Serum High Mobility Group Box 1 Levels Research Articles

Serum HMGB1 in febrile seizures

The role of high-mobility group box 1 (HMGB1) in the pathogenesis of febrile seizures (FSs) is unclear. In our controlled follow-up study, we compared serum levels of HMGB1 (s-HMGB1) in the same individuals after the first FS, during febrile episodes without a FS, after recurrent FS, during healthy periods after FS, and between patients and controls. In all, 122 patients with FSs were included in the final analysis, including 18 with recurrent FSs with a complete follow-up protocol. We recruited 30 febrile children and 18 matched febrile children without seizures as controls. S-HMGB1 was lower in patients with recurrent FSs after the first FS than that in matched febrile control children (median 1.12μg/L (0.14-2.95) vs 1.79μg/L (0.33-47.90), P<0.04). We did not find any other differences in s-HMGB1 between the groups. S-HMGB1 did not differ in different types of FSs. We updated a meta-analysis of s-HMGB1 in patients with FSs and found that the differences were significant only in the studies conducted in East Asian populations. We conclude that S-HMGB1 does not seem to be a key factor in the pathogenesis of FSs but differences in HMGB1 concentrations could explain some of the ethnicity related susceptibility to FSs.

High mobility box protein-1 may be a new biomarker in active interstitial lung disease of systemic sclerosis

&lt;b&gt;Introduction:&lt;/b&gt; To investigate the significance of high mobility group box 1 (HMGB1) levels as both an immune and inflammatory mediator in systemic sclerosis (SSC) patients with interstitial lung disease (SSC-ILD) and whether HMGB1 levels could be a biomarker for progression and disease activity.&lt;br /&gt; &lt;b&gt;Materials &amp;amp; methods:&lt;/b&gt; Our study included 27 patients diagnosed with SSC according to the 2013 ACR/EULAR classification criteria, along with 12 healthy controls (HC). Among the patients with a diagnosis of SSC, they were further categorized into two groups based on the presence of ILD with 19 patients having lung involvement and eight patients without. In ILD-positive group, the activity of the involvement was assessed using the simple Goh algorithm. Serum levels of HMGB1 were evaluated in all groups using ELISA method.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; Significantly higher serum HMGB1 levels were found in patients with SSC-ILD active disease when compared to those with inactive ILD involvement and HC (14.01 mg/dl vs. 7.87 mg/dl and 8.04 mg/dl).&lt;br /&gt; &lt;b&gt;Conclusions:&lt;/b&gt; Serum HMGB1 levels reflect the disease activity in SSC-ILD. HMGB1 could be used for a potential biomarker for detecting active lung disease.

Serum high mobility group box 1 as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes.

As a damage-associated molecular pattern protein, high mobility group box 1 (HMGB1) is associated with kidney and systemic inflammation. The predictive and therapeutic value of HMGB1 as a biomarker has been confirmed in various diseases. However, its value in diabetic kidney disease (DKD) remains unclear. Therefore, this study aimed to investigate the correlation between serum and urine HMGB1 levels and DKD progression. We recruited 196 patients with type 2 diabetes mellitus (T2DM), including 109 with DKD and 87 T2DM patients without DKD. Additionally, 60 healthy participants without T2DM were also recruited as controls. Serum and urine samples were collected for HMGB1 analysis. Simultaneously, tumor necrosis factor receptor superfamily member 1A (TNFR-1) in serum and kidney injury molecule (KIM-1) in urine samples were evaluated for comparison. Serum and urine HMGB1 levels were significantly higher in patients with DKD than in patients with T2DM and healthy controls. Additionally, serum HMGB1 levels significantly and positively correlated with serum TNFR-1 (R 2=0.567, p<0.001) and urine KIM-1 levels (R 2=0.440, p<0.001), and urine HMGB1 has a similar correlation. In the population with T2DM, the risk of DKD progression increased with an increase in serum HMGB1 levels. Multivariate logistic regression analysis showed that elevated serum HMGB1 level was an independent risk factor for renal function progression in patients with DKD, and regression analysis did not change in the model corrected for multiple variables. The restricted cubic spline depicted a nonlinear relationship between serum HMGB1 and renal function progression in patients with DKD (p-nonlinear=0.007, p<0.001), and this positive effect remained consistent across subgroups. Serum HMGB1 was significantly correlated with DKD and disease severity. When the HMGB1 level was ≥27 ng/ml, the risk of renal progression increased sharply, indicating that serum HMGB1 can be used as a potential biomarker for the diagnosis of DKD progression.

