Circulating heat shock protein 27 (HSPB1) levels in prediction of pre-eclampsia: A pilot study.

OBJECTIVE: To determine whether circulating heat shock proteins HSP27/HSPB1 and HSP90α/HSPC1 may be useful for early prediction of the occurrence of pre-eclampsia in asymptomatic women. METHODS: We have measured by ELISA the levels of HSPB1, HSPC1, and placental protein 13 (PP13) in serum samples from 44 women in the first trimester (10-12 weeks) and second trimester (17-20 weeks) of pregnancy. Western blot and immunohistochemistry for HSPB1 and HSPC1 were performed. RESULTS: HSPB1 serum levels were higher in women with pre-eclampsia than in normotensive pregnant women at the first and second trimester (P = 0.003), whereas PP13 levels decreased in women with pre-eclampsia only in the first trimester of gestation (P = 0.021). We also observed higher HSPB1 levels in patients with early-onset pre-eclampsia in the first and second trimester (P = 0.014). CONCLUSION: This pilot study points out that circulating HSPB1 levels in first and second trimester might be useful for predicting the occurrence of pre-eclampsia in asymptomatic women. Further validation studies are needed to finally establish this protein as a candidate predictive biomarker of pre-eclampsia.

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

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

Circulating chaperones in patients with aortic valve stenosis undergoing TAVR: impact of concomitant chronic kidney disease.

Chronic kidney disease (CKD) is a frequent comorbidity of aortic valve stenosis (AVS). Circulating chaperones have emerged as both effectors and prognostic markers for various diseases. We investigated the role of circulating chaperones in patients with severe AVS undergoing transcatheter aortic valve replacement (TAVR). In this observational cohort study, 159 consecutive patients undergoing TAVR were included and serum levels of Glucose-regulated protein 78 (GRP78) and heat shock protein 27 (HSP27) were measured by ELISA. The primary end point was defined as 1-year mortality. Patients with lower levels of circulating GRP78 (<1347 ng/mL) had an increased 1-year mortality rate compared to patients with higher levels of GRP78 (25.0% vs 10.3%, P = 0.026). GRP78 was associated with lower 1-year mortality in a univariate analysis (HR 0.354, P = 0.047). After adjusting for age, sex, several comorbidities and biomarkers, GRP78 (HR 0.295, P = 0.024) and CKD (HR 2.809, P = 0.044) remained independent predictors of the primary end point of 1-year mortality in a multivariate analysis. Patients with concomitant CKD had significantly higher levels of HSP27 compared to patients without CKD (1690 pg/mL vs 1076 pg/mL, P = 0.0109). In patients with CKD, elevated HSP27 was identified as a protective marker (1-year mortality: 9.6% vs 31.4%, log-rank P = 0.0166). Using cut-off values for GRP78 and HSP27 we were able to stratify patients with CKD undergoing TAVR into 4 groups with distinct mortality rates (50% vs 22.2% vs 24% vs 7.9%, log-rank P = 0.0170). GRP78 is an overall predictor of mortality after TAVR, while the combination of GRP78 and HSP27 helps to predict mortality in patients with CKD receiving TAVR.

Serum levels of anti-heat shock protein 27 antibodies in patients with chronic liver disease.

Heat shock protein 27 (HSP27), an intracellular molecular chaperone, is involved in the pathogenesis of cancer by promoting both tumor cell proliferation and resistance to therapy. HSP27 is also present in the circulation and circulating HSP27 (sHSP27) can elicit an autoimmune response with production of antibodies. Levels of sHSP27 are enhanced in patients with hepatocellular carcinoma (HCC); it is, however, unknown whether changes in HSP27 antibody levels occur in patients with HCC and can be exploited as a circulating biomarker of HCC. Our aim was to assess the potential association between newly diagnosed HCC and serum anti-HSP27 antibody levels. In this cross-sectional study, anti-HSP27 antibody levels were measured in serum samples from 71 HCC patients, 80 subjects with chronic liver disease, and 38 control subjects by immunoenzymatic assay. Anti-HSP27 antibody levels did not differ significantly among groups. However, in patients with chronic active hepatitis/cirrhosis, anti-HSP27 levels were significantly higher in subjects with a positive history of alcoholism (p = 0.03). Our data do not support the hypothesis that anti-HSP27 antibody levels may help identify patients with HCC among subjects with chronic liver disease. However, our finding that alcohol-related liver disease is associated with higher anti-HSP27 levels is novel and deserves further investigations.

