Serum High Mobility Group Box 1 Research Articles

Clinical and biochemical assessments of circulating High Mobility Group Box Protein1 in children with epilepsy: relation to cognitive function and drug responsiveness.

Childhood epilepsy is a major health concern posing a significant burden and having disastrous consequences for cognitive function. High Mobility Group Box1 (HMGB1) is an activator of neuroinflammation, and it is possibly involved in the initiation and progression of epilepsy. We aimed to investigate circulating HMGB1 in children with epilepsy and its connection to cognitive function and drug responsiveness. Case-control research included 100 epileptic youngsters and 100 healthy matched controls. Serum HMGB1 was measured using a commercially available ELISA assay. Cognitive functions were evaluated by the Stanford-Binet test 5th edition. Drug-resistant epilepsy (DRE) was found in 37% of the investigated patients. Epileptic children have lower cognitive function parameter levels versus the control group and lower cognitive function in the DRE group compared to the drug-responsive group (P-value < 0.0001). HMGB1 levels were significantly higher in the patients' group (6.279µg/L) compared to the control group (2.093µg/L) and in the drug-resistant group (14.26µg/L) versus the drug-responsive group (4.88µg/L). A significant negative correlation was detected between HMGB1 with Full-scale IQ (r = - 0.547, P = 0.000), Visual-spatial reasoning (r = - 0.501, P = 0.000), fluid reasoning (r = - 0.510, P = 0.000), and working memory (r = - 0.555, P = 0.000). Serum HMGB1 cut-off levels > 6.85µg/L differentiate drug-responsive from resistant patients. Elevated HMGB1 levels, especially in patients with drug-resistant epilepsy, correlate negatively with cognitive performance, emphasizing its importance as a potential marker for early prediction of drug resistance and impairment of cognitive function.

SCN1A rs6732655A/T polymorphism: Diagnostic and therapeutic insights for drug-resistant epilepsy.

A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs, resulting in heightened mortality rates, psychosocial challenges, and a diminished quality of life. Genetic factors, particularly within the SCN1A gene, and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases. In this extended study, we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response. To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response. The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases. We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique. The diagnostic performance of interleukin (IL)-1β, IL-6, and high mobility group box 1 (HMGB1) protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis. AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy. Serum biomarkers IL-6, IL1β and HMGB1 demonstrated diagnostic potential, with cutoff values of 4.63 pg/mL, 59.52 pg/mL and 7.99 ng/mL, respectively, offering valuable tools for epilepsy management. Moreover, specific genotypes (AA and AT) were found to be linked to the elevated levels of IL-1β and IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy. SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk. These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.

Elevated Serum HMGB1 Levels and Their Association with Recurrence of Acute Ischaemic Stroke.

The study aimed to investigate the correlation between baseline serum levels of high mobility group box 1 (HMGB1) and the recurrence of acute ischemic stroke (AIS). A total of 544 AIS patients were enrolled and followed up monthly. Serum HMGB1 levels were measured using enzyme-linked immunosorbent assay (ELISA). The primary endpoint was the first recurrence of AIS. During a median follow-up period of 43 months, 62 of the 544 AIS patients experienced a recurrence. Both HMGB1 levels and national institute of health stroke scale (NIHSS) scores were significantly higher in the recurrence group compared to the no-recurrence group (p<0.05). According to the receiver operating characteristic curve analysis, the combination (0.855, 95% CI: 0.800-0.911) of HMGB1 (0.745, 95% CI: 0.663-0.826) and NIHSS (0.822, 95% CI: 0.758-0.886) had a higher value for predicting AIS recurrence than either of them (p<0.05). Kaplan-Meier analyses demonstrated that the cumulative survival without AIS recurrence was significantly lower in patients in the high HMGB1 level group than in the low HMGB1 level group (p<0.05). The multifactorial Cox analyses indicated that elevated baseline serum HMGB1 levels (HR: 7.489, 95% CI:4.383-12.795) were a highly effective predictor of recurrence in AIS. Elevated baseline serum HMGB1 levels were found to be a highly effective predictor of recurrence in AIS.

