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Aquatic organisms are frequently exposed to various environmental stressors. Thus, the effects of high temperatures and herbicides on aquatic organisms are a major subject of interest. In this study, we studied the effects of short-term exposure (1 week) to Roundup®, a glyphosate-based herbicide (concentrations: 0.5 and 5 µg/L), on the morphology of gills, digestive glands, and connective tissues, and the expression of heat shock protein-70 (HSP70, a chaperone protein), cytochrome P450 (CYP450, a biomarker of environmental contaminants), dinitrophenyl protein (DNP, a biomarker of protein oxidation), nitrotyrosine protein (NTP, a biomarker of protein nitration), antioxidant enzymes such as superoxidase dismutase (SOD) and catalase (CAT) in tissues of American oyster, Crassostrea virginica (Gmelin, 1791) maintained at high temperature (30 °C). Histological analyses showed an increase in mucous production in the gills and digestive glands, and in hemocyte aggregation in the connective tissues as well as a structural change of lumen in the digestive glands of oysters exposed to Roundup. Immunohistochemical and quantitative RT-PCR analyses showed significant (P < 0.05) increases in HSP70, CYP450, DNP, NTP, CAT, and SOD mRNA and protein expressions in the tissues of oysters exposed to Roundup. Taken together, these results suggest that exposure to Roundup at high temperature induces overproduction of reactive oxygen species/reactive nitrogen species which in turn leads to altered prooxidant-antioxidant activity in oyster tissues. Moreover, our results provide new information on protein oxidation/nitration and antioxidant-dependent mechanisms for HSP70 and CYP450 regulations in oysters exposed to Roundup at high temperature. [ABSTRACT FROM AUTHOR]

Experiments were performed to determine the effect of ergothioneine on rectal temperature and the serum concentrations of heat shock protein-70 (HSP-70) and tumor necrosis factor-α (TNF-α) in stallions following a race of 2000 m in a hot-dry environment. Eighteen stallions weighing approximately 400 kg each were used for the experiment. They were divided into three groups of six stallions each. Group I (EEX) was the experimental group that was administered ergothioneine (0.5 mg/kg per os), while group II (EEC) did not receive ergothioneine before exercise. The third group (EEN) was neither administered ergothioneine nor exercised. The dry-bulb temperature and the relative humidity of the experiment were determined for six days and on the day of the experiment. The temperature-humidity index was also calculated. Rectal temperature, serum HSP-70, and TNF-α concentrations of all horses were measured before commencement, immediately after, and 2 h after the exercise. The dry-bulb temperature and relative humidity which showed diurnal fluctuations increased significantly (p < 0.05) between 06.00 h and 12.00 h (22.6 ± 1.23 and 38.6 ± 6.5, respectively). Serum TNF-α and HSP-70 levels of the stallions in the EEX group were higher than the values obtained in the EEC and EEN groups (p < 0.05). The values of rectal temperature obtained were lower (p < 0.05) in the EEX group than in the other groups. Therefore, it could be concluded that ergothioneine modulated rectal temperature, as well as TNF-α and HSP-70 concentrations in the stallions, and might be beneficial to horses during exercise.

Enhanced heat shock protein-70 (HSP-70) expression in the lungs is associated with attenuated acute lung injury (ALI) in a sepsis model. Chronic kidney disease (CKD) significantly contributes to the poor prognosis of patients with sepsis. This study examined the relationship between sepsis-induced ALI severity and altered lung HSP-70 expression in CKD. Experimental rats underwent a sham operation (control group) or 5/6 nephrectomy (CKD group). Sepsis was induced with cecal ligation and puncture (CLP). Laboratory tests and lung harvest were performed in the control group (without CLP and after 3, 12, 24, and 72 h of CLP) and in the CKD group (without CLP and after 72 h of CLP). ALI was the most severe after 12 h of sepsis. The mean lung injury score at 72 h after sepsis was significantly higher in the CKD group than in the control group (4.38 versus 3.30, p < 0.01). Nonetheless, enhanced lung HSP-70 expression was not observed in the CKD group. This study shows that altered lung HSP-70 expression is associated with the worsening of sepsis-induced ALI in patients with CKD. Enhancing lung HSP-70 is a novel treatment target for patients with CKD and sepsis-induced ALI. [ABSTRACT FROM AUTHOR]

Nimbolide is an active constituent of Azadirachta indica and is known for its anti‐inflammatory, anti‐oxidant, immune‐modulatory, and anti‐cancer effects. Few studies suggest that nimbolide treatment influences the responses to rheumatoid arthritis, but the underlying molecular mechanisms involved are not yet well established. Therefore, the present study was designed to determine the effect of nimbolide on expression regulation of toll‐like receptors to attenuate rheumatoid arthritis. The rheumatoid arthritis model was established by injecting complete Freund's adjuvant (CFA) intra‐dermally into the sub‐plantar region of the left hind paw of rats. Nimbolide (20 mg/kg) and piroxicam (10 mg/kg) were given to arthritic rats. Rats treated with nimbolide showed a significant reduction in inflammatory cells, rheumatoid factor, ESR, and improved the body weight. The results indicated that nimbolide possesses the capacity to attenuate rheumatoid arthritis by downregulating toll‐like receptors, IL‐17, IL‐23, HSP70, and IFN‐γ expression levels. Nimbolide treatment showed significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to piroxicam, which is a standard non‐steroidal anti‐inflammatory drug used for the treatment of rheumatoid arthritis. It can be concluded that nimbolide can be considered as a potential candidate for therapeutic targeting of the toll‐like receptors pathway in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Experiments were performed to determine the effect of ergothioneine on rectal temperature and the serum concentrations of heat shock protein-70 (HSP-70) and tumor necrosis factor-a (TNF-a) in stallions following a race of 2000 m in a hot-dry environment. Eighteen stallions weighing approximately 400 kg each were used for the experiment. They were divided into three groups of six stallions each. Group I (EEX) was the experimental group that was administered ergothioneine (0.5 mg/kg per os), while group II (EEC) did not receive ergothioneine before exercise. The third group (EEN) was neither administered ergothioneine nor exercised. The dry-bulb temperature and the relative humidity of the experiment were determined for six days and on the day of the experiment. The temperature-humidity index was also calculated. Rectal temperature, serum HSP-70, and TNF-a concentrations of all horses were measured before commencement, immediately after, and 2 h after the exercise. The dry-bulb temperature and relative humidity which showed diurnal fluctuations increased significantly (p < 0.05) between 06.00 h and 12.00 h (22.6 ± 1.23 and 38.6 ± 6.5, respectively). Serum TNF-a and HSP-70 levels of the stallions in the EEX group were higher than the values obtained in the EEC and EEN groups (p < 0.05). The values of rectal temperature obtained were lower (p < 0.05) in the EEX group than in the other groups. Therefore, it could be concluded that ergothioneine modulated rectal temperature, as well as TNF-a and HSP-70 concentrations in the stallions, and might be beneficial to horses during exercise. [ABSTRACT FROM AUTHOR]