Identification of BAG2 and Cathepsin D as Plasma Biomarkers for Parkinson's Disease.

The current diagnosis of Parkinson's disease (PD) mostly relies on clinical rating scales related to motor dysfunction. Given that clinical symptoms of PD appear after significant neuronal cell death in the brain, it is required to identify accessible, objective, and quantifiable biomarkers for early diagnosis of PD. In this study, a total of 20 patients with idiopathic PD and 20 age-matched patients with essential tremor according to the UK Brain Bank Criteria were consecutively enrolled to identify peripheral blood biomarkers for PD. Clinical data were obtained by clinical survey and assessment. Using albumin-depleted and immunoglobulin G-depleted plasma samples, we performed immunoblot analysis of seven autophagy-related proteins and compared the levels of proteins to those of the control group. We also analyzed the correlation between the levels of candidate proteins and clinical characteristics. Finally, we validated our biomarker models using receiver operating characteristic curve analysis. We found that the levels of BCL2-associated athanogene 2 (BAG2) and cathepsin D were significantly decreased in plasma of patients with PD (P = 0.009 and P = 0.0077, respectively). The level of BAG2 in patients with PD was significantly correlated with Cross-Culture Smell Identification Test score, which indicates olfactory dysfunction. We found that our biomarker model distinguishes PD with 87.5% diagnostic accuracy (area under the curve (AUC) = 0.875, P < 0.0001). Our result suggests BAG2 and cathepsin D as candidates for early-diagnosis plasma biomarkers for PD. We provide the possibility of plasma biomarkers related to the autophagy pathway, by which decreased levels of BAG2 and cathepsin D might lead to dysfunction of autophagy.

Synergistic effect of collagen and CXCL12 in the low doses on human platelet activation.

CXCL12, also known as stromal cell-derived factor-1, is a chemokine classified into CXC families, which exerts its function by binding to specific receptors called CXCR4 and CXCR7. Human platelets express CXCR4 and CXCR7 on the plasma membrane. It has been reported that CXCL12 potentiates to induce platelet aggregation in cooperation with agonists including collagen. However, the precise roles and mechanisms of CXCL12 in human platelet activation are not fully elucidated. In the present study, we investigated the effect of simultaneous stimulation with low doses of collagen and CXCL12 on the activation of human platelets. The simultaneous stimulation with collagen and CXCL12 induced the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble CD40 ligand (sCD40L) from human platelets in addition to their aggregation, despite the fact that the simultaneous stimulation with thrombin receptor-activating peptide (TRAP) or adenosine diphosphate (ADP), and CXCL12 had little effects on the platelet aggregation. The agonist of Glycoprotein (GP) Ⅵ convulxin and CXCL12 also induced platelet aggregation synergistically. The monoclonal antibody against CXCR4 but not CXCR7 suppressed the platelet aggregation induced by simultaneous stimulation with collagen and CXCL12. The phosphorylation of p38 mitogen-activated protein kinase (MAPK), but not p44/p42 MAPK, was induced by the simultaneous stimulation. In addition, the simultaneous stimulation with collagen and CXCL12 induced the phosphorylation of HSP27 and the subsequent release of phosphorylated-HSP27 from human platelets. SB203580, a specific inhibitor of p38 MAPK, attenuated the platelet aggregation, the phosphorylation of p38 MAPK and HSP27, the PDGF-AB secretion, the sCD40L release and the phosphorylated-HSP27 release induced by the simultaneous stimulation with collagen and CXCL12. These results strongly suggest that collagen and CXCL12 in low doses synergistically act to induce PDGF-AB secretion, sCD40L release and phosphorylated-HSP27 release from activated human platelets via p38 MAPK activation.