HMGB1 regulates Th17 cell differentiation and function in patients with psoriasis.

Psoriasis is an immune-mediated chronic inflammatory skin disease, in which T helper 17 (Th17) cells and its effective cytokine interleukin (IL)-17A play a pivotal pathogenic role. High mobility group box 1 (HMGB1) is an important proinflammatory cytokine, which has been confirmed to be highly expressed in the peripheral circulation and epidermis tissues of psoriasis patients. The regulatory effect of HMGB1 on IL-17A expression and function has been reported in some inflammatory and autoimmune diseases by theHMGB1-Toll-like receptor 4 (TLR4)-interleukin (IL)-23-IL-17A pathway. While, in the pathological environment of psoriasis, whether HMGB1 can exert the regulatory effect on IL-17A is not clear. We aimed to evaluate the role of HMGB1-TLR4-IL-23-IL-17A pathway in the pathogenesis of psoriasis and explore the possible regulatory mechanism of HMGB1 on Th17 cell differentiation. Serum levels of HMGB1, TLR4, IL-23, and IL-17A were quantified in 50 patients with moderate-to-severe plaque psoriasis and 30 healthy controls. Peripheral blood mononuclear cells were acquired from 10 severe psoriasis patients and administrated by different concentrations of recombinant-HMGB1 (rHMGB1) to detect the Th17 cell percentage, mRNA and protein levels of TLR4, IL-23, IL-17A and retinoid-related orphan receptor γt (RORγt). The serum levels of HMGB1, TLR4, IL-23, and IL-17A in psoriasis patients were significantly higher than healthy controls, especially in severe patients, and positively correlated with the severity index. There were also positive correlations between every two detected indicators of HMGB1, TLR4, IL-23, and IL-17A. In vitro study, rHMGB1 can promote the elevated expression of Th17 cell percentage as well as TLR4, IL-23, IL-17A, and RORγt in a dose-dependent manner. HMGB1 can contribute to the pathogenesis of psoriasis by regulating Th17 cell differentiation through HMGB1-TLR4-IL-23-RORγt pathway, then promotesIL-17A production and aggravates inflammation process. Targeting HMGB1 may be a possible potential candidate for the immunotherapy of psoriasis.

Correlation between neurofilament, HMGB1, MMP9, ds DNA blood levels and cognitive impairment in patients with neuropsychiatric systemic lupus erythematosus.

Diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is challenging due to nonspecific biomarkers. High serum levels of neurofilament protein light subunit (NFL), high mobility group box 1 (HMGB1), Matrix metalloproteinase-9 (MMP-9) and have been reported in several autoimmune diseases. The aim of this study was to examine whether their plasma levels could serve as a diagnostic or prognostic biomarker for NPSLE. There were 90 SLE patients enrolled in this cross-sectional study (87.8% women and 12.2% men with a mean age of 41.67±11.05 years). We assessed the mental status of patients, also we measured the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/ACR (SLICC/ ACR) Damage Index or SDI scores. Serum levels of NFL, HMGB1, MMP9, and ds-DNA were investigated to find a role in the pathophysiology of NPSLE. Among the 90 patients with SLE, 63 (70%) met the criteria of NPSLE syndrome. Our results have shown a notable difference concerning SEDIAC-2k score, SDI score, PANS, MoCA, and Beck anxiety depression, between the two groups (p < 0.05). Although serum level of all measured serum biomarkers (NFL, MMP-9, HMGB1, dsDNA) were higher in patients with NPSLE, the difference was not statistically significant. Interestingly, our results showed that the serum level of NFL was correlated with the serum level of HMGB-1 and MMP-9. (r: 0.411, P=0.003). Serum level of NFL, HMGB-1 and MMP-9 may be used to detect abnormal mental status in patients with SLE.