Serum HMGB1 as a predictor for postoperative delirium in elderly patients undergoing total hip arthroplasty surgery.

Postoperative delirium (POD) is an acute mental disorder that occurs after surgery requiring general anesthesia. In animal studies, high-mobility group box 1 (HMGB1) plays a key role in mediating postoperative neuroinflammation and may have a direct impact on POD. The objective of this prospective observational study was to investigate the serum levels of HMGB1 in elderly POD patients undergoing total hip arthroplasty. This prospective observational study included 287 elderly patients who underwent total hip arthroplasty in our hospital from October 2019 to September 2022. Patients were assessed for the presence of POD using the Confusion Assessment Method (CAM) within 72 h of surgery. Serum HMGB1, interleukin (IL)-6, IL-1β, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) levels were measured using enzyme-linked immunosorbent assay (ELISA) before surgery, as well as at 24 h, 48 h and 72 h after surgery. Demographic and clinical data of all elderly patients were collected. The anesthesia time and surgical time in the POD group were significantly higher than those in the non-POD group. The serum levels of HMGB1, IL-6 and IL-1β in the POD group were significantly elevated compared to those in the non-POD group at all time points after surgery (p < 0.05). In addition, the serum levels of HMGB1 were positively correlated with TNF-α, IL-6 and IL-1β levels. HMGB1, IL-6 and IL-1β could be potential predictive biomarkers for the occurrence of POD in elderly patients undergoing total hip arthroplasty. Finally, we found that anesthesia time, surgical time, HMGB1, TNF-α, IL-6, and IL-1β were risk factors for POD in elderly patients undergoing total hip arthroplasty. Serum HMGB1 levels were markedly elevated in elderly POD patients undergoing total hip arthroplasty. In addition, HMGB1 could serve as a potential predictive biomarker for POD in elderly patients undergoing total hip arthroplasty.

Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B-NIT).

Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44+ effector memory T cells and CD69+ early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.

Diagnostic significance of serum levels of serum amyloid A, procalcitonin, and high-mobility group box 1 in identifying necrotising enterocolitis in newborns.

Necrotising enterocolitis (NEC) is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates. Serum amyloid A (SAA), procalcitonin (PCT), and high-mobility group box 1 (HMGB1) have emerged as potential biomarkers for NEC due to their roles in inflammatory response, tissue damage, and immune regulation. To evaluate the diagnostic value of SAA, PCT, and HMGB1 in the context of NEC in newborns. The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital. Clinical, radiological, and laboratory findings, including serum SAA, PCT, and HMGB1 Levels, were collected, and specific detection methods were used. The diagnostic value of the biomarkers was evaluated through statistical analysis, which was performed using chi-square test, t-test, correlation analysis, and receiver operating characteristic (ROC) analysis. The study demonstrated significantly elevated levels of serum SAA, PCT, and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls. The correlation analysis indicated strong positive correlations among serum SAA, PCT, and HMGB1 Levels and the presence of NEC. ROC analysis revealed promising sensitivity and specificity for serum SAA, PCT, and HMGB1 Levels as potential diagnostic markers. The combined model of the three biomarkers demonstrating an extremely high area under the curve (0.908). The diagnostic value of serum SAA, PCT, and HMGB1 Levels in NEC was highlighted. These biomarkers potentially improve the early detection, risk stratification, and clinical management of critical conditions. The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

Prognostic value of serum high-mobility group box 1 in neonates with neonatal encephalopathy.