Evaluation of ABO blood group in subjects with CVD risk factors in a population sample from northeastern Iran.

BACKGROUND AND AIMS: The ABO blood group system is a genetic polymorphism which can affect the clearance of von Willebrand factor. We aimed to assess the levels of newer biomarkers of cardiovascular disease (CVD) risk; pro-oxidant-antioxidant balance (PAB), high sensitivity C-reactive protein (hs-CRP) and anti-heat-shock protein27 (anti-Hsp27) antibody titers in subjects with various blood groups (A, B, AB and O) and with or without traditional CVD risk factors. METHODS: The cross-sectional study comprised 6910 subjects. Antigen-antibody agglutination was evaluated by the slide test method for identification of ABO blood groups. RESULTS: Among three markers, only Serum anti-Hsp27 titers significantly differed between the four blood groups and showed the highest and lowest values in AB and O blood groups (0.26 ± 0.22 and 0.23 ± 0.18 OD, respectively; P < 0.05). Serum anti-Hsp27 was higher in individuals with an AB blood group with metabolic syndrome (MetS), dyslipidemia, hypertension (HTN) and obesity and it was lower in subjects with O blood group; though, two other biomarkers, serum PAB and hs-CRP, were not significantly different between the ABO blood groups. However, they were not different among blood groups in participants with or without diabetes mellitus (DM) (P > 0.05). CONCLUSION: Individuals with an AB blood group and high levels of anti-Hsp27 antibody titers may be predisposed to CVDs that can be mediated through the traditional CVD risk factors among middle-aged subjects from northeastern Iran. The fact that differences in anti Hsp27 are only found in the subgroup with other risk factors suggest that the difference between ABO blood groups is a consequence rather than a cause.

Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation.

Background: Staging of atrial fibrillation (AF) is essential to understanding disease progression and the accompanied increase in therapy failure. Blood-based heat shock protein (HSP) levels may enable staging of AF and the identification of patients with higher risk for AF recurrence after treatment. Objective: This study evaluates the relationship between serum HSP levels, presence of AF, AF stage and AF recurrence following electrocardioversion (ECV) or pulmonary vein isolation (PVI). Methods: To determine HSP27, HSP70, cardiovascular (cv)HSP and HSP60 levels, serum samples were collected from control patients without AF and patients with paroxysmal atrial fibrillation (PAF), persistent (PeAF) and longstanding persistent (LSPeAF) AF, presenting for ECV or PVI, prior to intervention and at 3-, 6- and 12-months post-PVI. Results: The study population (n = 297) consisted of 98 control and 199 AF patients admitted for ECV (n = 98) or PVI (n = 101). HSP27, HSP70, cvHSP and HSP60 serum levels did not differ between patients without or with PAF, PeAF or LSPeAF. Additionally, baseline HSP levels did not correlate with AF recurrence after ECV or PVI. However, in AF patients with AF recurrence, HSP27 levels were significantly elevated post-PVI relative to baseline, compared to patients without recurrence. Conclusions: No association was observed between baseline HSP levels and the presence of AF, AF stage or AF recurrence. However, HSP27 levels were increased in serum samples of patients with AF recurrence within one year after PVI, suggesting that HSP27 levels may predict recurrence of AF after ablative therapy.

Cortical Proteins Associated With Cognitive Resilience in Community-Dwelling Older Persons.