Abstract Background The heat shock protein-70 (HSP70) is a protein associated with response and adaptation to stress, as well as protection of the cells against thermal and oxidative stress in animals. It is an evolutionarily conserved protein, but its expression has been reportedly varied. Therefore, this study implemented computational analyses of the amino acid sequences of this gene for a better understanding of the evolutionary and protein interactions variations associated with the gene to facilitate its exploitation for the breeding of animals with increasing adaptation to heat stress. Results The result showed that there is a wide evolutionary distance between humans and the selected farm animals studied but elegans shared a common evolutionary relationship with the farm animals. The sequence identity analysis returned exact matches among the sequences as minimum = 8.09%, maximum = 98.58%, and mean ± SD = 71.03 ± 26.3% across all the species, while the sequence similarities resemblance among the sequences were minimum = 16.49%, maximum = 100%, and mean ± SD = 78.99 ± 24.39%. The global block substitution matrix (BLOSUM62) analysis returned minimum = 0.18, maximum = 0.98, and mean ± SD = 0.62 ± 0.34. The analysis of the molecular weight of the protein sequences returned minimum = 5.70 kDa, maximum = 6.41 kDa, mean = 6.28 kDa, and standard deviation 0.17 kDa, and the isoelectric point of the protein sequences was minimum = 4.55, maximum = 7.17, mean = 5.56, and standard deviation = 0.65 while the hydrophobicity of the protein sequences were minimum = 45.20 kcal/mol, maximum = 53.02 kcal/mol, mean = 47.81 kcal/mol, and standard deviation = 1.85 kcal/mol. Conclusion The outcomes of the computational analyses led to the conclusion that variations exist in the conservations of amino acid residues of the gene in the studied farm and non-farm animals, and this is responsible for the differences and similarities in the expression of the HSP70 gene in different animals. It was also concluded that elegans are suitable model that could be exploited for a better understanding of response and adaptation to heat stress in duck, chicken, cattle, sheep, and goat when focusing on regulation and expression of heat shock protein gene 70 (HSP70).

Exposure to high ambient temperature is a stressor that influences both biological and behavioral functions and has been previously shown to have an extensive impact on brain structure and function. Physiological, cellular and behavioral responses to heat-stress (HS) (40–41 °C, 2 h) were evaluated in adult male Sprague-Dawley rats. The effect of HS exposure before predator-scent stress (PSS) exposure (i.e., HS preconditioning) was examined. Finally, a possible mechanism of HS-preconditioning to PSS was investigated. Immunohistochemical analyses of chosen cellular markers were performed in the hippocampus and in the hypothalamic paraventricular nucleus (PVN). Plasma corticosterone levels were evaluated, and the behavioral assessment included the elevated plus-maze (EPM) and the acoustic startle response (ASR) paradigms. Endogenous levels of heat shock protein (HSP)-70 were manipulated using an amino acid (L-glutamine) and a pharmacological agent (Doxazosin). A single exposure to an acute HS resulted in decreased body mass (BM), increased body temperature and increased corticosterone levels. Additionally, extensive cellular, but not behavioral changes were noted. HS-preconditioning provided behavioral resiliency to anxiety-like behavior associated with PSS, possibly through the induction of HSP-70. Targeting of HSP-70 is an attractive strategy for stress-related psychopathology treatment. [ABSTRACT FROM AUTHOR]

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Background: The heat shock protein-70 (HSP70) is a protein associated with response and adaptation to stress, as well as protection of the cells against thermal and oxidative stress in animals. It is an evolutionarily conserved protein, but its expression has been reportedly varied. Therefore, this study implemented computational analyses of the amino acid sequences of this gene for a better understanding of the evolutionary and protein interactions variations associated with the gene to facilitate its exploitation for the breeding of animals with increasing adaptation to heat stress. Results: The result showed that there is a wide evolutionary distance between humans and the selected farm animals studied but elegans shared a common evolutionary relationship with the farm animals. The sequence identity analysis returned exact matches among the sequences as minimum = 8.09%, maximum = 98.58%, and mean ± SD = 71.03 ± 26.3% across all the species, while the sequence similarities resemblance among the sequences were minimum = 16.49%, maximum = 100%, and mean ± SD = 78.99 ± 24.39%. The global block substitution matrix (BLOSUM62) analysis returned minimum = 0.18, maximum = 0.98, and mean ± SD = 0.62 ± 0.34. The analysis of the molecular weight of the protein sequences returned minimum = 5.70 kDa, maximum = 6.41 kDa, mean = 6.28 kDa, and standard deviation 0.17 kDa, and the isoelectric point of the protein sequences was minimum = 4.55, maximum = 7.17, mean = 5.56, and standard deviation = 0.65 while the hydrophobicity of the protein sequences were minimum = 45.20 kcal/mol, maximum = 53.02 kcal/mol, mean = 47.81 kcal/mol, and standard deviation = 1.85 kcal/mol. Conclusion: The outcomes of the computational analyses led to the conclusion that variations exist in the conservations of amino acid residues of the gene in the studied farm and non-farm animals, and this is responsible for the differences and similarities in the expression of the HSP70 gene in different animals. It was also concluded that elegans are suitable model that could be exploited for a better understanding of response and adaptation to heat stress in duck, chicken, cattle, sheep, and goat when focusing on regulation and expression of heat shock protein gene 70 (HSP70). [ABSTRACT FROM AUTHOR]

Background: Heat shock protein-70 (Hsp-70) exhibits cytoprotective effects against oxidative stress-induced airway injury. This study aimed to examine Hsp-70 and 8-hydroxy-2′-deoxyguanosine (8-OHdG) from tracheal aspirates (TA) in very low-birth weight (VLBW) preterm infants to predict the development of bronchopulmonary dysplasia (BPD).Methods: This birth cohort study enrolled 109 VLBW preterm infants, including 32 infants who developed BPD. Hsp-70 and 8-OHdG concentrations from TA were measured by immunoassay. The apoptosis of TA epithelial cells obtained on Day 28 after birth was measured using annexin-V staining assay.Results: Hsp-70 and 8-OHdG levels in TA fluid were persistently increased from Day 1 to Day 28 of life in the BPD group. Multiple linear regression analysis demonstrated that BPD was significantly associated with gestational age, respiratory distress syndrome, and TA Hsp-70 and 8-OHdG levels on post-natal Day 28. The TA Hsp-70 level positively correlated with TA 8-OHdG level on the Day 1 (r = 0.47) and Day 28 of life (r = 0.68). Incubation of recombinant Hsp-70 with primary epithelial cells derived from TA of patients decreased hydrogen peroxide-induced epithelial cell death.Conclusions: Hsp-70 levels are associated with a state of oxidative injury in the development of BPD.