This study aimed to investigate the diagnostic potential of serum high-mobility group box 1 (HMGB1) in neonatal encephalopathy (NE). A retrospective study was conducted, analyzing 216 neonates diagnosed with NE. The neonates were divided into two groups based on their outcomes at 28 days. Serum HMGB1 levels were compared between the two groups. ROC analysis was used to determine the predictive value of HMGB1. At 28 days, 174 infants had a good prognosis, while 42 had a poor prognosis. Infants with a poor prognosis had higher serum HMGB1 concentrations within 24 h of birth. Multifactorial analysis revealed that extremely preterm birth, extremely low birth weight, an Apgar score of 0-3 at 5 min, premature rupture of membranes by the mother, moderate to severe NE, and serum HMGB1 > 6.14 ng/mL are independent risk factors for poor prognosis. HMGB1 has predictive value for short-term prognosis with an area under the curve of 0.79. Elevated HMGB1 levels in the acute phase of NE are associated with poor short-term neonatal outcomes. The decrease in HMGB1 concentrations over time correlates with a good prognosis; whereas an increase suggests a poor prognosis. Early measurement of serum HMGB1 could aid in the prognostic assessment of neonates with NE. Although serum HMGB1 has emerged as a potential predictor of neonatal outcomes in neonatal encephalopathy, the relationship of HMGB1 levels to neonatal encephalopathy severity remains unclear. The current results demonstrate that infants with a poor prognosis had higher serum HMGB1 concentrations within 24 h of birth. Importantly, elevated serum HMGB1 levels in the acute phase of neonatal encephalopathy are associated with poor short-term neonatal outcomes. Our findings reveal the clinical values of HMGB1 in the prediction of neonatal outcomes in NE patients.

Associations of insulin sensitivity and immune inflammatory responses with child blood lead (Pb) and PM2.5 exposure at an e-waste recycling area during the COVID-19 lockdown.

Fine particular matter (PM2.5) and lead (Pb) exposure can induce insulin resistance, elevating the likelihood of diabetes onset. Nonetheless, the underlying mechanism remains ambiguous. Consequently, we assessed the association of PM2.5 and Pb exposure with insulin resistance and inflammation biomarkers in children. A total of 235 children aged 3-7years in a kindergarten in e-waste recycling areas were enrolled before and during the Corona Virus Disease 2019 (COVID-19) lockdown. Daily PM2.5 data was collected and used to calculate the individual PM2.5 daily exposure dose (DED-PM2.5). Concentrations of whole blood Pb, fasting blood glucose, serum insulin, and high mobility group box 1 (HMGB1) in serum were measured. Compared with that before COVID-19, the COVID-19 lockdown group had lower DED-PM2.5 and blood Pb, higher serum HMGB1, and lower blood glucose and homeostasis model assessment of insulin resistance (HOMA-IR) index. Decreased DED-PM2.5 and blood Pb levels were linked to decreased levels of fasting blood glucose and increased serum HMGB1 in all children. Increased serum HMGB1 levels were linked to reduced levels of blood glucose and HOMA-IR. Due to the implementation of COVID-19 prevention and control measures, e-waste dismantling activities and exposure levels of PM2.5 and Pb declined, which probably reduced the association of PM2.5 and Pb on insulin sensitivity and diabetes risk, but a high level of risk of chronic low-grade inflammation remained. Our findings add new evidence for the associations among PM2.5 and Pb exposure, systemic inflammation and insulin resistance, which could be a possible explanation for diabetes related to environmental exposure.

Increasing serum HMGB1 as a potential biomarker of treatment-resistant epilepsy in children: A case series and literature review

Epilepsy still causes the most burden compared to any other neurological diseases in children. Recent studies point to a connection between inflammation and epilepsy, particularly in epileptogenic epilepsy development, and the long-term effects of seizures. This pilot study describes the increasing serum High Mobility Group Box 1 (HMGB1) in two children with treatment-resistant epilepsy and how this marker could be considered a promising biomarker for treatment-resistant epilepsy in children. Case 1: A four-year-eight-month-old boy was presented with treatment-resistant epilepsy, communicating hydrocephalus on the ventriculoperitoneal shunt, cerebral palsy and global developmental delay. The seizure form was involuntary jerky head twisting and body shivering three times a day. Despite three antiepileptic medications (valproic acid, phenobarbital, and levetiracetam) given in maximal dose, the seizures were not well-controlled, three up to four times per week. The serum HMGB1 level was 5.93 ng/ml. Case 2: A four-year-three-month-old boy was presented with treatment-resistant epilepsy, cerebral palsy, global developmental delay, and sensorineural hearing loss. His first seizure started as status epilepticus. Symptoms progressed to generalized tonic seizures, with eyes bulging upward, occurring more than five times a day. The patient still suffers seizures daily for one minute despite the maximal dosage of valproic acid and levetiracetam therapy. The serum HMGB1 level was 5.342 ng/ml. Serum HMGB1 could be considered a potential biomarker for treatment-resistant epilepsy in children. Further diagnostic studies with adequate sample sizes are needed to support the proposed aetiology for developing targeted treatment options.