Importance: Identifying genes and proteins for cognitive resilience (ie, targets that may be associated with slowing or preventing cognitive decline regardless of the presence, number, or combination of common neuropathologic conditions) provides a complementary approach to developing novel therapeutics for the treatment and prevention of Alzheimer disease and related dementias. Objective: To identify proteins associated with cognitive resilience via a proteome-wide association study of the human dorsolateral prefrontal cortex. Design, Setting, and Participants: This study used data from 391 community-dwelling older persons who participated in the Religious Orders Study and the Rush Memory and Aging Project. The Religious Orders Study began enrollment January 1, 1994, and the Rush Memory and Aging Project began enrollment September 1, 1997, and data were collected and analyzed through October 23, 2019. Exposures: Participants had undergone annual detailed clinical examinations, postmortem evaluations, and tandem mass tag proteomics analyses. Main Outcomes and Measures: The outcome of cognitive resilience was defined as a longitudinal change in cognition over time after controlling for common age-related neuropathologic indices, including Alzheimer disease, Lewy bodies, transactive response DNA-binding protein 43, hippocampal sclerosis, infarcts, and vessel diseases. More than 8000 high abundance proteins were quantified from frozen dorsolateral prefrontal cortex tissue using tandem mass tag and liquid chromatography-mass spectrometry. Results: There were 391 participants (273 women); their mean (SD) age was 79.7 (6.7) years at baseline and 89.2 (6.5) years at death. Eight cortical proteins were identified in association with cognitive resilience: a higher level of NRN1 (estimate, 0.140; SE, 0.024; P = 7.35 × 10-9), ACTN4 (estimate, 0.321; SE, 0.065; P = 9.94 × 10-7), EPHX4 (estimate, 0.198; SE, 0.042; P = 2.13 × 10-6), RPH3A (estimate, 0.148; SE, 0.031; P = 2.58 × 10-6), SGTB (estimate, 0.211; SE, 0.045; P = 3.28 × 10-6), CPLX1 (estimate, 0.136; SE, 0.029; P = 4.06 × 10-6), and SH3GL1 (estimate, 0.179; SE, 0.039; P = 4.21 × 10-6) and a lower level of UBA1 (estimate, -0.366; SE, 0.076; P = 1.43 × 10-6) were associated with greater resilience. Conclusions and Relevance: These protein signals may represent novel targets for the maintenance of cognition in old age.

Cross talk between Hsp72, HMGB1 and RAGE/ERK1/2 signaling in the pathogenesis of bronchial asthma in obese patients.

BACKGROUND: The incidence of obesity-related asthma has shown a remarkable increase. OBJECTIVES: We aimed to explore the role of heat shock protein 72 (Hsp72) and receptor for advanced glycation end products (RAGE) axis with its downstream signaling in the pathogenesis of obesity-related asthma. METHODS: We enrolled a total of 55 subjects and divided them into three groups. Groups I and II included healthy, normal weight (n = 15) and obese (n = 15) subjects, respectively. Twenty-five obese asthmatics (group III) were subdivided into group IIIa (10 patients with mild to moderate asthma) and group IIIb (15 patients with severe asthma). High mobility group box 1 (HMGB1), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and urinary Hsp72 were immunoassayed. Hydrogen peroxide (H2O2) and free fatty acids (FFAs) levels were photometrically measured. RAGE mRNA expression was relatively quantified by real-time PCR. RESULTS: We found significant elevations of serum HMGB1, IL-8, MCP1, ERK1/2, FFAs, and H2O2 levels as well as urinary Hsp72 levels in obese subjects compared to healthy control. These were more evident in patients with severe asthma (group IIIb). Multivariate regression analysis identified Hsp72 and ERK1/2 as independent predictors of bronchial asthma severity. Receiver operating characteristic (ROC) curve analysis revealed that areas under the curve (AUC) for Hsp72 and ERK1/2 were 0.991 and 0.981, respectively, which denotes a strong predictive value for identifying the severity of bronchial asthma in obese patients. CONCLUSION: The current study highlights the role of Hsp72 and HMGB1/RAGE/ERK1/2 signaling cascade in the pathogenesis of bronchial asthma and its link to obesity, which could be reflected on monitoring, severity grading, and management of this disease.

Circulating heat shock protein 27 as a novel marker of subclinical atherosclerosis in type 2 diabetes: a cross-sectional community-based study.

