or 2.0 g/kg Bet). The average daily temperature in the rabbitry during the experiment was 30.48 °C and the relative humidity was 69.44%.ResultsDietary addition of Bet had no significant effect on growth performance and health status of growing rabbits (P > 0.05), but it increased ileal secretory immunoglobulin A content compared to the control under summer heat (P < 0.05). Addition of 0.75 g/kg Bet up-regulated jejunal IL-4, down-regulated ileal TNF-α expression (P < 0.05). The addition of 1.0 g/kg Bet increased the villi height (VH) in the jejunum (P < 0.05). Serum glucose levels were reduced, and the expression of SLC6A20 was up-regulated in jejunum and ileum of rabbits fed with 1.5 g/kg Bet (P < 0.05). When added at 2.0 g/kg, Bet reduced serum HSP70 content, increased jejunal VH, and up-regulated duodenal SLC7A6, SLC38A2, mTOR and 4EBP-2 expression (P < 0.05). Correlation analysis revealed that intestinal mTOR expression was significantly and positively correlated with SLC7A6, SLC38A2, SLC36A1 and IL-4 expression (P < 0.05).ConclusionsDietary addition of Bet can up-regulate the expression of anti-inflammatory factors through the AAT/mTOR pathway, improve the intestinal immune function, alleviate intestinal damage in growing rabbits caused by summer heat, and improve intestinal health.

Analyses and Utilization of Selectively Tuned Human Adipose-Derived Stromal/Stem Cell Exosomes.

We have developed a hollow fiber bioreactor-based production system for manufacturing large quantities of extracellular vesicles (EVs) containing exosomes from adult human adipose-derived stromal/stem cells (ASCs). By manipulating the cellular bioreactor environment, we have found that we can alter ASC EV production, secretion, and surface protein composition. The aims of this chapter are to describe the methodology for culturing and tuning of adipose ASCs in a bioreactor, along with the collection and isolation of the EVs containing exosomes demonstrating increased HSP70 content.

What is in common between preeclampsia, HPS70 and medieval headwear? Part I. Serum HPS70 in preeclampsia: systematic review and meta-analysis

The objective: to investigate the relationship between HSP70 concentrations in maternal serum and preeclampsia and assess the prospects of using HSP70 as a preeclampsia predictor.Materials and methods. The original publications, which study HSP70 in maternal serum of preeclamptic women, were searched and analyzed. Papers were identified with Scopus, PubMed Central, Virtual Health Library databases, published before January 2023, the keywords were «HSP70», «preeclampsia», «heat shock protein 70», «pregnant». Statistical analysis was performed via software EZR 1.55.Results. 16 case-control studies were included, making a total of 751 pregnant women with preeclampsia and 719 healthy pregnant women. The analysis found the statistically significant difference between HSP70 concentrations in maternal serum of preeclamptic and healthy pregnant patients. Cochrane Q-test showed high heterogeneity among studies (p&lt;0.01), the value of the І2 statistic was 97%. Dividing the studies into groups made it possible to reduce or remove heterogeneity completely. This high level of heterogeneity for publications together, but low within most groups, suggests that there are certain factors that significantly influence some studies.Conclusions. The conducted systematic review and meta-analysis confidently indicate an increased average serum concentration of HSP70 in pregnant women with preeclampsia compared to healthy pregnant women at the corresponding gestational age.No statistically significant relationship was found between increased HSP70 concentration in preeclampsia and pregnant women’s age, gestational age, systolic and diastolic blood pressure. Quantitative assessment of HSP70 levels is complicated by the lack of a single standard for laboratory diagnostics. The case-control design of the presented studies limits their significance.The use of HSP70 as a predictor of preeclampsia is promising, but requires further study and prospective cohort studies.

Extracellular heat shock protein 70 levels in tumour-bearing dogs and cats treated with radiation therapy and hyperthermia.

Hyperthermia is a form of a cancer treatment which is frequently applied in combination with radiotherapy (RT) to improve therapy responses and radiosensitivity. The mode of action of hyperthermia is multifactorial; the one hand by altering the amount of the blood circulation in the treated tissue, on the other hand by modulating molecular pathways involved in cell survival processes and immunogenic interactions. One of the most dominant proteins induced by hyperthermia is the major stress-inducible heat shock protein 70 (Hsp70). Hsp70 can be found in the blood either as a free-protein (free HSP70) derived from necrotic cells, or lipid-bound (liposomal Hsp70) when it is actively released in extracellular vesicles (EVs) by living cells. The aim of the study was to evaluate the levels of free and liposomal Hsp70 before and after treatment with RT alone or hyperthermia combined with radiotherapy (HTRT) in dogs and cats to evaluate therapy responses. Peripheral blood was collected from feline and canine patients before and at 2, 4, 6 and 24 h after treatment with RT or HTRT. Hsp70 enzyme-linked immunosorbent assays (ELISAs) were performed to determine the free and liposomal Hsp70 concentrations in the serum. The levels were analysed after the first fraction of radiation to study immediate effects and after all applied fractions to study cumulative effects. The levels of free and liposomal Hsp70 levels in the circulation were not affected by the first singular treatment and cumulative effects of RT in cats however, after finalizing all treatment cycles with HTRT free and liposomal Hsp70 levels significantly increased. In dogs, HTRT, but not treatment with RT alone, significantly affected liposomal Hsp70 levels during the first fraction. Free Hsp70 levels were significantly increased after RT, but not HTRT, during the first fraction in dogs. In dogs, on the other hand, RT alone resulted in a significant increase in liposomal Hsp70, but HTRT did not significantly affect the liposomal Hsp70 when cumulative effects were analysed. Free Hsp70 was significantly induced in dogs after both, RT and HTRT when cumulative effects were analysed. RT and HTRT treatments differentially affect the levels of free and liposomal Hsp70 in dogs and cats. Both forms of Hsp70 could potentially be further investigated as potential liquid biopsy markers to study responses to RT and HTRT treatment in companion animals.