Dynamic changes and clinic significance of serum high mobility group box 1 in patients with total hip arthroplasty

Dynamic changes and clinic significance of serum high mobility group box 1 in patients with total hip arthroplasty

Insight into the Interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in IgA Vasculitis (IgAV).

The pathogenesis of IgAV, the most common systemic vasculitis in childhood, appears to be complex and requires further elucidation. We aimed to investigate the potential role of galactose-deficient immunoglobulin A1 (Gd-IgA1), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE) and protocadherin 1 (PCDH1) in the pathogenesis of IgAV. Our prospective study enrolled 86 patients with IgAV and 70 controls. HMGB1, RAGE, Gd-IgA1 and PCDH1 in serum and urine were determined by the enzyme-linked immunosorbent assay (ELISA) method at the onset of the disease and after a six-month interval in patients and once in the control group. Serum concentrations of HMGB1, RAGE and PCDH1 and urinary concentrations of HMGB1, RAGE, Gd-IgA1 and PCDH1 were significantly higher in patients with IgAV than in the control group (p < 0.001). Concentrations of HMGB1 (5573 pg/mL vs. 3477 pg/mL vs. 1088 pg/mL, p < 0.001) and RAGE (309 pg/mL vs. 302.4 pg/mL vs. 201.3 pg/mL, p = 0.012) in the serum of patients remained significantly elevated when the disease onset was compared with the six-month follow-up interval, and thus could be a potential marker of disease activity. Urinary concentration of HMGB1 measured in the follow-up period was higher in patients with nephritis compared to IgAV without nephritis (270.9 (146.7-542.7) ng/mmol vs. 133.2 (85.9-318.6) ng/mmol, p = 0.049) and significantly positively correlated with the urine albumine to creatinine ratio (τ = 0.184, p < 0.05), the number of erythrocytes in urine samples (τ = 0.193, p < 0.05) and with the outcome of nephritis (τ = 0.287, p < 0.05); therefore, HMGB1 could be a potential tool for monitoring patients with IgAV who develop nephritis. Taken together, our results imply a possible interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in the development of IgAV. The identification of sensitive biomarkers in IgAV may provide disease prevention and future therapeutics.

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.

High Mobility Group Box 1 Gene Polymorphism and Serum High Mobility Group Box 1, Interleukin 1 Beta, and Alpha-Klotho Crosstalk in Severe COVID-19 Patients

ABSTRACT Aim To evaluate the serum levels of HMGB1, IL1β, and α-klotho in COVID-19 patients with different disease severity, investigate their association with clinicopathological parameters, and to assess HMGB1 rs1045411 polymorphism and its relation with clinical severity. Methods 120 COVID-19 patients (89 critically ill, 15 severe, and 16 moderately severe) along with 80 healthy control were enrolled.The serum levels of HMGB1,IL1β, and α-klotho were determined by ELISA. The HMGB1 rs1045411 polymorphism was detected by RT- PCR. Results The serum levels of HMGB1, IL1β, and α-klotho were significantly higher in critically ill COVID-19 patients compared to other groups. The HMGB1rs1045411 polymorphism revealed a significant decrease in the percentage of T/T genotypes in COVID-19 patients compared to controls. The (ROC) analysis showed moderate diagnostic potential for serum HMGB1, IL1β, and α-klotho. Conclusion The serum HMGB1, IL1β, and α-klotho may be severity markers and promising therapeutic targets for COVID-19 patients.

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.

Serum High Mobility Group Box 1 Protein as an Early Marker of Pulmonary Arterial Hypertension in Neonates

Serum High Mobility Group Box 1 Protein as an Early Marker of Pulmonary Arterial Hypertension in Neonates

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.