BACKGROUND: Heat shock protein 27 (HSP27) has been proposed as a vital protective factor in atherosclerosis. The objective of the present study was to evaluate the association between circulating HSP27 and carotid intima-media thickness (IMT) in individuals with type 2 diabetes and to determine whether HSP27 represents an independent marker of subclinical atherosclerosis in this patient population. METHODS: We performed a cross-sectional community-based study in 186 Chinese subjects with a median duration of type 2 diabetes of 8.2 years who underwent ultrasound carotid IMT measurement. Serum HSP27 levels were assessed by ELISA. RESULTS: Serum HSP27 levels were significantly higher in the IMT (+, > 1.0 mm) group than in the IMT (-, ≤1.0 mm) group, with the median values of 8.80 ng/mL (5.62-12.25) and 6.93 ng/mL (4.23-9.60), respectively (P = 0.006). The discriminative value of HSP27 to evaluate IMT was 7.16 ng/mL and the area under the curve was 0.72 (95%CI = 0.64-0.80, P = 0.0065). Spearman's rank correlation analysis demonstrated that the concentrations of circulating HSP27 were positively associated with carotid IMT (r = 0.198, P = 0.007) and blood urea nitrogen (r = 0.170, P < 0.05). Furthermore, in the logistic model, serum HSP27 levels were found to be independent predictors for carotid IMT in type 2 diabetic patients after adjustment for onset age of diabetes, blood pressure, total cholesterol and C-reactive protein (OR = 1.085, P = 0.022). CONCLUSIONS: Circulating HSP27, positively correlates with carotid IMT, is an independent predictor for early atherosclerotic changes in diabetes, and may represent a novel marker of subclinical atherosclerosis in type 2 diabetes.

The effect of whole-body cryostimulation on body composition and leukocyte expression of HSPA1A, HSPB1, and CRP in obese men.

In recent years, the prevalence of obesity has increased dramatically and has become a 21st century epidemic. Obesity is associated with the development of many diseases, and therefore treatments that can reduce body mass are actively sought. The aim of this study was to examine the effect of 20 cryostimulation sessions on body composition in obese/high body mass (HBM, n = 12) males and normal body mass (NBM, n = 9) controls. The HBM group had a mean age = 29.08 ± 4.19 years, body fat percentage = 32.08 ± 6.16%, body mass index = 36.23 ± 8.13 kg/m2) and NBM group had a mean age = 22.00 ± 2.45 years, body fat percentage = 12.14 ± 4.93%, body mass index = 23.58 ± 2.00 kg/m2. Kilocalorie intake was similar for both groups. All participants received 20 sessions of systemic cryostimulation at -120°C for 2-3 min in a cryochamber. Blood samples were collected before the first session, 1 h after the 10th session, and 1 h after the 20th cryostimulation session. C-reactive protein (CRP) plasma concentrations, and expression of the heat shock protein genes (HSPA1A, HSPB1) and CRP mRNA in leukocytes were evaluated after 10 and 20 cryostimulation sessions. In both groups, 20 sessions were associated with a significant decrease in body mass, fat mass and the percentage of body fat. CRP concentrations were significantly higher in obese people before the first session and after 10 treatments, but not at the end of study. Expression of HSPA1A and HSPB1 mRNA gradually decreased with the number of cryostimulation sessions. A significant difference in HSPA1A expression was found after 20 sessions (NBM > HBM) and for HSPB1 at baseline and after 20 sessions (HBM > NBM). Our results show that cryostimulation influences body composition and that cryostimulation-induced HSP genes expression depends on the number of cryosessions and baseline body mass, and is differentially altered in HBM individuals. Further research on the interaction between body mass and cold adaptation is warranted.

Plasma immunoglobulin binding protein 1 as a predictor of development of lupus nephritis.

