High Mobility Group Protein B1 Research Articles

Atrazine induces phagocytotic dysfunction of microglia depends on nucleocytoplasmic translocation of acetylated HMGB1

Atrazine (ATR) is a widely applied herbicide which was named an environmental endocrine disrupting chemical (EDC). Increasing evidence indicates ATR causes neurotoxic effects resulting in central nervous system (CNS) disease. As the primary immunocytes in the CNS, microglia cells carry out their phagocytosis to maintain the CNS microenvironment by preventing damage from healthy cells. However, the mechanism in which ATR affects the phagocytic function of microglia remains unclear. The present study was designed to investigate the effect of ATR on the phagocytosis of microglia. BV-2 cells and primary microglia selected as microglial models in which BV-2 cells were administrated by ATR at different concentrations (0, 4, 8, 16 μM) for 24 h. Results demonstrated ATR dose-dependently increased the expression of ionized calcium binding adapter molecule 1 (Iba-1), indicating that microglia were activated. Microglial phagocytotic activity induced by ATR fluctuated at the different time points, accompanied by fluctuations in membrane receptor MERTK and cytoplasmic lysosomal marker LAMP1 (two markers related to cell phagocytosis). In this period, the expression of iNOS gradually increased. A mechanistic study further demonstrated that the translocation of High Mobility Group Protein-B1 (HMGB1) from nucleus to cytoplasm in the BV-2 and primary microglial cells induced by ATR, and the process showed a positive correlation with phagocytosis activity of BV-2 cells induced by ATR (r = 0.8030, P = 0.05; α = 0.1). ATR was also shown to spur the acetylation of HMGB1 by breaking the balance between acetylase P300 and deacetylase SIRT1. Unexpectedly, the inhibition of acetylating HMGB1 by resveratrol (Res) was effectively retained by HMGB1 in the nucleus, reversed the SIRT1 and MERTK expression, and enhanced the phagocytosis activity in BV-2 cells. Our results suggested that ATR exposure influenced microglial phagocytosis by acetylating HMGB1 further translocated it in the nucleoplasm.

CYTOR Promotes Proliferation of Lung Cancer Cell by Targeting miR-103a-3p to Upregulate HMGB1.

Lung cancer is one of the most dangerous malignant tumors to human health in the world. Previous researches have shown that cytoskeleton regulator RNA (CYTOR), a long noncoding RNA was involved in the occurrence and development of various types of cancer. The aim of this study is to investigate the clinical significance and biological function of CYTOR in lung cancer. Real-time quantitative PCR was applied to detect the expression of CYTOR. The proliferation of A549 and H1299 cells was analyzed by CCK8 assay. The luciferase reporter assay and RNA pull-down assay were used to reveal the interactions between CYTOR and its downstream targets. Western blot was used to detect the expression of high-mobility group protein B1 (HMGB1). Here we found CYTOR was upregulated in lung cancer tissues and cell lines. The proliferation of A549 and H1299 cells was inhibited after CYTOR silencing. In addition, CYTOR could directly interact with and negatively regulate miR-103a-3p, and miR-103a-3p inhibited cell proliferation by targeting HMGB1. The CYTOR/miR-103a-3p/HMGB1 axis promoted lung cancer cell proliferation. CYTOR sponges miR-103a-3p to promote the proliferation of lung cancer cells through HMGB1. The CYTOR/miR-103a-3p/HMGB1 axis plays a critical role in the progression of lung cancer.

A Focus on Intra-Abdominal Sepsis with Biomarkers: A Literature Review.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection according to the Third International Consensus Definitions for Sepsis and Septic Shock definitions. It is a clinical condition with high morbidity and mortality due to its complex pathophysiology and lack of a complete treatment. It constitutes a significant economic burden because it constitutes a substantial part of intensive care patients, and the treatment process is lengthy and costly. Therefore, early diagnosis and treatment of the disease are essential. After pneumonia, an essential source of sepsis is intra-abdominal infection. Due to the presence of multiple and polymicrobial sources of infection, abdominal sepsis progresses more seriously. The effective treatment of intra-abdominal infection consists of early recognition of the disease, control of the source, appropriate antibiotic therapy, and stabilization in the intensive care setting with an excellent surgical approach. We searched PubMed, EMBASE, MEDLINE, and the Cochrane Library. Two authors reviewed all identified abstracts and selected articles for full-text review. We included original studies assessing mediators in intraabdominal sepsis. Inflammatory and protein mediators such as acute phase protein and chemokine cytokines play an essential role in intra-abdominal sepsis. In clinical practice, white blood cell count, C-reactive protein, and procalcitonin are the most used parameters in the definition of abdominal infection. Tumor necrosis factor-alpha, interleukin-6, high-mobility group protein B1, and presepsin are other markers with high diagnostic efficiency, even though they are not used routinely. Despite everything, there is a need for highly effective markers that can be used in the diagnosis and follow-up of sepsis. Great hope is attached to these markers. This review aims to discuss the importance of the most used markers in the diagnosis and follow-up of abdominal sepsis and the markers on which there are essential studies in light of current literature.