The Role of Hyperthermia in Potentiation of Anti-Angiogenic Effect of Cisplatin and Resveratrol in Mice Bearing Solid Form of Ehrlich Ascites Tumour

The aim of this study was to investigate the therapeutic potential of resveratrol in combination with cisplatin on the inhibition of tumour angiogenesis, growth, and macrophage polarization in mice bearing the solid form of an Ehrlich ascites tumour (EAT) that were exposed to whole-body hyperthermia treatment. In addition, we investigated whether a multimodal approach with hyperthermia and resveratrol could abolish cisplatin resistance in tumour cells through the modulation of histone deacetylase (HDAC) activity and levels of heat shock proteins (HSP70/HSP90) and contribute to the direct toxicity of cisplatin on tumour cells. The tumour was induced by injecting 1 × 106 EAT cells subcutaneously (sc) into the thighs of Balb/c mice. The mice were treated with resveratrol per os for five consecutive days beginning on day 2 after tumour injection and/or by injecting cisplatin intraperitoneally (ip) at a dose of 2.5 mg/kg on days 10 and 12 and at a dose of 5 mg/kg on day 15. Immediately thereafter, the mice were exposed to systemic hyperthermia for 15 min at a temperature of 41 °C. The obtained results showed that the administration of resveratrol did not significantly contribute to the antitumour effect of cisplatin and hyperthermia, but it partially contributed to the immunomodulatory effect and to the reduction of cisplatin toxicity and to a slight increase in animal survival. This treatment schedule did not affect microvessel density, but it inhibited tumour growth and modulated macrophage polarization to the M1 phenotype. Furthermore, it abolished the resistance of tumour cells to cisplatin by modulating HDAC activity and the concentration of HSP70 and HSP90 chaperones, contributing to the increased lifespan of mice. However, the precise mechanism of the interaction between resveratrol, cisplatin, and hyperthermia needs to be investigated further.

Seasonal influence on expression of heat shock proteins (HSP70 and HSP90) vis-à-vis functional competence of Gir bull semen

The success of assisted reproduction relies on functional competence of frozen-thawed semen. Heat stress affects protein folding leading to aggregation of mis-folded proteins. Hence, a total of 384 (32 ejaculates/bull/season) ejaculates from six matured Gir bulls were used to evaluate physico-morphological parameters, the expression of HSPs (70 and 90) and fertility of frozen-thawed semen. The mean percent individual motility, viability and membrane integrity were significantly (p < 0.01) higher in winter compared to summer. Out of 1200 Gir cows inseminated, 626 confirmed pregnant and the mean conception rate of winter (55.04 ± 0.35) was significantly (p < 0.001) higher than summer (49.33 ± 0.32). A significant (p < 0.01) difference in concentration of HSP70 (ng/mg of protein) but not HSP90was observed between the two seasons. The HSP70 expression in pre-freeze semen of Gir bulls had significant positive correlation with motility (p < 0.01, r = 0.463), viability (p < 0.01, r = 0.565), acrosome integrity (p < 0.05, r = 0.330) and conception rate (p < 0.01, r = 0.431). In conclusion, the season influences physico-morphological parameters and expression of HSP70 but not HSP90 in Gir bull semen. The HSP70 expression is positively correlated with motility, viability, acrosome integrity and fertility of semen. The semen expression of HSP70 may be utilized as biomarker for thermo-tolerance, semen quality and fertilizing capacity of Gir bull semen.