Objective: Urine levels of immunoglobulin binding protein 1 (IGBP1) are increased in patients with lupus nephritis (LN) compared with systemic lupus erythematosus (SLE) patients without nephritis. However, the clinical significance of IGBP1 level in plasma is unclear. We aimed to evaluate whether the plasma level of IGBP1 can predict future development of LN in SLE patients without nephritis. Methods: Forty-three SLE patients without nephritis were followed for 5 years. Plasma IGBP1 levels were measured using ELISA, and clinical and laboratory data were obtained at study entry. Development of LN was confirmed by renal biopsy. Cox regression analysis was performed to identify factors associated with development of LN, and receiver operating characteristic curve analysis was used to determine the predictive value of each factor. Results: Of the total 43 patients, eight (18.6%) developed LN during the follow-up period. Compared with patients who did not develop LN, those who developed LN had higher levels of plasma IGBP1 (6.3 ng/ml (range 4.3­9.6 ng/mL) vs. 13.3 ng/ml (range 7.2­31.3 ng/ml); p=0.023). In the Cox regression analysis, higher CRP (hazard ratio (HR)=1.325, 95% confidence interval (CI) 1.073­1.637, p=0.009), anti-dsDNA antibody (Ab; HR=1.066, 95% CI 1.012­1.124, p=0.017) and plasma IGBP1 (HR=1.091, 95% CI 1.034­1.152, p=0.002) were associated with future development of LN. Among these factors, anti-dsDNA Ab (area under the curve (AUC)=0.893) had the highest predictive value followed by plasma IGBP1 (AUC=0.761) and CRP (AUC=0.634). A combination of anti-dsDNA Ab and plasma IGBP1 as a composite predictor was highly specific (97%) for predicting the development of LN. Conclusions: Plasma IGBP1 can be used complementarily with anti-dsDNA Ab for detecting SLE patients at a higher risk of developing LN.

Validation and evaluation of a common biomarker in human cancers sera protein detected by a monoclonal antibody UNIVmAb.

OBJECTIVE: Management and diagnosis of multiple human cancers remains a challenge and search for a common biomarker is still debatable. In this manuscript we have evaluated the use of monoclonal antibody UNIVmAb, to detect the protein (H11) as a common biomarker for all cancers irrespective of the grade and origin. We have shown by both ELISA and Western Blot that the H11 protein, is a unique hyaluronan binding protein that has not been detected earlier. H11 protein was fractionated in an anion exchange column followed by cibacron blue gel exclusion chromatography. Hyaluronan binding H11 protein reacted with Monoclonal antibody UNIVmAb and b-HA inspite of b-Hyaluronan (biotinylated Hyaluronan) interaction and HA-Oligo (Hyaluronan oligosaccharides) competition from various grades of Human cancers sera. RESULTS: ELISA, Western blot and b-Hyaluronan interactions clearly showed an over-expression of UNIVmAb reacted H11 protein in all fifty cancer's sera when compared with seventy normal sera. UNIVmAb reactive H11 protein can be used as a common biomarker. We believe, UNIVmAb detected H11 protein, is a unique hyaluronan binding protein, that can be used as a common biomarker for all cancers.

Relationship Between Heat Shock Protein Expression and Obesity With and Without Metabolic Syndrome.

Background: Obesity is considered a chronic inflammatory disease in which the physiological mechanism responsible for reducing inflammation is weakened, prompting low-grade inflammation throughout the body. One of the key stress response systems that is dysregulated in obesity is the heat shock response, which is a critical defense mechanism that is activated in stressful conditions. Obesity is primary to metabolic syndrome (MetS) as it appears to lead to the increase in other MetS risk factors. Aim of the Study: We aimed to investigate the different expression levels of intracellular heat shock protein (iHSP) 70 and iHSP27 in obese patients with and without MetS and compare these levels to those of a lean control group. Patients and Methods: One hundred ten lean subjects were compared with 44 obese subjects without MetS and 56 obese subjects with MetS. HSP70 and HSP27 mRNA expression levels were measured by quantitative real-time polymerase chain reaction. Results: iHSP70 mRNA expression was significantly higher in obese subjects without MetS than in lean subjects (p = 0.04), whereas iHSP70 mRNA expression was significantly lower in obese subjects with MetS than in those without MetS (p = 0.02) as well as in those in the lean group (p = 0.03). iHSP27 mRNA expression was significantly lower in obese subjects with MetS than in those without MetS and in lean subjects (p = 0.037 and 0.031, respectively). Conclusion: We conclude that the intracellular expression levels of HSP70 and HSP27 may play an important role in the pathogenesis of MetS.