Protein Markers of Diabetes Discovered in an African American Cohort.

Proteomics has been used to study type 2 diabetes, but the majority of available data are from White participants. Here, we extend prior work by analyzing a large cohort of self-identified African Americans in the Jackson Heart Study (n = 1,313). We found 325 proteins associated with incident diabetes after adjusting for age, sex, and sample batch (false discovery rate q < 0.05) measured using a single-stranded DNA aptamer affinity-based method on fasting plasma samples. A subset was independent of established markers of diabetes development pathways, such as adiposity, glycemia, and/or insulin resistance, suggesting potential novel biological processes associated with disease development. Thirty-six associations remained significant after additional adjustments for BMI, fasting plasma glucose, cholesterol levels, hypertension, statin use, and renal function. Twelve associations, including the top associations of complement factor H, formimidoyltransferase cyclodeaminase, serine/threonine-protein kinase 17B, and high-mobility group protein B1, were replicated in a meta-analysis of two self-identified White cohorts-the Framingham Heart Study and the Malmö Diet and Cancer Study-supporting the generalizability of these biomarkers. A selection of these diabetes-associated proteins also improved risk prediction. Thus, we uncovered both novel and broadly generalizable associations by studying a diverse population, providing a more complete understanding of the diabetes-associated proteome.

Biomarkers of Drug Resistance in Temporal Lobe Epilepsy in Adults.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in adults. Experimental and clinical data indicate that neuroinflammation and neurodegeneration accompanying epileptogenesis make a significant contribution to the chronicity of epilepsy and the development of drug resistance in TLE cases. Changes in plasma and serum concentrations of proteins associated with neuroinflammation and neurodegeneration can be predictive biomarkers of the course of the disease. This study used an enzyme-linked immunosorbent assay of the following plasma proteins: brain-derived neurotrophic factor (BDNF), tumor necrosis factor alpha (TNFa), and high-mobility group protein B1 (HMGB1) in patients with mesial TLE to search for biomarkers of the disease. The objective of the study was to examine biomarkers of the neuroinflammation and neurodegeneration of plasma: BDNF, TNFa, and HMGB1. The aim of the study was to identify changes in the concentration of circulating pro-inflammatory and neurotrophic factors that are prognostically significant for the development of drug resistance and the course of TLE. A decrease in the concentration of BDNF, TNFa, and HMGB1 was registered in the group of patients with TLE compared with the control group. A significant decrease in the concentration of HMGB1 in patients with drug-resistant TLE was observed. Aberrations in plasma concentrations of BDNF, TNFa, and HMGB1 in patients with TLE compared with the controls have been confirmed by earlier studies. A decrease in the expression of the three biomarkers may be the result of neurodegenerative processes caused by the long course of the disease. The results of the study may indicate the acceptability of using HMGB1 and TNFa as prognostic biological markers to indicate the severity of the disease course and the risk of developing drug resistance.

Hyperbaric Oxygen Therapy and Tissue Regeneration: A Literature Survey.