(1) Background: Identifying early pancreas parenchymal changes remains a challenging radiologic diagnostic task. In this study, we hypothesized that applying artificial intelligence (AI) to contrast-enhanced ultrasound (CEUS) along with measurement of Heat Shock Protein (HSP)-70 levels could improve detection of early pancreatic necrosis in acute pancreatitis. (2) Methods: Acute pancreatitis (n = 146) and age- and sex matched healthy controls (n = 50) were enrolled in the study. The severity of acute pancreatitis was determined according to the revised Atlanta classification. The selected severe acute pancreatitis (AP) patient and an age/sex-matched healthy control were analysed for the algorithm initiation. Peripheral blood samples from the pancreatitis patient were collected on admission and HSP-70 levels were measured using ELISA. A CEUS device acquired multiple mechanical index contrast-specific mode images. Manual contour selection of the two-dimensional (2D) spatial region of interest (ROI) followed by calculations of the set of quantitative parameters. Image processing calculations and extraction of quantitative parameters from the CEUS diagnostic images were performed using algorithms implemented in the MATLAB software. (3) Results: Serum HSP-70 levels were 100.246 ng/ml (mean 76.4 ng/ml) at the time of the acute pancreatitis diagnosis. The CEUS Peek value was higher (155.5) and the mean transit time was longer (40.1 s) for healthy pancreas than in parenchyma affected by necrosis (46.5 and 34.6 s, respectively). (4) Conclusions: The extracted quantitative parameters and HSP-70 biochemical changes are suitable to be used further for AI-based classification of pancreas pathology cases and automatic estimation of pancreatic necrosis in AP. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis. Aim and Objectives: The aim of this study was to map the level of HSP-70 in vitiligo lesions to declare its role in the pathogenesis and activity of vitiligo. Materials and Methods: The study included thirty patients with vitiligo and 30 age- and sex-matched healthy controls. Vitiligo patients were divided as regards to the disease activity into highly active, moderately active, and inactive vitiligo groups. Skin biopsies were taken from the lesional and nonlesional skin of patients and from the normal skin of the controls. HSP-70 messenger RNA (mRNA) expression was estimated using quantitative real-time polymerase chain reaction. Results: Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease. Conclusions: HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease.

Background: Our recent research showed that resistin has a neuroprotective effect against stroke-induced injury through suppressing apoptosis and oxidative stress. However, the molecular mechanism of neuroprotection of resistin is unclear. This work was designed to examine the effect of mouse recombinant resistin on mRNA expression of Tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-10 (IL-10), Transforming growth factor-β1 (TGF- β1), and Heat shock protein-70 (HSP-70) in mouse model of stroke.Materials and Methods: Transient focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) in mice. TNF-α, IL-1β, IL-10, TGF-β1, and HSP-70 mRNA were detected at sham (0 hour), 3 hours, 6 hours, 12 hours, and 24 hours after MCAO using real-time QRT-PCR method. Moreover, animals were treated with resistin at the dose of 400ng/mouse at the commencement of MCAO, and mRNA expression of the cytokines and HSP-70 was measured 24 hours after MCAO.Results: Tumor necrosis factor-α and IL-1β mRNA expression markedly increased at 12-hour time point and then returned to the basal level at 24 hours after MCAO; but HSP-70 mRNA expression increased at 24-hour time point. Furthermore, resistin (400 ng/mouse) significantly increased TGF-β1 and IL-10 and decreased HSP-70 gene expression at 24 hours after MCAO.Conclusions: Our findings revealed that a molecular mechanism of attenuating ischemic damage by resistin administration probably is increased mRNA expression of anti-inflammatory cytokines. However, applying resistin in the clinical settings for the treatment of stroke deserves further researches in the future. [ABSTRACT FROM AUTHOR]

Growing evidences demonstrated that zinc oxide nanoparticles (ZnONPs) could reach the brain after oral ingestion; however, the “neurotoxicity of” ZnONPs after oral exposure has not been fully investigated. This study aimed to explore the “neurotoxicity of” ZnONPs (

Background: The aim of this study was to evaluate serum heat shock protein 70 (HSP70) and oxytocin levels, attachment and perceived social support levels in adolescents with parental bipolar disorder (BD) and Schizophrenia (SCZ)., Subjects and Methods: This study included 9 adolescents with SCZ parents, 30 adolescents with BD parents and 31 healthy adolescents. Brief Symptom Inventory (BSI), Relationship Scale Questionnaire-Adolescent Form (RSQ-A) and Multidimensional Scale of Perceived Social Support (MSPSS) were administered to all participants. In addition, serum HSP-70 and oxytocin levels were evaluated., Results: There was no significant difference between the groups in terms of attachment style, psychiatric symptoms and perceived social support. Serum HSP-70 levels were found to be lower in adolescents whose parents had BD. Serum oxytocin levels of the SCZ group were significantly lower than those of the BD group., Conclusions: HSP-70 level was found to be lower in adolescents with BD parents. Oxytocin level was found to be lower in adolescents with SCZ parents. These findings suggest that HSP-70 and oxytocin may be a marker of early life stress in adolescents with parental psychopathology. However, studies are needed to evaluate the relationship between attachment, oxytocin and HSP-70 in adolescents exposed to parental psychopathology in early life.

Background: Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis. Aim and Objectives: The aim of this study was to map the level of HSP-70 in vitiligo lesions to declare its role in the pathogenesis and activity of vitiligo. Materials and Methods: The study included thirty patients with vitiligo and 30 age- and sex-matched healthy controls. Vitiligo patients were divided as regards to the disease activity into highly active, moderately active, and inactive vitiligo groups. Skin biopsies were taken from the lesional and nonlesional skin of patients and from the normal skin of the controls. HSP-70 messenger RNA (mRNA) expression was estimated using quantitative real-time polymerase chain reaction. Results: Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease. Conclusions: HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease. [ABSTRACT FROM AUTHOR]