Structural changes in the retina and serum HMGB1 levels are associated with decreased cognitive function in patients with Parkinson's disease

BackgroundCognitive impairment is a serious nonmotor symptom in patients with Parkinson's disease (PD). Currently, there are few studies investigating the relationship of serum markers and retinal structural changes with cognitive function in PD. ObjectiveTo investigate the relationship between retinal structural changes, serum high mobility group box-1 (HMGB1) levels and cognitive function and motor symptoms in PD patients. MethodsEighty-nine participants, including 47 PD patients and 42 healthy subjects, were enrolled. PD patients were divided into Parkinson's disease with normal cognitive (PD-NC), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) groups. The motor and nonmotor symptoms of PD patients were evaluated with clinical scale. Serum HMGB1 levels were detected by enzyme-linked immunosorbent assay (ELISA), and ganglion cell-inner plexiform layer complex (GCIPL) thickness changes in the macula were quantitatively analyzed by swept source optical coherence tomography (SS-OCT) in all patients. ResultsCompared with the control group, the macular GCIPL (t = −2.308, P = 0.023) was thinner and serum HMGB1 (z = −2.285, P = 0.022) was increased in PD patients. Macular GCIPL thickness in patients with PD-MCI and PDD were significantly lower than that in PD-NC patients, but there were no significant difference between the PD-MCI and PDD groups. Serum HMGB1 levels in patients with PD-MCI and PDD were significantly higher than those in PD-NC patients, and serum HMGB1 levels in PDD patients were higher than those in PD-MCI patients. Correlation analysis showed that serum HMGB1 levels in PD patients were positively correlated with disease duration, HY stage, UPDRS-I score, UPDRS-III score, and UPDRS total score and negatively correlated with MOCA score. Macular GCIPL thickness was negatively correlated with HY stage and positively correlated with MOCA score, and macular GCIPL thickness was negatively correlated with serum HMGB1 level. Logistic regression analysis showed that elevated serum HMGB1 level, thinner macular GCIPL thickness, and higher HY stage were independent risk factors for Parkinson's disease with cognitive impairment (PD-CI). The areas under the receiver operating characteristic curve (AUC) for the serum HMGB1 level and macular GCIPL thickness-based diagnosis of PD-MCI, PDD and PD-CI based on in patients with PD were 0.786 and 0.825, 0.915 and 0.856, 0.852 and 0.841, respectively. The AUC for the diagnosis of PD-MCI, PDD and PD-CI with serum HMGB1 level and GCIPL thickness combined were 0.869, 0.967 and 0.916, respectively. ConclusionThe macular GCIPL thickness and serum HMGB1 level are potential markers of cognitive impairment in PD patients, and their combination can significantly improve the accuracy of the diagnosis of cognitive impairment in PD.