By addressing the mechanisms involved in transcription, signaling, stress reaction, apoptosis and cell-death, cellular structure and cell-to-cell contacts, adhesion, migration as well as inflammation; HBO upregulates processes involved in repair while mechanisms perpetuating tissue damage are downregulated. Many experimental and clinical studies, respectively, cover wound healing, regeneration of neural tissue, of bone and cartilage, muscle, and cardiac tissue as well as intestinal barrier function. Following acute injury or in chronic healing problems HBO modulates proteins or molecules involved in inflammation, apoptosis, cell growth, neuro- and angiogenesis, scaffolding, perfusion, vascularization, and stem-cell mobilization, initiating repair by a variety of mechanisms, some of them based on the modulation of micro-RNAs. HBO affects the oxidative stress response via nuclear factor erythroid 2-related factor 2 (Nrf2) or c-Jun N-terminal peptide and downregulates inflammation by the modulation of high-mobility group protein B1 (HMGB-1), toll-like receptor 4 and 2 (TLR-4, TLR-2), nuclear factor kappa-B (NFκB), hypoxia-inducible factor (HIF-1α) and nitric oxide (NO•). HBO enhances stem-cell homeostasis via Wnt glycoproteins and mammalian target of rapamycin (mTOR) and improves cell repair, growth, and differentiation via the two latter but also by modulation of extracellular-signal regulated kinases (ERK) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway. The HBO-induced downregulation of matrix metalloproteinases-2 and 9 (MMP-2/-9), rho-associated protein kinase (ROCK) and integrins improve healing by tissue remodeling. Interestingly, the action of HBO on single effector proteins or molecules may involve both up- or downregulation, respectively, depending on their initial level. This probably mirrors a generally stabilizing potential of HBO that tends to restore the physiological balance rather than enhancing or counteracting single mechanisms.

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca2+ accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.

Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy.

Multiple myeloma (MM) is an incurable hematological malignancy that lacks effective therapeutic interventions. Ferroptosis is a newly discovered form of cell death that has shown great potential for MM therapy. As a proteasome inhibitor and necroptosis inducer, shikonin (SHK) performs dual functions in MM cells. However, whether SHK inhibits the development of MM via ferroptosis or any other mechanism remains elusive. Here, we provide evidence that SHK treatment was capable of inducing ferroptosis and immunogenic cell death (ICD) in MM. The results showed that SHK treatment induced lactate dehydrogenase release, triggered cell death, evoked oxidative stress, and enhanced ferrous iron and lipid peroxidation levels. Furthermore, treatment with ferroptosis inhibitors reversed SHK-induced cell death, which indicated that ferroptosis contributed to this phenomenon. Meanwhile, ferroptosis was accompanied by the extracellular release of Adenosine 5'-triphosphate (ATP) and High mobility group protein B1 (HMGB1), which are characteristics of ICD. Further investigation showed that glutamic-oxaloacetic transaminase 1 (GOT1) acted as a critical mediator of SHK-induced ferroptosis by promoting ferritinophagy. In conclusion, our findings suggest that SHK exerts ferroptotic effects on MM by regulating GOT1-mediated ferritinophagy. Thus, SHK is a potential therapeutic agent for MM.

HMGB1 promotes the development of castration‑resistant prostate cancer by regulating androgen receptor activation.

AR signalling pathway reactivation plays a key role in the development of castration-resistant prostate cancer (CRPC). High-mobility group protein B1 (HMGB1) is an important factor involved in the occurrence and development of a variety of tumours by regulating gene transcription. In the present study, the association between HMGB1 and prostate cancer (PCa) and the effects of HMGB1 on androgen receptor (AR) transcription and signalling pathway reactivation in PCa cells in vitro and in vivo were evaluated. A bioinformatics method was used to determine the mRNA expression level of HMGB1 in PCa specimens and its correlation with the mRNA expression of AR. Immunohistochemical staining was used to detect the expression of these proteins in clinical PCa samples. Reporter gene and ChIP assays were performed to determine the activity of AR and the effect of HMGB1 on the ability of AR to bind to the promoters of prostate specific antigen and transmembrane protease, serine 2. A bioluminescence resonance energy transfer assay was employed to observe the direct interaction between HMGB1 and AR protein. Additionally, a castrated nude mouse xenograft tumour model was established to verify the effect of HMGB1 on PCa. The results revealed that HMGB1 expression was significantly increased in PCa specimens, which may have a strong correlation with AR expression. Moreover, HMGB1 could reactivate the AR signalling pathway, directly interact with AR, and promote the development of CRPC in an androgen-independent manner. The results of the present study indicated that HMGB1 promoted the development of CRPC by interacting with AR, which inferred that decreasing the expression of HMGB1 may be a potential effective method for CRPC prevention and treatment.