For locally advanced colorectal cancer (CRC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision or complete mesocolic excision is the standard therapeutic strategy, which is key to patient survival. Involvement of the tumor immune microenvironment is a factor that regulates tumor progression and sensitivity to nCRT in CRC. In this study, we aimed to identify the effect of heat-shock protein 70 (HSP70)/toll-like receptor-2 (TLR-2) on mFOLFOX sensitization for CRC. A total of 22 patients with advanced CRC who had received neoadjuvant mFOLFOX were enrolled and classified into the mFOLFOX-insensitive or -sensitive group, according to the tumor regression grade. The abundance of immune infiltrates was significantly higher in the post-operative pathological specimens of the mFOLFOX-insensitive group, as compared to those of the mFOLFOX-sensitive group. After transcriptome sequencing, differentially expressed genes between the two groups were annotated to inflammatory and immune responses using Gene Ontology (GO) analysis, and the TLR signaling pathway was analyzed using Kyoto Encyclopedia of Genes and Genomes pathway analysis. Significantly higher expression levels of HSP60, HSP70, HSP90, and TLR-2 in the mFOLFOX-insensitive group were detected using immunofluorescence assays. TIMER2.0 platform was introduced to further narrow the scope of HSP70 (HSPA6 or HSPA7) and TLR-2, which exhibited positive correlations with dendritic cells, Tregs, or CD4+ T cells and negative correlations with CD3+ or CD8+ T cells, implying that HSP70/TLR-2 activation mediates immunosuppressive cells to counteract CD8+ T cells, which may be a novel target of CRC treatment. A promising synergistic effect of mFOLFOX combined with a TLR-2 inhibitor was observed in vivo in mouse allograft models, which could be partly rescued by recombinant HSP70 protein. Immunohistochemical staining of allografts and immunofluorescence assays of clinical specimens corroborated the regulatory effects of the immune microenvironment. In summary, HSP70/TLR-2 activation can regulate the tumor immune microenvironment of CRC and further remodel its sensitivity to mFOLFOX. However, the specific mechanisms remain unclear and require further investigation. This study is expected to provide a new direction for the clinical treatment of CRC. [ABSTRACT FROM AUTHOR]

Context: Aegle marmelos L. Corr (Rutaceae) is an important Indian Ayurvedic medicinal plant used for the treatment of various ailments. However, little information is available on the anti-fatigue properties of its fruit. Objective: Evaluation of the physical endurance and exercise-induced oxidative stress modulating properties of A. marmelos fruit in mice. Material and methods: Radical scavenging activity of the fruit hydroalcoholic extract was evaluated using in vitro systems. The extract was further evaluated for its endurance-enhancing properties at three oral doses (100, 200 and 400 mg/kg b.wt) in BALB/c mice for 21 d using a swimming test. Results and discussion: The extract exhibited significant scavenging activity against DPPH (IC50, 351 ± 37 µg/ml) and ABTS radicals (IC50, 228 ± 25 µg/ml), respectively, with the polyphenol content of 95 µg/mg extract. It also inhibited AAPH radical-induced oxidation of biomolecules such as BSA protein (63%), plasmid DNA (81%) and lipids (80.5%). Administration of extract resulted in an increase in the duration of swimming time to exhaustion by 23.4 and 47.5% for medium and higher doses, respectively. The extract significantly normalized the fatigue-related biochemical parameters and also down-regulated the swim stress-induced over-expression of heat shock protein-70 and up-regulated the skeletal muscle metabolic regulators (GLUT-4 and AMPK1-α) by 2- and 3-fold, respectively, at the higher dose in muscle tissues. Conclusion: Our study demonstrates the anti-fatigue properties of A. marmelos fruit, most probably manifested by delaying the accumulation of serum lactic acid, increasing the fat utilization and up-regulating the skeletal muscle metabolic regulators. [ABSTRACT FROM AUTHOR]

Abstract: Acute kidney injury (AKI) is a common problem characterized by an inflammatory response in the kidney and oxidative stress. However, there are no interventions to prevent AKI. Glutamine is an important precursor of glutathione and has also been shown to induce heat shock proteins (HSP). Thus, glutamine may affect both oxidative stress and inflammation. This study was to explore the effects of glutamine pretreatment on nephrotoxic AKI and to investigate the underlying mechanisms. First, the effects of alternate doses of glutamine were compared in CD-1 mice with AKI induced with folic acid intra-peritoneal injection. Then the effects of glutamine quercetin (an HSP inhibitor), and quercetin+glutamine, were compared in the same AKI model. AKI were assessed with plasma creatinine, urine neutrophil gelatinase-associated lipocalin, and renal histology. Inflammatory response was monitored with renal tumor necrosis factor (TNF-α), chemkines (CXCL1 and CCL2) contents, and neutrophil infiltration. Oxidative injury was detected with reduced glutathione, malondialdehyde, and protein thiol. Glutamine provided dose-dependent renal protection. Pretreatment with quercetin, which was showed to inhibit HSP-70 expression, abolished glutamine's renal-protective effects. Quercetin also abrogated glutamine's beneficial effects on renal TNF-α, chemokines, and neutrophil infiltration. However, quercetin did not affect glutamine's anti-oxidative effects. These results suggest that glutamine's renal-protective effects are mainly related to its activation of HSP-70, which mitigates inflammatory response, renal neutrophil infiltration and subsequent AKI. Regulating neutrophil infiltration might be a potential therapeutic target for AKI. [Copyright &y& Elsevier]

Introduction The exact mechanisms of obesity-related kidney disease (ORKD) are not fully known. Heat shock proteins (HSPs) may play a role in ORKD mechanisms because of their role in cell apoptosis, cytoprotection, and inflammatory processes. We aimed to determine the role of circulating serum HSP-60 and HSP-70 levels as a biomarker for ORKD. Materials and methods This study included 40 ORKD patients, 40 obese age-matched and sex-matched controls with similar body mass index (BMI), and 40 healthy controls. Their serum biochemical and hemogram parameters as well as HSP-60 and HSP-70 levels were evaluated and compared. Their neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein levels were assessed to define inflammation.  Results The patients had significantly higher HSP-60 levels than the obese and healthy controls (537.58 ± 170.35, 430.80 ± 110.61, and 371.85 ± 76.34, respectively; p<0.00). The results revealed that the 24-hour urinary protein levels had a positive correlation (r= 0.544), whereas the glomerular filtration rate had a negative correlation (r = 0.38) with the serum HSP-60 level. According to the regression analysis performed on the HSP-60 and 24-hour urinary protein excretion levels, an increase in the HSP-60 level significantly increased the 24-hour urinary protein excretion rate (r=0.15; p<0.005). The HSP-60 levels were correlated with inflammatory markers Conclusion The serum HSP-60 levels increased in patients with ORKD. This increase was correlated with 24-hour urinary protein excretion. Increased circulating levels of HSP-60 may play a role in the initiation and/or progression of renal damage and inflammation. HSP-60 is a potential biomarker for ORKD. However, additional information and studies are required to further elucidate this finding., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Yıldırım et al.)