Effects of metformin therapy on HMGB1 levels in rheumatoid arthritis patients

ObjectiveThe traditional treatment of rheumatoid arthritis (RA) has some side effects. We aimed to explore the effect of metformin treatment on the expression of HMGB1, cytokines, T cell subtypes and the clinical outcomes in RA patients.MethodsThe present prospective cohort study recruited 124 RA patients (metformin group) who were treated with metformin and conventional therapy (methotrexate, hydroxychloroquine sulfate and sulfasalazine) and 98 RA patients (conventional therapy group) who were only treated with conventional therapy. All subjects were admitted from December 2018 to December 2021 and continuous medication for 90 days. The serum high mobility group box 1 (HMGB1), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometric were used to analyze the expression of CD4+ and CD8+. Demographic and clinical statistics including age, body mass index (BMI), sex, course of disease, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), visual analogue score (VAS)and disease activity score (DAS)-28 were collected.ResultsThe serum levels of HMGB1, CRP, IL-6, CD4+ expression and CD4+/CD8+ ratio were significantly increased in patients with DAS-28 score ≥ 2.6. The serum HMGB1 and cytokines levels of metformin group declined more quickly during the study time. Pearson’s analysis supported that a positive correlation existed between the HMGB1 and IL-6, TNF-α, CRP, CD4+, CD4+/CD8+ ratio, and VAS scores. HMGB1 could be a potential diagnostic biomarker for RA patients in active phase. Serum HMGB1 (95% CI 1.133–1.397, P < 0.001) was a factor associated with active RA.ConclusionThe serum HMGB1 levels were significantly increased in RA patients in active phase. The serum levels of HMGB1 and inflammatory factors and VAS scores were decreased gradually with metformin treatment. HMGB1 might act as a novel therapeutic target for RA.

Higher High-Mobility Group Box-1 Levels are Associated with White Matter Lesions in Ischemic Stroke Patients.

High-mobility group box-1 (HMGB1) is a useful biomarker for disease severity stratification and prognosis prediction. We aim to explore whether the circulating HMGB1 concentrations are associated with the white matter lesions (WMLs) burden in stroke patients. Between 2022 June and December 2022, patients with acute ischemic stroke were prospectively enrolled. HMGB1 levels were measured by an enzyme-linked immunosorbent assay after admission for all patients. The WMLs severity was assessed by the Fazekas scale. We dichotomized patients into those with moderate-severe WMLs (Fazekas score 3-6) versus those with none-mild WMLs (Fazekas score 0-2). Furthermore, based on the severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs), patients were categorized as none-mild (Fazekas score 0-1) or moderate-severe (Fazekas score 2-3). A total of 287 participants (mean age: 64.9 years; 157 male) were analyzed. The median serum HMGB1 levels were 7.3 ng/mL (interquartile, 4.3 ng/mL-12.3 ng/mL). After adjustment for potential confounders, elevated HMGB1 levels were associated with the presence of moderate-severe WMLs (first quartile vs fourth quartile, odds ratio [OR], 4.101; 95% confidence interval [CI], 1.948-8.633; P = 0.001) and moderate-severe PWMLs (first quartile vs fourth quartile, OR, 9.181; 95% CI, 4.078-20.671; P = 0.001). Similar results were found when the HMGB1 levels were analyzed as a continuous variable. This study demonstrated that increased HMGB1 levels were associated with the severity of WMLs, mainly in the periventricular region.

Serum HMGB1 is a biomarker for acute myocardial infarction with or without heart failure.

This study measured serum high mobility group box 1 (HMGB1) levels in patients with acute myocardial infarction (AMI) and/or heart failure (HF) and evaluated their relationship with peripheral inflammatory biomarkers and cardiac biomarkers, which have not been reported before. Of the patients, 55 had AMI without HF (AMI-HF ), 42 had AMI with HF (AMI+HF ), and 60 had HF without AMI (HF-AMI ) compared with 50 healthy controls. Blood samples were collected to assess serum HMGB1 levels and blood test-related inflammatory biomarkers (e.g., erythrocyte sedimentation rate [ESR], hs-CRP, uric acid, and white blood cell count) and cardiac biomarkers (e.g., MYO, cTnI, CKMB, CK, NT-proBNP, LDH, aspartate aminotransferase [AST], and alanine aminotransferase [ALT]). Compared to healthy controls, three groups of patients, especially those with AMI+HF , had significantly higher levels of serum HMGB1. All tested inflammatory biomarkers (except uric acid) were significantly positively correlated with HMGB1 in patients with AMI patients but not in patients with non-AMI. In addition, all tested cardiac biomarkers (except NT-proBNP in AMI-HF ) were significantly higher in patients with AMI than in control individuals. The levels of MYO, cTnI, CKMB, CK, AST, and ALT were not significantly changed in patients with HF-AMI compared to control individuals, but were still much lower than those in patients with AMI (except ALT). In all patients, the levels of NT-proBNP, and cTnI were significantly correlated with HMGB1 levels. Except for MYO, LDH, AST, and ALT, all cardiac biomarkers in AMI-HF and AMI+HF showed a significant correlation with HMGB1. Among risk factors, hypertension, diabetes, previous heart disease, and reduced left ventricular ejection fraction showed a significant correlation with HMGB1 in all disease groups.