Mechanism of high mobility group protein B1 in lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome

To investigate the role and possible pathogenesis of high mobility group protein B1 (HMGB1) in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). (1) In vivo, 24 SPFC57BL/6 male mice were randomly divided into normal control group, ALI/ARDS model group, ethyl pyruvate (EP) treatment group and EP control group, with 6 mice in each group. The ALI/ARDS model was established by intraperitoneal injection of 20 mg/kg LPS. Mice in normal control group and EP control group were intraperitoneally injected with the same amount of sterile normal saline. Then, mice in the EP treatment group and EP control group were intraperitoneally injected with 40 mg/kg HMGB1 inhibitor EP. After 6 hours, the mice were sacrificed and lung tissues were collected. The expressions of heparan sulfate (HS), syndecans-1 (SDC-1), heparanase (HPA) and matrix metalloproteinases-9 (MMP-9) in lung tissues were detected by immunofluorescence technique. Orbital blood of mice was collected and serum was extracted to detect the content of HMGB1 by enzyme linked immunosorbent assay (ELISA). (2) In vitro, human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: normal control group, HUVECs damage group (treated with 1 mg/L LPS for 6 hours), HMGB1 group (treated with 1 μmol/L recombinant HMGB1 for 6 hours), HMGB1+EP group (treated with recombinant HMGB1 for 1 hour and then added 1 μmol/L EP for 6 hours), LPS+EP group (treated with LPS for 1 hour and then added 1 μmol/L EP for 6 hours), EP group (treated with 1 μmol/L EP for 6 hours). The expressions of HS, SDC-1, HPA and MMP-9 in endothelial cells were detected by immunofluorescence technique. (1) In vivo, light microscopy showed that the alveolar space was thickened after LPS stimulation, and there were a large number of inflammatory cells infiltrating in the alveolar space. Compared with ALI/ARDS model group, the expressions of HS and SDC-1 in lung tissue of EP treatment group were significantly increased [HS (fluorescence intensity): 0.80±0.20 vs. 0.53±0.02, SDC-1 (fluorescence intensity): 0.72±0.02 vs. 0.51±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly decreased [HPA (fluorescence intensity): 2.36±0.05 vs. 3.00±0.04, MMP-9 (fluorescence intensity): 2.55±0.13 vs. 3.26±0.05, both P < 0.05]; there were no significant changes of the above indexes in EP control group. Compared with ALI/ARDS model group, the content of serum HMGB1 in EP treatment group decreased significantly (μg/L: 131.88±16.67 vs. 341.13±22.47, P < 0.05); there was no significant change in the EP control group. (2) In vitro, compared with HMGB1 group, the expressions of HS and SDC-1 in HMGB1+EP group were significantly higher [HS (fluorescence intensity): 0.83±0.07 vs. 0.56±0.03, SDC-1 (fluorescence intensity): 0.80±0.01 vs. 0.61±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly lower [HPA (fluorescence intensity): 1.30±0.02 vs. 2.29±0.05, MMP-9 (fluorescence intensity): 1.55±0.04 vs. 2.50±0.06, both P < 0.05]; the expression of HS, SDC-1, HPA and MMP-9 had no significant changes in EP group. HMGB1 participates in LPS-induced injury of endothelial cell glycocalyx, leading to increased lung permeability, and inhibition of HMGB1 can alleviate lung injury.

LncRNA HOTAIR Inhibition by Regulating HMGB1/ROS/NF-κB Signal Pathway Promotes the Recovery of Spinal Cord Function

Spinal cord ischemia-reperfusion injury (SCII) is one of the most serious complications of clinical aortic aneurysm and vascular malformation surgery. Long noncoding RNA (lncRNA) is involved in the progression of SCII, whereas long noncoding RNA HOX transcript antisense RNA (lncRNA HOTAIR) is unclear in SCII. This study is aimed at confirming the role and related mechanism of HOTAIR in SCII. Later on, a model of SCII was established by clamping the aortic arch for 14 minutes. RNA expression of HOTAIR was detected via qRT-PCR at 12 h, 24 h, 36 h, and 48 h after SCII. The Tarlov scoring system and TUNEL assay were used to evaluate neurological function and neuronal apoptosis. Oxidative stress factor levels were assessed according to the instructions of the kit. Inflammatory cytokines were assessed by ELISA. Western blot was used to detect levels of p65, p-p65, I-κBα, and p-I-κBα. We found HOTAIR was raised in SCII rats. si-HOTAIR was able to reverse SCII-induced oxidative stress in SCII rats. The HMGB1 expression was upregulated in SCII tissues and negatively correlated with HOTAIR. HMGB1 was able to partially reverse si-HOTAIR inhibition of oxidative stress, inflammatory injury, and neuronal cell apoptosis in SCII. In addition, the ROS/NF-κB signaling pathway is involved in HOTAIR/HMGB1 regulation of SCII. In a word, HOTAIR inhibition is able to inhibit oxidative stress, inflammatory injury, and neuronal apoptosis in SCII through downregulation of the high mobility group protein B1(HMGB1), which is achieved by inhibiting the ROS/NF-κB signaling pathway. The HOTAIR/HMGB1/ROS/NF-κB molecular pathway may be a new mechanism for the treatment of SCII.

Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype owing to the lack of targeted therapeutic strategies. Immunogenic cell death (ICD), a modality of regulated cancer cell death, offered a novel option for TNBC via augmenting tumor immunogenic microenvironment. However, few ICD-inducing agents are currently available. Here, we showed that Trametes robiniophila Murr (Huaier) triggered ICD in TNBC cells by promoting cell surface calreticulin (CRT) exposure, and increasing release of adenosine triphosphate (ATP) and high-mobility group protein B1 (HMGB1). Co-culturing with Huaier-treated TNBC cells efficiently enhanced the maturation of dendritic cells (DCs), which was further validated via cell-based vaccination assay. In the xenograft mouse model, oral administration of Huaier led to tumor-infiltrating lymphocytes (TILs) accumulation and significantly delayed tumor growth. Besides, depletion of endogenous T cells obviously abrogated the effect. Mechanically, Huaier could elicit endoplasmic reticulum (ER) stress-associated ICD through eIF2α signaling pathway. Further studies revealed that circCLASP1 was involved in the Huaier-induced immunogenicity by binding with PKR in the cytoplasm and thus blocking its degradation. Taken together, we highlighted an essential role of circCLASP1/PKR/eIF2α axis in Huaier-induced ICD. The findings of our study carried significant translational potential that Huaier might serve as a promising option to achieve long-term tumor remission in patients with TNBC.

High Mobility Group Protein B1 Decreases Surface Localization of PD-1 to Augment T-cell Activation.

High-mobility group protein B1 (HMGB1) is a danger signaling molecule that has been found to trigger an effective antitumor immune response. However, the mechanisms underlying its antitumor effects are not fully understood. Here, we found that HMGB1 release induced by chemotherapy in patients with non-small cell lung cancer was negatively correlated with PD-1 expression on CD8+ T cells. In vitro analysis indicated that treatment with HMGB1 led to a significant decrease in the level of expression of PD-1 on CD8+ T cells. Further analysis demonstrated that HMGB1 reduced PD-1 expression by inducing dynamin-mediated internalization of the protein, leading to early endocytosis in the cytoplasm, and subsequently degradation in the lysosomes. In a xenograft model, HER2-targeted chimeric antigen receptor (CAR) T cells had enhanced function in the presence of HMGB1. These data identify a role for HMGB1 as a negative regulator of PD-1 signaling in lung cancer and the observed antitumor effect of HMGB1 on CAR T cells may provide a theoretical foundation for a new immunotherapy combination.

Grape-Seed-Derived Procyanidin Attenuates Chemotherapy-Induced Cognitive Impairment by Suppressing MMP-9 Activity and Related Blood-Brain-Barrier Damage.

(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been investigated. (2) Method: Adult male mice received 2.3 mg/kg cisplatin or saline injections for three cycles consisting of five daily injections followed by 5 days of rest. Procyanidin or saline was administered 1 h prior to cisplatin treatment. Cognitive testing, gelatin zymography, and blood–brain-barrier (BBB) penetration tests were performed after treatment cessation. RAW264.7 cells were treated by stimulated supernatant of SHSY5Y cells. In addition, high-mobility group protein B1 (HMGB1) expression and MMP-9 activity were tested. (3) Results: Repeated cisplatin treatment increased BBB penetration, MMP-9 activity, impaired performance in contextual fear conditioning, and novel object recognition tasks. The knockout of MMP-9 rescues cognitive impairment and cisplatin-induced upregulation of HMGB1 in SHSY5Y cells. HMGB1/TLR4/IP3K/AKT signaling contributes to the increased MMP-9 activity in RAW264.7 cells. Procyanidin treatment attenuates MMP-9 activity, BBB damage, and CICI. (4) Conclusions: The results indicated that MMP-9 activation and BBB disruption is involved in CICI. Procyanidin may effectively alleviate the harmful effects of cisplatin.