Clinical and cytokine profile of adult acute necrotizing encephalopathy.

BACKGROUND: Acute necrotizing encephalopathy (ANE), a fulminant encephalopathy, is often found in childhood. It is still uncertain whether adult patients with ANE display clinical features different from patients with typical pediatric onset. Furthermore, alterations in neuroinflammatory factors in patients with ANE have not been well-characterized. Here, we present an adult patient with ANE, and review all reported adult ANE cases in the literature. METHODS: Serum levels of five cytokines were checked in an adult patient with ANE and compared with gender/age-matched controls. Literature search was performed with PubMed, using the term as "acute necrotizing encephalopathy" with the filter of adult 19 + years. RESULTS: A total of 13 adult patients were reviewed. Compared with pediatric patients, adult ANE patients had similar clinical symptoms, biochemical data, and neuroimage findings, whereas adult ANE were more female-biased (female:male, 9:4) with a worse prognosis. Elevated cytokine levels in the serum and/or CSF is found in both adult-onset and pediatric-onset ANE. We found significantly elevated serum levels of IL-6 (17.17 pg/mL; healthy control: 1.43 ± 1.22 pg/mL) and VCAM-1 (3033.92 ng/mL; healthy control: 589.71 ± 133.13 ng/mL), and decreased serum TGF-ß1 level (14.78 ng/mL, healthy controls: 25.81 ± 6.97 ng/mL) in our patient. CONCLUSIONS: Our findings clearly delineate the clinical features and further indicate the potential change in cytokine levels in adult patients with ANE, advancing our understanding of this rare disease.

HSP27 expression in the human peripheral blood mononuclear cells as an early prognostic biomarker in coronary artery disease patients.

BACKGROUND: Coronary artery disease (CAD), is one of the leading causes of death globally. CAD risk factors, such as smoking, dyslipidemia, and obesity, are mainly associated with increased oxidative stress. Heat Shock Protein-27 (HSP27) has a protective role in conditions of oxidative stress. The aim of the current study was to investigate the relationship between HSP27 mRNA copy numbers in the peripheral blood mononuclear cell (PBMCs) and the degree of CAD progression. METHODS: A total of 103 subjects aged 49-71 years were recruited; Patients with CAD were categorized into two groups: patients having <50% stenosis (Angio-) and ≥50% stenosis (Angio+). The mRNA copy numbers of HSP-27 in PBMCs, anthropometric-parameters, fasting blood glucose (FBG), and the fasted serum lipid profile were evaluated. RESULTS: Angio+ patients had a significantly higher level of TC and LDL-C values compared with Angio- patients and the control group (p < 0.05). The HSP27 expression in PBMCs was significantly increased in Angio+ and Angio- subjects, compared to the control group. Moreover, there was a significant association between the FBG, TC, LDL-C and TG among the groups (p < 0.05). CONCLUSION: It was shown that the increased expression of HSP27 in PBMCs of CAD patients is significantly correlated with CAD severity in Angio+ subjects, which can be used as an early prognostic biomarker, indicating the degree of overall oxidative stress in patients. In order to verify this statement, it is suggested to measure Pro-oxidant- Antioxidant Balance (PAB) test by the same design in subsequent studies.