Longitudinal monitoring of response to chemotherapy in patients with malignant pleural mesothelioma by biomarkers.

The aim of the study was to longitudinally investigate the serum levels of mesothelin, sestrin1, hyaluronan synthase 2 (HAS2), midkine, and high mobility group box 1 (HMGB1) before and after chemotherapy and at the time of relapse in malignant pleural mesothelioma (MPM) patients treated with chemotherapy and to compare the changes in biomarker levels with radiological treatment outcome. A total of 64 MPM patients treated with chemotherapy were enrolled in the study and longitudinally followed for changes in biomarker levels in response to treatment. Biomarkers evels were measured in serum using a human ELISA kit. Relative and absolute changes in biomarker levels were compared with the best radiological overall response at each time point. Median survival was 20.0 ± 2.4 (15.3-24.7) months in patients with partial and complete response, 17.0 ± 1.0 (15.0-19.0) months in patients with stable disease, and 9.0 ± 1.0 (7.0-11.0) months in patients with progressive disease. A significant decrease in serum levels of mesothelin, midkine, and HMGB1 was observed in patients with radiologically partial and complete responses to chemotherapy (p< 0.001, p= 0.016, and p= 0.039, respectively). In these patients, mesothelin levels decreased by 15%, midkine levels by 7%, and HMGB1 levels by 15%. In addition, HMGB1 serum levels were found to significantly increase by 15% in patients with radiologically progressive responses to chemotherapy compared to pretreatment serum levels (p= 0.035). In patients with partial and complete response to chemotherapy, mesothelin levels increased by 15%, midkine by 12%, and sestrin1 by 8% when the disease recurred (p= 0.004, p= 0.004 and p= 0.044, respectively). Biomarkers may be useful in the longitudinal monitoring of response to treatment in MPM. However, the results of our study should be validated in larger groups with sufficient case numbers from multicenter institutions.

Emodin improves glucose metabolism and ovarian function in PCOS mice via the HMGB1/TLR4/NF-ĸB molecular pathway.

Polycystic ovary syndrome (PCOS) is a reproductive disorder with an unclear etiology. It affects 5-10% of women worldwide and is largely associated with impaired glucose metabolism and obesity. High mobility group box 1 (HMGB1) is a nuclear protein associated with impaired glucose metabolism and PCOS. We sought to investigate the potential therapeutic effects of emodin on glucose metabolism and ovarian functions in PCOS mice via the HMGB1 molecular pathway. A high-fat diet (HFD) and dehydroepiandrosterone (DHEA) induced PCOS mouse model comprising four experimental groups was established: control, PCOS, PCOS plus emodin, and PCOS plus vehicle groups. Emodin administration attenuated obesity, elevated fasting glucose levels, impaired glucose tolerance, and insulin resistance, and improved the polycystic ovarian morphology of PCOS mice. Additionally, it lowered elevated serum HMGB1, LH, and testosterone levels in PCOS mice. Elevated ovarian protein and mRNA levels of HMGB1 and TLR4 in PCOS mice were also lowered following emodin treatment. Furthermore, emodin lowered high NF-ĸB/65 protein levels in the ovaries of PCOS mice. Immunohistochemical staining of the ovaries revealed strong HMGB1, TLR4, and AR expressions in PCOS mice, which were lowered by emodin treatment. Moreover, emodin significantly increased GLUT4, Irs2, and Insr levels that were PCOS. Overall, our study showed that emodin alleviated the impaired glucose metabolism and improved ovarian function in PCOS mice, possibly via the HMGB1/TLR4/NF-ĸB signaling pathway. Thus, emodin could be considered a potential therapeutic agent in the management of PCOS.