Protective effect of dietary dandelion (Taraxacum officinale) extract on common carp under acute ammonia stress

This study examined the remedial effect of dandelion extract (DE) on acute ammonia stress in common carp. The experiment involved supplementing the common carp diet with five DE dozes, including 0 (control), 2%, 4%, 6%, and 8% DE to the basic feed for 56 days. Then, all the fish were exposed to semile thal ammonia stress (1.65 mg/L) for 96 h, followed by detections the indexes of mortality, blood biochemistry, antioxidation, immunity, stress, and inflammation. The results showed that dietary DE increased the serum protein content and antioxidant enzyme activity of common carp ( P < 0.05). However, DE did not significantly affect the contents of stress hormone, HSP70 and HSP90 (p > 0.05). Exposure to ammonia significantly decreased the activities of immune and antioxidant enzymes in the control group. The serum protein content and immune enzyme activity of each DE group were significantly higher than the control group. After ammonia exposure, IL-1β, IL-6, IL-8, TNF-α, and IFN-γ activities in DE groups were significantly lower then the Ctrl group，and IL-10 and antioxidant enzyme activities in 4% DE, 6% DE, and 8% DE groups was significantly higher compared to the Ctrl ( P < 0.05). Ammonia stress caused pathological damage to the liver tissue in control, 2% DE, 4% DE, and 8% DE groups, but the liver tissue of the 6% DE group showed normal tissue characteristics. Therefore, DE has a protective effect on common carp under acute ammonia exposure. Optimal doses of DE can improve the survival rate, antioxidant capacity, and nonspecific immunity, while can reduce the stress and inflammatory reaction of common carp caused by acute ammonia exposure. The second-order multiple regression analysis of TP, COR, LZM, T-AOC, mortality, and immune protection after ammonia stress showed 4.62–6.82% as the optimal level of dietary DE supplementation for carp under acute ammonia stress.

Circulating Hsp70 Levels and the Immunophenotype of Peripheral Blood Lymphocytes as Potential Biomarkers for Advanced Lung Cancer and Therapy Failure after Surgery.

Lung cancer remains a devastating disease with a poor clinical outcome. A biomarker signature which could distinguish lung cancer from metastatic disease and detect therapeutic failure would significantly improve patient management and allow for individualized, risk-adjusted therapeutic decisions. In this study, circulating Hsp70 levels were measured using ELISA, and the immunophenotype of the peripheral blood lymphocytes were measured using multiparameter flow cytometry, to identify a predictive biomarker signature for lung cancer patients pre- and post-operatively, in patients with lung metastases and in patients with COPD as an inflammatory lung disease. The lowest Hsp70 concentrations were found in the healthy controls followed by the patients with advanced COPD. Hsp70 levels sequentially increased with an advancing tumor stage and metastatic disease. In the early-recurrence patients, Hsp70 levels started to increase within the first three months after surgery, but remained unaltered in the recurrence-free patients. An early recurrence was associated with a significant drop in B cells and an increase in Tregs, whereas the recurrence-free patients had elevated T and NK cell levels. We conclude that circulating Hsp70 concentrations might have the potential to distinguish lung cancer from metastatic disease, and might be able to predict an advanced tumor stage and early recurrence in lung cancer patients. Further studies with larger patient cohorts and longer follow-up periods are needed to validate Hsp70 and immunophenotypic profiles as predictive biomarker signatures.

The persistence of stress-induced physical inactivity in rats: an investigation of central monoamine neurotransmitters and skeletal muscle oxidative stress.

Sedentary lifestyles have reached epidemic proportions world-wide. A growing body of literature suggests that exposures to adverse experiences (e.g., psychological traumas) are a significant risk factor for the development of physically inactive lifestyles. However, the biological mechanisms linking prior stress exposure and persistent deficits in physical activity engagement remains poorly understood. The purpose of this study was twofold. First, to identify acute stress intensity thresholds that elicit long-term wheel running deficits in rats. To that end, young adult male rats were exposed to a single episode of 0, 50, or 100 uncontrollable tail shocks and then given free access to running wheels for 9 weeks. Second, to identify stress-induced changes to central monoamine neurotransmitters and peripheral muscle physiology that may be maladaptive to exercise output. For this study, rats were either exposed to a single episode of uncontrollable tail shocks (stress) or left undisturbed in home cages (unstressed). Eight days later, monoamine-related neurochemicals were quantified by ultra-high performance liquid chromatography (UHPLC) across brain reward, motor, and emotion structures immediately following a bout of graded treadmill exercise controlled for duration and intensity. Additionally, protein markers of oxidative stress, inflammation, and metabolic activity were assessed in the gastrocnemius muscle by Western blot. For experiment 1, stress exposure caused a shock number-dependent two to fourfold decrease in wheel running distance across the entire duration of the study. For experiment 2, stress exposure curbed an exercise-induced increase of dopamine (DA) turnover measures in the prefrontal cortex and hippocampus, and augmented serotonin (5HT) turnover in the hypothalamus and remaining cortical area. However, stress exposure also caused several monoaminergic changes independent of exercise that could underlie impaired motivation for physical activity, including a mild dopamine deficiency in the striatal area. Finally, stress potently increased HSP70 and lowered SOD2 protein concentrations in the gastrocnemius muscle, which may indicate prolonged oxidative stress. These data support some of the possible central and peripheral mechanisms by which exposure to adverse experiences may chronically impair physical activity engagement.