Abstract: The Babesia bigemina heat shock protein-70 gene (BbigHSP-70) was cloned from cDNA by polymerase chain reaction (PCR) and sequenced. The length of the gene is 1947bp and the predicted polypeptide is 649 amino acids long with a calculated molecular weight of 70.85kDa. BbigHSP-70 has a signal peptide of 15 amino acids. Phylogenetic analysis of the amino acid sequence of BbigHSP-70 showed that B. bigemina was most closely related to B. caballi and B. bovis and lies within a phylogenetic cluster with Theileria. rBbigHSP-70 was expressed in E. coli as a soluble GST-fusion protein with a molecular mass of 96.8-kDa. The serum raised in mice against rBbigHSP-70 detected the native protein in B. bigemina, B. bovis, B. caballi, B. gibsoni, and B. microti lysates and also reacted with B. bigemina, B. bovis, and B. caballi merozoites in the IFAT. Mice vaccinated with rBbigHSP-70 showed lower parasitemia against the challenge infection with B. microti than GST-vaccinated and non-vaccinated controls. These results added a new member of Babesia heat shock proteins70 that is well conserved among intraerythrocytic protozoa and demonstrated its protective effects in an experimental model of rodent babesiosis. [Copyright &y& Elsevier]

For analyzing the changes in immunoglobulins, HSP70, ghrelin levels in blood samples were collected from volunteers vaccinated against swine flu before the vaccinations and on days 3, and 15, and 1 and 2 months after the vaccination in the presence or absence of fever associated with the it. The study included 11 subjects having developed a fever, and 13 subjects not having a fever, and 20 control subjects. Immunoglobulins were measured by nephelometry, and HSP70 and ghrelins by appropriate ELISA tests. The level of ghrelin was reduced, while the level of HSP70 was significantly increased in subjects who developed fevers. When temperatures were normalized, both levels were found similar to the control group. These results indicate that the increase in serum immunoglobulins levels associated with vaccinations, along with, elevations in HSP70 and reduced ghrelin levels associated with fever, may be the important parameters in the clinical evaluation and follow-up of treatments with vaccines. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT)-generated cancer vaccines have shown promising results in preclinical studies and are being introduced in the clinics. Using an SCCVII mouse squamous cell carcinoma-based whole-cell autologous PDT vaccine model developed in our previous work, we have examined systemic effects in vaccinated mice that could be related to the induction of acute phase response. The upregulation of gene encoding serum amyloid P component (prototypic mouse acute phase reactant) was detected in the liver and to a lesser degree in the tumor of vaccinated mice at 24 h post-PDT vaccine treatment. A strong upregulation of gene for heat shock protein 70 was found in both the liver and tumor of mice at 4 h after their PDT vaccine treatment. Changes in the expression of genes for glucocorticoid-induced leucine zipper and serum- and glucocorticoid-regulated kinase 1 that are highly responsive to glucocorticoid modulation were uncovered in both the tumor and liver of vaccinated mice. A rise in the levels of serum corticosterone was detected in mice at 24 h after PDT vaccine treatment. The results indicate that a sudden appearance of a large number of PDT vaccine cells elicits host responses for securing their optimized clearance, which in addition to producing seminal acute phase reactants includes the engagement of glucocorticoid hormones. It is becoming increasingly clear that a consummate execution of this process of PDT vaccine cell removal is critical for tumor antigen recognition and the attainment of potent antitumor immune response. [ABSTRACT FROM AUTHOR]

Objectives: The neurobiological basis for autism remains poorly understood. However, research suggests that environmentalfactors and neuroinflammation, as well as genetic factors, are contributors. This study aims to test the role that might be played by heat shock protein (HSP)70, transforming growth factor (TGF)-β2, Caspase 7 and interferon-γ (IFN-γ)in the pathophysiology of autism. Materials and methods: HSP70, TGF-β2, Caspase 7 and INF-γ as biochemical parameters related to inflammation were determined in plasma of 20 Saudi autistic male patients and compared to 19 age- and gender-matched control samples. Results: The obtained data recorded that Saudi autistic patients have remarkably higher plasma HSP70, TGF-β2, Caspase 7 and INF-γ compared to age and gender-matched controls. INF-γ recorded the highest (67.8%) while TGF-β recorded the lowest increase (49.04%). Receiver Operating Characteristics (ROC) analysis together with predictiveness diagrams proved that the measured parameters recorded satisfactory levels of specificity and sensitivity and all could be used as predictive biomarkers. Conclusion: Alteration of the selected parameters confirm the role of neuroinflammation and apoptosis mechanisms in the etiology of autism together with the possibility of the use of HSP70, TGF-β2, Caspase 7 and INF-γ as predictive biomarkers that could be used to predict safety, efficacy of a specific suggested therapy or natural supplements, thereby providing guidance in selecting it for patients or tailoring its dose. [ABSTRACT FROM AUTHOR]

Background: The aim was to determine whether Bcl-2-associated athanogene-1 (Bag-1) and/or its binding protein heat shock protein-70 (Hsp70) exhibit deregulated expression in epidermal squamous cell carcinoma (SCC) and whether Bag-1 confers apoptosis resistance.Method: Immunohistochemistry for Bag-1 and Hsp70 was performed on 60 epidermal SCC and 10 normal skin samples. The epidermal SCC cell line SCC-13 was treated with 5-fluorouracil (5-FU) after Bag-1 knockdown to determine whether high Bag-1 levels contribute to growth and/or apoptosis resistance.Results: Normal epithelium expressed primarily nuclear Bag-1. Most tumours showed reduced nuclear Bag-1 staining, but a subset exhibited strong Bag-1 staining, with cytoplasmic Bag-1 staining intensity correlating with cytoplasmic Hsp70 staining intensity (r(s)=0.462; P<0.001) and less differentiation (P<0.001). Bag-1 knockdown resulted in markedly reduced SCC-13 cell yield, increased spontaneous apoptosis and enhanced sensitivity to 5-FU-induced apoptosis. Apoptosis induced by 5-FU in the Bag-1-knockdown cells was significantly greater than the additive apoptotic effect of 5-FU or Bag-1 knockdown alone.Conclusions: Overexpression of Bag-1 and Hsp70 in poorly differentiated SCC may confer both enhanced tumour cell growth and apoptosis resistance. Bag-1 may contribute to the resistance of more advanced epidermal SCC to chemotherapy. [ABSTRACT FROM AUTHOR]