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission.

The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.

Association of circulating histone H3 and high mobility group box 1 levels with postoperative prognostic indicators in intensive care unit patients: a single-center observational study.

Damage associated molecular patterns (DAMPs) levels are associated with sepsis severity and prognosis. Histone and high mobility group box 1 (HMGB1) levels are also potential indicators of prognosis. We investigated the relationship between serum histone H3 and HMGB1 levels and the illness severity score and prognosis in postoperative patients. Postoperative serum histone H3 and HMGB1 levels in 39 intensive care unit (ICU) patients treated at our institution were measured. The correlation between peak histone H3 and HMGB1 levels in each patient and clinical data (age, sex, surgical time, length of ICU stay, and survival after ICU discharge), which also included the patients' illness severity score, was examined. Histone H3 but not HMGB1 levels were positively correlated with surgical time, the Sequential Organ Failure Assessment score, the Japanese Association for Acute Medicine acute phase disseminated intravascular coagulation diagnosis score, and the length of ICU stay. Both histone H3 and HMGB1 levels were negatively correlated with age. However, survival post-ICU discharge was not correlated with histone H3 or HMGB1 levels. Histone H3 levels are correlated with severity scores and the length of ICU stay. Serum histone H3 and HMGB1 levels are elevated postoperatively. These DAMPs, however, are not prognostic indicators in postoperative ICU patients.

Meta-analysis of HMGB1 levels in the cerebrospinal fluid and serum of patients with epilepsy.

Epilepsy pathogenesis and progression are strongly influenced by inflammation. High-mobility group box-1 (HMGB1) is a key proinflammatory factor. The purpose of this study was to quantify and assess the relationship between HMGB1 level and epilepsy. We searched Embase, Web of Science, PubMed, and the Cochrane Library for studies examining the relationship between HMGB1 and epilepsy. Two independent researchers extracted data and assessed quality using the Cochrane Collaboration tool. Data extracted were analyzed using Stata 15 and Review Manager 5.3. The study protocol was registered prospectively at INPLASY, ID: INPLASY2021120029. A total of 12 studies were eligible for inclusion. After exclusion of one study with reduced robustness, 11 studies were included, with a total of 443 patients and 333 matched controls. Two of the articles included cerebrospinal fluid and serum HMGB1 data, which were distinguished by "a" and "b," respectively. The meta-analysis indicated that in comparison with the control group, the HMGB1 level was higher in epilepsy patients (SMD = 0.56, 95% CI = 0.27-0.85, P = 0.0002). Subgroup analysis of specimen types indicated that both serum HMGB1 and cerebrospinal fluid HMGB1 were higher in epilepsy patients than in the control group, with the increase in cerebrospinal fluid HMGB1 being more obvious. Subgroup analysis of disease types demonstrated that the serum HMGB1 level of epileptic seizure patients (including febrile and nonfebrile seizures) was significantly higher than that of matched controls. However, serum HMGB1 levels did not differ significantly between mild epilepsy patients and severe epilepsy patients. Patient age subgroup analysis showed higher HMGB1 in adolescents with epilepsy. Begg's test did not indicate publication bias. This is the first meta-analysis to summarize the association between HMGB1 level and epilepsy. The results of this meta-analysis indicate that epilepsy patients have elevated HMGB1. Large-scale studies with a high level of evidence are needed to reveal the exact relationship between HMGB1 level and epilepsy.