Serum levels of DNAJB9 are elevated in fibrillary glomerulonephritis patients.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease. Kidney biopsy is required to establish the diagnosis. Recent studies have identified abundant glomerular deposition of DNAJB9 as a unique histological marker of FGN. We developed an immunoprecipitation-based multiple reaction monitoring method to measure serum levels of DNAJB9. We detected a 4-fold higher abundance of serum DNAJB9 in FGN patients when compared to controls, including patients with other glomerular diseases. Serum DNAJB9 levels were also negatively associated with estimated glomerular filtration rate in patients with FGN. Serum DNAJB9 levels accurately predicted FGN with moderate sensitivity (67%) and with high specificity (98%) and positive and negative predictive value (89% and 95%, respectively). A receiver operating curve analysis demonstrated an AUC of 0.958. These results suggest that serum levels of DNAJB9 could be a valuable marker to predict FGN, with the potential to complement kidney biopsy for the diagnosis of FGN.

The level of the endoplasmic reticulum stress chaperone protein, binding immunoglobulin protein (BiP), decreases following successful tuberculosis treatment.

An increased Mycobacterium tuberculosis burden inside the host leads to higher demand of response proteins. This in turn results in metabolic shift and cellular stress, which is caused by the accumulation and trafficking of these proteins within the endoplasmic reticulum (ER). To resolve this, cells trigger the unfolded protein response (UPR), which is mainly mediated by binding immunoglobulin protein (BiP)/glucose-regulated protein 78 (GRP78) chaperone, and this in turn upregulates its transcription. This chaperone protein facilitates proper protein folding within the ER; however, it can also be passively secreted into the extracellular environment or be expressed on cell surfaces attached to anchor proteins and transmembrane proteins. This notion has been shown in studies on chronic inflammation, including cancer and arthritis, with the detection of BiP-specific antibodies from different sample types. The present study analysed secreted BiP from plasma samples collected from healthy participants and patients with newly diagnosed tuberculosis (TBdx), seen over the course of TB treatment at week 1 (W1), month 2 (M2), and month 6 (M6). The results revealed that during the initial TB disease and treatment period, cells are subjected to stress conditions resulting in metabolic shifts, which lead to the secretion of the intracellular UPR-mediating chaperone protein, BiP. This was indicated by mean differences between TBdx (mean 40.88ng/ml) and W1 (68.57ng/ml) in the TB participant groups. However, no difference was observed between the healthy group (mean 42.64ng/ml) and TBdx group (mean 40.88ng/ml). Analysis of paired time-point visits revealed increased BiP secretion during early TB treatment. The detection of BiP in plasma samples was found to decrease after successful TB treatment to levels comparable to those in the healthy controls. Evaluation of BiP levels in larger TB treatment studies may lead to the identification of a new target for early TB diagnosis and host-directed immunotherapy.

The Effects of Curcumin on Serum Heat Shock Protein 27 Antibody Titers in Patients with Metabolic Syndrome.

Metabolic syndrome (MetS) is associated with an increased risk of cardiovascular disease and diabetes mellitus. Inflammation and oxidant stress are features of MetS that can enhance the expression and release of heat shock proteins (Hsps), including the small heat shock protein, Hsp 27, and that may subsequently lead to the production of Hsp27 antibodies (anti-Hsp 27). Curcumin is an anti-inflammatory and antioxidant phytochemical that may ameliorate these features of MetS. We investigated the effects of unformulated curcumin and phospholipidated curcumin on antibody titers to heat shock protein 27 (anti-Hsp 27) in patients with MetS. A randomized double-blind, placebo-controlled clinical trial design was used in 120 patients with MetS (diagnosed according to the International Diabetes Federation [IDF] criteria). Participants were randomly allocated to 3 groups, with 40 individuals per group, that received either 1 g/d curcumin, phospholipidated curcumin, or a placebo for 6 weeks. The changes in serum concentrations of anti-Hsp 27 did not differ significantly between study groups (p = .283). There was no significant difference between baseline and end-of-trial concentrations of anti-Hsp 27 in groups supplemented with curcumin (p = .177), phospholipidated curcumin (p = .798), or placebo (p = .663). Curcumin supplementation (1 g/d) has no significant effects on anti-Hsp 27 titers in patients with MetS.