The PO2 within the kidney changes dramatically from cortex to medulla. The present experiments examined the effect of changing PO2 on epithelial Na channel (ENaC)-mediated Na transport in the collecting duct using the mpkCCD-c14 cell line. Decreasing ambient O2 concentration from 20 to 8% decreased ENaC activity by 40%; increasing O2 content to 40% increased ENaC activity by 50%. The O2 effect required several hours to develop and was not mimicked by the acid pH that developed in monolayers incubated in low-O2 medium. Corticosteroids increased ENaC activity at each O2 concentration; there was no interaction. The pathways for O2 and steroid regulation of ENaC are different since O2 did not substantially affect Sgk1, α-ENaC, Gilz, or Usp2-45 mRNA levels, genes involved in steroid-mediated ENaC regulation. The regulation of ENaC activity by these levels of O2 appears not to be mediated by changes in hypoxia-inducible factor-1α or -2α activity or a change in AMP kinase activity. Changes in O2 concentration had minimal effect on α- or γ-ENaC mRNA and protein levels; there were moderate effects on β-ENaC levels. However, 40% O2 induced substantially greater total β- and γ-ENaC on the apical surface compared with 8% O2; both subunits demonstrated a greater increase in the mature forms. The α-ENaC subunit was difficult to detect on the apical surface, perhaps because our antibodies do not recognize the major mature form. These results identify a mechanism of ENaC regulation that may be important in different regions of the kidney and in responses to changes in dietary NaCl. [ABSTRACT FROM AUTHOR]

Infiltration of leukocytes into post-ischemic cerebrum is a well-described phenomenon in stroke injury. Because CD-8 T-lymphocytes secrete cytotoxic proteases, including granzyme-b (Gra-b) that exacerbates post-ischemic brain damage, we investigated roles of Gra-b in human stroke. To study the role of Gra-b in stroke, ischemic and non-ischemic tissues (from post-mortem stroke patients) were analyzed using immunoblotting, co-immunoprecipitation, terminal deoxy uridine nick end labeling (TUNEL) and Annexin-V immunostaining, and in vitro neuron survival assays. Activated CG-SH cells and supernatants were used to model leukocyte-dependent injury. Non-ischemic brain tissues were used as non-pathological controls. Non-activated CG-SH cells and supernatants were used as controls for in vitro experiments. Human stroke (ischemic) samples contained significantly higher levels of Gra-b and interferon-gamma inducible protein-10 (IP-10/CXCL10) than non-ischemic controls. In stroke, poly (ADP-ribose) polymerase-1 and heat shock protein-70 were cleaved to canonical proteolytic 'signature' fragments by Gra-b. Gra-b was also found to bind to Bid and caspase-3. Gra-b also co-localized with Annexin-V/TUNEL in degenerating neurons. Importantly, Gra-b inhibition protected both normal and ischemia-reperfused neurons against in vitro neurotoxicity mediated by activated CG-SH cells and supernatants. These results suggest that increased leukocyte infiltration and elevated Gra-b levels in the post-stroke brain can induce contact-dependent and independent post-ischemic neuronal death to aggravate stroke injury. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a common, potentially serious metabolic disorder. Over the long term, diabetes leads to serious consequences in a number of tissues, especially those that are insulin insensitive (retina, neurons, kidneys). It also causes a variety of functional and structural disorders in the central and peripheral nervous systems. We investigated whether neurodegenerative changes were observable in the hippocampus, cortex, and cerebellum after 4 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of melatonin. Male Wistar rats (n = 32) were divided into four groups (n = 8 each): untreated controls, melatonin-treated controls, untreated diabetics, and melatonin-treated diabetics. Experimental diabetes was induced by a single dose of STZ (60 mg/kg, intraperitoneal (ip)). For 3 days before the administration of STZ, melatonin (200 μg/kg/day, ip) was injected and continued for 4 weeks. Sections of hippocampus, cortex, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, brain tissues were examined immunohistochemically for the expression of glial and neuronal markers, including glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and heat shock protein-70 (HSP-70). No neurodegenerative changes were observed in the hippocampus, cortex, or cerebellum of the untreated diabetic group after 4 weeks compared with the other groups. We did not observe any change in GFAP, NSE, or HSP-70 immunostaining in the brain tissues of STZ-induced diabetic rats. In summary, after 4 weeks of STZ-induced diabetes in rats, no degenerative or immunohistochemical changes were detected in the hippocampus, cortex, or cerebellum. [ABSTRACT FROM AUTHOR]

Serological immunoscreening was used to identify a gene encoding heat shock protein-70 from Babesia gibsoni (BgHSP-70) that showed high homology with HSP-70s from other apicomplexan parasites. This gene corresponded to a full-length cDNA containing an open reading frame of 1968 bp predicted to result in a 70-kDa mature protein consisting of 656 amino acids. Analysis of the expression levels of BgHSP-70 indicated elevated transcription from cultured parasites incubated at 40°C for 1 h, but not at 30°C. Interestingly, antiserum raised against recombinant BgHSP-70 protein reacted specifically not only with a 70-kDa protein of B. gibsoni but also with a corresponding native protein of B. microti (BmHSP-70), indicating the high degree of conservation of this protein. The BmHSP-70 gene was then isolated and characterized and the immunoprotective properties of recombinant BgHSP-70 (rBgHSP-70) and rBmHSP-70 were compared in vitro and in vivo. Both proteins had potent mitogenic effects on murine and canine mononuclear cells as evidenced by high proliferative responses and IFN-γ production after stimulation. Immunization regimes in BALB/c and C57BL/6 mice using rBgHSP-70 and rBmHSP-70 elicited high antibody levels, with concurrent significant reductions in peripheral parasitaemias. Taken together, these results emphasize the potential of HSP-70s as a molecular adjuvant vaccine. [ABSTRACT FROM AUTHOR]

Abstract: Apoptosis Inducing Factor is a mitochondrial protein which upon translocation to nucleus causes large scale DNA fragmentation. The stimulus for the cytosolic release and nuclear translocation for this protein still remains to be understood. The role of calpains, cathepsin-b, Poly ADP (ribose) Polymerase and granzyme-b in the nuclear translocation of AIF has been investigated in the pathology of cerebral ischemia. Calpains, cathepsin-b and PARP-1 which were mostly confined to cytosol, lysosomes and nucleus respectively were found to be elevated in the mitochondrial fraction interacting with AIF in the western blot analysis and double immunofluorescence analysis. Western blot and immunohistochemical analysis revealed elevated levels of granzyme-b secreted by cytotoxic T lymphocytes and natural killer cells in the infarct of ischemic mouse brain. Co-immunoprecipitation revealed and western blot analysis the interaction and break down of Heat Shock Protein-70 an endogenous inhibitor of AIF into signature fragments by granzyme-b facilitating the nuclear translocation of AIF. Break down of HSP-70 correlated with the nuclear translocation of AIF observed in western and immunohistochemical analysis. These results indicate that multiple proteases were involved in the nuclear translocation of AIF during the pathology of cerebral ischemia. [Copyright &y& Elsevier]