Age- and Sex- Dependent Changes in Serum Levels of TAS, TOS, TLR2, TLR4, HSP60, HSP90, and HMGB1

Objective: Cellular and physiological functions may be affected in an age- and sex-specific manner. The aim of this study is to investigate sex- and age-specific differences in the serum levels of Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Toll-like Receptor 2 (TLR2), Toll-Like Receptor 4 (TLR4), Heat Shock Protein 60 (HSP60), Heat Shock Protein 90 (HSP90), and High Mobility Group Box 1 (HMGB1) as well as to examine the correlation between them. &#x0D; Methods: Four groups of mice, each including seven animals, were used in the present study: young males and females (6 months old); old males and females (24 months old). Blood samples were taken from the heart and serum was used to assay the levels of TLR2, TLR4, HSP60, HSP90, HMGB1, TAS and TOS. &#x0D; Results: HGMB1, TOS and OSI were higher in old females than in young females (p

The effects of etomidate on expression of high mobility group box 1 via the nuclear factor kappa B pathway in rat model of sepsis

ABSTRACT Etomidate is an anesthetic agent used in hemodynamically unstable patients, but its use has been controversial in septic patients. The response of high-mobility group box 1 (HMGB1), a late-phase lethal cytokine in sepsis, to etomidate has not been reported. This study investigated the effects of etomidate on the expression and release of HMGB1 and the underlying mechanism using a cecal ligation and puncture (CLP) model. Thirty-six male Sprague–Dawley rats were divided into sham, CLP, and Etomi groups. Sepsis was induced in the CLP and Etomi groups, and intravenous etomidate (4 mg/kg) was infused for 40 min immediately after operation in the Etomi group. Serum creatinine, alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and HMGB1 levels were measured 6 and 24 hours after surgery. Activation of nuclear factor (NF)-ĸB and HMGB1 mRNA expression in the liver, lung, kidney, and ileum tissues were measured, and immunohistochemical staining of HMGB1 was implemented. Increases of the TNF-α level 6 h after CLP and ALT and IL-6 levels 24 h after CLP were significantly inhibited by etomidate treatment. Etomidate treatment also significantly attenuated the increase in serum HMGB1 level at 6 and 24 h after CLP and suppressed the NF-ĸB and HMGB1 mRNA in multiple organs 24 h after CLP. Immunohistochemical staining also revealed that etomidate treatment inhibited HMGB1 expression. Etomidate inhibited the systemic release of HMGB1 and its expression in various organs. The mechanism may be associated with the inhibitory effects of etomidate on pro-inflammatory cytokine release and NF-ĸB activity.

Serum HMGB1 levels and its clinical significance in elderly patients with intertrochanteric fractures after intramedullary fixation surgery

Intramedullary fixation is a valuable alternative for the treatment of intertrochanteric fractures. However, further development of new biomarkers to predict the prognosis of the patient is still needed for timely and effective treatment and intervention. The present study aimed to explore the serum high-mobility group box 1 (HMGB1) levels in the prognosis of intertrochanteric fracture patients and its correlation with clinical results. The present prospective cohort study recruited 115 intertrochanteric fracture patients who were admitted from January 2015 to December 2019. All patients were evaluated preoperatively and treated (proximal femoral nail antirotation or intramedullary proximal femoral nail) by the same team. The serum HMGB1, interleukin-6, interleukin-1β, tumor necrosis factor α, and C-reactive protein levels were measured by enzyme-linked immunosorbent assay. Demographic and clinical data of all patients were collected. Harris score was used to assess the prognosis of intertrochanteric fracture patients after 6 months of treatment. Statistical analysis was conducted using SPSS software with P < .05 as statistically different. The time of the operation and the amount of bleeding in intramedullary proximal femoral nail were remarkably elevated compared with the proximal femoral nail antirotation group (P < .05). The age, proportion of complications and visual analogue score VAS after 72 hours of surgery in the Harris score < 80 group were remarkably increased compared with Harris score ≥ 80 group (P < .05). In addition, we found that the serum HMGB1 levels in Harris score < 80 group were markedly elevated than the patients in Harris score ≥ 80 group at all time points (P < .05). The results showed that the serum HMGB1 levels at postoperative 48 hours had the highest predictive value for predicting poor prognosis in intertrochanteric fracture patients. It was found that HMGB1, age and VAS after 72 hours of surgery were the risk factors for poor prognosis of intertrochanteric fracture patients. This study showed that the serum HMGB1 levels was significantly decreased in intertrochanteric fracture patients with bad prognoses. This study may provide a new approach to screening intertrochanteric fracture patients with worse prognoses in advance.

Correlation of HMGB1, TLR2 and TLR4 with left ventricular diastolic dysfunction in sepsis patients

Left ventricular diastolic dysfunction (LVDD) is a common consequence of sepsis due to dysregulated inflammatory responses. Here we aim to investigate high mobility group box 1 (HMGB1), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) as serum biomarkers to assess LVDD risk of patients with sepsis. We recruited 120 patients with sepsis, among which 52 had ultrasonically confirmed LVDD and 68 were without LVDD. Blood samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to analyse levels of HMGB1, TLR2 and TLR4 in serum. Multivariate analysis was performed to assess the odds ratio of the serum biomarkers. Spearman's correlation analysis was conducted to evaluate the correlation between the serum biomarkers to B-type natriuretic peptide (BNP) and cardiac troponin I (cTnl) levels and the ratios of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e′ ratios) in ultrasound. Receiver operating curve was used to measure the sensitivity and specificity of HMGB1, TLR2 and TLR4 individually and in combination as diagnostic markers. Elevated HMGB1, TLR2 and TLR4 had significant values in predicting LVDD suggested by high odds ratio (all P < .05). A significant correlation was found between these values and cTnl, the current gold standard for LVDD analysis. HMGB1, TLR2 and TLR4 also showed a high diagnostic sensitivity and specificity in ROC analysis. HMGB1, TLR2 and TLR4 are potentially valuable in predicting LVDD risk among patients with sepsis, providing additional tools with the capability of potentially assisting the clinical management of patients with sepsis.

Association between serum HMGB-1 (High Mobility Group Box-1) levels and clinical course in patients with COVID-19

Association between serum HMGB-1 (High Mobility Group Box-1) levels and clinical course in patients with COVID-19

Febrile Urinary Tract Infections in Children: The Role of High Mobility Group Box-1.

Differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN) is crucial for prompt clinical management. We investigated whether the high mobility group box-1 (HMGB1) could be a useful biomarker in differentiating between LUTI or APN. We enrolled seventy-four pediatric patients with suspected LUTI/APN, according to the positive or negative renal scintigraphy (DMSA) scan. If the first DMSA findings were abnormal, a second DMSA was performed after six months. Voiding cystourethrography ruled out vesicoureteral reflux (VUR). Higher serum (s) HMGB1 levels characterized the APN group when compared to LUTI patients (13.3 (11.8-14.3) versus 5.9 (5.2-6.8) ng/mL, p: 0.02), whereas there were no differences according to urine (u) HMGB1 values. sHMGB1 correlated with C-reactive protein (CRP) levels (β = 0.47; p: 0.02). Receiver operating characteristic curves identified the best diagnostic profile for detecting APN. sHMGB1 area under the curve was different from CRP (p: 0.01) and white blood cells (p: 0.003). After multivariate analyses, VUR (HR:4.81) and sHMGB1 (HR 1.16; p: 0.006) were independently associated with the risk of renal scarring development. sHMGB1 could represent a marker to differentiate APN from LUTI. Measurement of sHMGB1 could select children for early intervention or long-term follow-up.