Sudden sensorineural hearing loss (SSNHL) is frequently classified as ‘idiopathic’ since the causative factor responsible for its onset is not identified in most cases. In the present study, we determined whether SSNHL is clinically associated with serum anti-heat shock protein-70 (anti-HSP70) and antiphospholipids (anti-PLs) autoantibodies and whether these autoantibodies have an impact on the prognosis of SSNHL. Sera from 63 patients with SSNHL were screened prospectively for the presence of anti-HSP70 and anti-PLs autoantibodies by an enzyme-linked immunosorbent assay test. Anti-PLs antibodies in this study consisted of anticardiolipin, and anti-β2-glycoprotein-1 antibodies. Serum was assayed for anti-HSP70 IgG antibodies using recombinant human HSP70. Demographic, clinical, and audiometric variables were analyzed to find the possible role of serum autoantibodies in SSNHL patients. Sixteen patients (25.4%) had demonstrable anti-HSP70 antibodies in serum. Twenty-one patients (33.3%) showed a positive result for at least one isotype (IgM or IgG) of anti-PLs. In 19% of the patients, anti-HSP70 and anti-PLs antibodies were positive in two combinations. A statistically significant association was found between anti-HSP70 antibodies and the Siegel recovery grade subgroup. SSNHL patients who were positive for anti-HSP70 antibodies showed a significantly higher rate of complete recovery and incomplete but partial recovery than SSNHL patients without anti-HSP70 antibodies (p = 0.0496). Statistically significant association was found between total anticardiolipin, total anti-β2-glycoprotein-1, total anti-PLs, and anti-PLs in combination with anti-HSP70 antibodies and age (p = 0.0229). The detection of autoantibodies to HSP70 and PLs offers a pliable explanation for the immune-mediated mechanism of SSNHL. The present study confirms and supports previous studies regarding the association between anti-HSP70 and anti-PLs antibodies with SSNHL, and is the first to identify a positive association between anti-HSP70 antibodies and a positive outcome of SSNHL. Further studies are necessary in order to identify and further clarify the immunologic role of the presence of autoantibodies and their impact on the prognosis of SSNHL. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Unopposed PI3-kinase activity and 3′-phosphoinositide production in Jurkat T cells, due to a mutation in the PTEN tumour suppressor protein, results in deregulation of PH domain-containing proteins including the serine/threonine kinase PKB/Akt. In Jurkat cells, PKB/Akt is constitutively active and phosphorylated at the activation-loop residue (Thr308). 3′-phosphoinositide-dependent protein kinase-1 (PDK-1), an enzyme that also contains a PH domain, is thought to catalyse Thr308 phosphorylation of PKB/Akt in addition to other kinase families such as PKC isoforms. It is unknown however if the loss of PTEN in Jurkat cells also results in unregulated PDK-1 activity and whether such loss impacts on activation-loop phosphorylation of other putative PDK-1 substrates such as PKC. In this study we have addressed if loss of PTEN in Jurkat T cells affects PDK-1 catalytic activity and intracellular localisation. We demonstrate that reducing the level of 3′-phosphoinositides in Jurkat cells with pharmacological inhibitors of PI3-kinase or expression of PTEN does not affect PDK-1 activity, Ser241 phosphorylation or intracellular localisation. In support of this finding, we show that the levels of PKC activation-loop phosphorylation are unaffected by reductions in the levels of 3′-phosphoinositides. Instead, the dephosphorylation that occurs on PKB/Akt at Thr308 following reductions in 3′-phosphoinositides is dependent on PP2A-like phosphatase activity. Our finding that PDK-1 functions independently of 3′-phosphoinositides in T cells is also confirmed by studies in HuT-78 T cells, a PTEN-expressing cell line with undetectable levels of 3′-phosphoinositides. We conclude therefore that loss of PTEN expression in Jurkat T cells does not impact on the PDK-1/PKC pathway and that only a subset of kinases, such as PKB/Akt, are perturbed as a consequence PTEN loss. [Copyright &y& Elsevier]

Objective: The purpose of this study was to determine the relationship between preterm premature rupture of membranes, tumor necrosis factor-α, and heat shock protein-70 gene polymorphisms in multifetal gestations. Study design: Buccal swabs from 101 mother-neonate pairs of multifetal pregnancies were tested for single nucleotide polymorphisms at position -308 of the tumor necrosis factor-α gene and +1267 of the heat shock protein-70 gene. Pregnancy outcome data were obtained subsequently. Results: Tumor necrosis factor-α allele 2 carriage by the first-born occurred in 10 of 27 pregnancies (37.0%) that resulted in preterm premature rupture of membranes compared with 6 of 67 pregnancies (9.0%) without preterm premature rupture of membranes (P = .002). The allele frequency of tumor necrosis factor-α allele 2 and heat shock protein-70 allele 2 in the first born was higher in pregnancies that were complicated by preterm premature rupture of membranes (18.5% vs 4.5%; P = .003; and 57.7% vs 41.3%; P = .04, respectively). There was no relationship between tumor necrosis factor-α allele 2 or heat shock protein-70 allele 2 carriage by the second fetus or mother and preterm premature rupture of membranes. Conclusion: Tumor necrosis factor-α allele 2 and/or heat shock protein-70 allele 2 carriage by the first-born fetus is associated with preterm premature rupture of membranes in multifetal pregnancies. [ABSTRACT FROM AUTHOR]

In the present study, caspase-3 enzyme activity (apoptotic marker) and heat shock protein-70 (HSP70) expression in male rat liver after aflatoxin B1 (AFB1) treatment and the effect of melatonin (MEL) were investigated. Four groups of 20 rats each were used: controls, MEL-treated rats (MEL dose, 5 mg/kg body wt), AFB1-treated rats (50 μg/kg body wt) and MEL+AFB1-treated rats. After 8 weeks of daily treatment, biochemical assays in liver homogenates were done. The caspase-3 enzyme activity was measured using colorimetric method while the level of HSP70 expression was determined using dot blot analysis. In addition, the tissue levels of lipid peroxides (LPO), nitric oxide (NO), glutathione (GSH) and the enzyme activities of glutathione reductase (GR) and glutathione peroxidase (GSPx) were determined using colorimetric methods. The levels of caspase-3 activities and HSP70 level in AFB1 group were significantly higher than control group. Concomitantly, the levels of oxidative stress indices, LPO and NO, were significantly increased while the levels of antioxidants, GSH, GSPx and GR in AFB1 group were significantly decreased compared to their levels in controls. Caspase-3 activity was positively correlated with LPO while negatively correlated with GSH in rat livers treated with AFB1. The levels of caspase-3 activity, LPO, NO and HSP70 expression were significantly lower while the levels of GSH, GSPx and GR activities were significantly higher in MEL+AFB1 group than AFB1 group. In conclusion, higher levels of caspase-3 activity and HSP70 expression were associated with oxidative stress in rat liver treated with AFB1. The increased HSP70 expression in liver of AFB1 group may be due to a compensatory defense mechanism. MEL may effectively normalize the impaired antioxidants status, which consequently reduce both expression of HSP70 and apoptotic dysregulation in the liver. Thus, clinical application of MEL as therapy may benefit in cases of aflatoxicosis. [Copyright &y& Elsevier]

Objective To assess the validity of the Western blot immunoassay for heat shock protein-70 (hsp-70) for diagnosis of autoimmune inner ear disease. Study Design Retrospective study of 53 patients affected by sudden deafness (n = 19), idiopathic progressive sensorineural hearing loss (n = 24), and Meniere's disease (n = 10) who were treated from 1995 to 1999. The clinical course and response to corticosteroid were evaluated. Methods A purified hsp-70 antigen from bovine kidney cell line was used for the Western blot immunoassay. Results Only five patients (9.4%) showed anti-hsp-70 antibodies: Two presented a sudden sensorineural hearing loss (sudden deafness group), two showed an idiopathic progressive sensorineural hearing loss (idiopathic progressive sensorineural hearing loss group), and one was affected by fluctuating hearing loss (Meniere's disease group). A systemic autoimmune condition was observed in 29.1% of patients with idiopathic progressive sensorineural hearing loss. Conclusions The low sensitivity of Western blot immunoassay for patients affected by idiopathic progressive sensorineural hearing loss and Meniere's disease may result from either the long time elapsed from the hearing loss and vertigo to the initial examination or from the increased percentage of cases of systemic autoimmune disease present in patients with idiopathic progressive sensorineural hearing loss. More studies to detect the immune-mediated inner ear disease in Western blot immunoassay-negative patients are required. [ABSTRACT FROM AUTHOR]

The excessive blockade of dopamine D2 receptors (DRD2s) with long-term antipsychotic treatment is known to induce a dopamine supersensitivity state (DSS). The mechanism of DSS is speculated to be a compensatory up-regulation of DRD2s, but an excess blockade of DRD2s can also cause glutamatergic neuronal damage. Herein, we investigated whether antipsychotic-induced neuronal damage plays a role in the development of DSS. Haloperidol (HAL; 0.75 mg/kg/day for 14 days) or vehicle was administered to rats via an osmotic mini-pump. Haloperidol-treated rats were divided into groups of DSS rats and non-DSS rats based on their voluntary locomotion data. We then determined the tissue levels of glutamate transporter-1 (GLT-1)/glutamine synthetase (GS) and heat shock protein-70 (HSP-70) in the rats' brain regions. The levels of HSP-70 in the striatum and CA-3 region of the DSS rats were significantly higher than those of the control and non-DSS rats, whereas the dentate gyrus HSP-70 levels in both the DSS and non-DSS rats were increased versus the controls. The levels of GLT-1/GS in the CA-3 and nucleus accumbens were increased in the DSS rats. These results suggest that the DSS rats experienced striatal neuronal damage and indicate that a HAL-induced upregulation of HSP-70 and the GLT-1/GS system in the CA3 may be involved in the development of DSS. It remains unknown why the non-DSS rats did not suffer neuronal damage. In view of the need for therapeutic strategies for treatment-resistant schizophrenia, dopamine supersensitivity psychosis, and tardive dyskinesia, further investigations of our findings are warranted. • Dopamine supersensitivity state (DSS) rats, but not the non-DSS rats, experienced striatal neuronal damage. • Upregulation of the GLT-1/GS and HSP-70 in the hippocampal CA-3 might also be involved in the development of the DSS. • Chronic treatment with high doses of HAL may become largely destructive by causing neuronal damage in the dentate gyrus. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the possible role of heat shock protein-70 (HSP70) induction by 17-allylaminodemethoxygeldanamycin (17-AAG) in collagen-induced arthritis in rats., Material and Methods: Male Wistar rats were divided into five groups ( n  = 10/group) and were treated intraperitoneally twice a week for 4 weeks, namely normal control (saline), arthritis control (AR; saline), AR + 17-AAG, AR + methotrexate (MTX), and AR + 17-AAG + MTX. At the end of the treatments, arthritic score was determined and then the animals were sacrificed. Erythrocyte sedimentation rate (ESR), serum levels of HSP70, interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), rheumatic factor (RF), C-reactive protein (CRP), malondialdehyde (MDA), glutathione peroxidase (GPx), and matrix metalloproteinase-9 (MMP-9) were determined., Results: In the AR group, all parameters increased significantly, except for GPx, which showed a pronounced decrease. The 17-AAG and/or MTX treatments significantly reduced arthritic score, ESR, IL-17, TNF-α, RF, CRP, MDA, and MMP-9 with significant increase in GPx compared to the AR group. The HSP70 level was significantly higher in the AR + 17-AAG and the AR + 17-AAG + MTX groups but significantly lower in the AR + MTX group as compared to the AR group. Also, it was significantly lower in the AR + MTX group as compared to the AR + 17-AAG group., Conclusion: We concluded that HSP70 induction by 17-AAG attenuated the inflammatory process in a rheumatoid arthritis (RA) model induced by collagen, which suggested that HSP70 inducers can be promising agents in the treatment of RA.

Growing evidences demonstrated that zinc oxide nanoparticles (ZnONPs) could reach the brain after oral ingestion; however, the “neurotoxicity of” ZnONPs after oral exposure has not been fully investigated. This study aimed to explore the “neurotoxicity of” ZnONPs (<100 nm) after oral exposure to two doses; 40 and 100 mg/kg for 24 h and 7 days. The exposure to 40 and 100 mg/kg of ZnONPs for 24 h did not elicit “neurotoxicity” compared to normal control. However, the daily exposure to both doses for 7 days caused oxidative stress in brain tissue as detected by the elevation of the levels of malondialdehyde, the main product of lipid peroxidation and nitrite as an index of nitric oxide with concomitant decline in the concentrations of antioxidants. In addition, both doses resulted in DNA fragmentation which was confirmed by increased percentage of tailed DNA, DNA tail intensity and length and tail moment particularly with the dose 100 mg/kg. Moreover, both doses led to the elevation of the inflammatory cytokines along with increased apoptotic markers including caspase-3 and Fas. Heat shock protein-70 levels were also elevated possibly as a compensatory mechanism to counteract the ZnONPs-induced oxidative stress and apoptosis. The present results indicate the “neurotoxicity of” ZnONPs after recurrent oral exposure via oxidative stress, genotoxicity, inflammatory response and apoptosis. [ABSTRACT FROM AUTHOR]