Serum expression of Vascular Endothelial-Cadherin, CD44, Human High mobility group B1, Kallikrein 6 proteins in different stages of laryngeal intraepithelial lesions and early glottis cancer.

BackgroundThe study was designed to evaluate the potential validity and utility of selected molecular markers in serum samples from patients with specific stages of laryngeal intraepithelial lesions that could serve as diagnostic tools in differentiation of benign and dysplastic lesions from invasive pathologies.MethodsProspective study included 80 consecutive patients with vocal fold lesions treated at the single otorhinolaryngology centre. All participants had surgical resection of the lesion. Blood samples were collected from each patient before the surgery. Final diagnosis was confirmed on histopathological examination and included 39 (48.75%) non-dysplastic lesions, eight (10%) low-grade dysplasia, six (7.5%) high-grade dysplasia and 27 (33.75%) invasive cancers. The ELISA procedures were performed according to the manufacturer’s instruction. Individual serum concentration of selected proteins was reported in ng/ml: Vascular Endothelial-Cadherin Complex (VE-cad), CD44, Human High mobility group protein B1(HMGB1), Kallikrein 6.ResultsThe highest mean levels of HMGB1, KLK6 and VE-cad were detected in sera of patients with low-grade dysplasia (81.14, 24.33, 14.17 respectively). Soluble CD44 was the most elevated in patients with non-dysplastic lesions (2.49). The HMGB1, KLK6 and VE-cad serum levels were increasing from non-dysplastic to low-grade dysplasia and followed by the decrease for high-grade dysplasia and invasive cancer, however the differences were not significant (p-values 0.897, 0.354, 0.1 respectively). Patients’ serum had the highest CD44 concentration in non-dysplastic and low-grade dysplasia with the following decrease through high-grade dysplasia and invasive cancer. GERD symptomatic patients had higher levels of KLK6 and CD44 than other patients (p-value 0.06 and 0.084 respectively). There were no significant differences of biomarkers levels related to patients’ gender (p-value from 0.243 to 1) or smoking status (p-value from 0.22 to 0.706).ConclusionsVE-cad, HMGB1, CD44 and KLK6 did not prove to be reliable biomarkers implicating malignant potential within vocal fold hypertrophic intraepithelial lesions.

The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma

To evaluate the value of high mobility group protein B1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the diagnosis, efficacy monitoring and prognosis of newly diagnosed multiple myeloma (MM) patients. Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sRAGE levels of the patients. ROC was used to further analyze the efficacy of serum HMGB1 and sRAGE levels on the diagnosis of MM. At the same time, the serum levels of HMGB1 and sRAGE before and after chemotherapy were compared, and their values in the evaluation of curative effect of MM patients were analyzed. According to the mean values of serum HMGB1 and sRAGE, all the patients were divided into different groups, the clinical characteristics and survival status of the patients were compared. Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group, while sRAGE level was lower (t=11.363,6.127, P<0.001). The AUC of serum HMGB1 and sRAGE in the MM patients was 0.955 and 0.811, respectively. After 3 courses of chemotherapy, HMGB1 level of the patients in CR group was lower than before chemotherapy, while in PD group was higher, as well as sRAGE level of the patients in PR group (P<0.05). There were significant differences in R-ISS stage, HGB, CRP, ESR, CD56, CD117, D13S319 deletion between HMGB1 high expression group and HMGB1 low expression group (χ2=3.920, 6.522, 6.65, 4.16, 3.945, 6.65, 4.16, P<0.05), while there were significant differences in ISS stage, CRP and CD56 between sRAGE low expression group (28 cases) and sRAGE high expression group (22 cases) (χ2=4.565, 4.711, 5.547, P<0.05). Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition, for PFS Tlow>Thigh (χ2=9.470, P<0.05), and for OS Tlow>Thigh (χ2=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS Tlow<Thigh (χ2=1.661, P>0.05), and for OS Tlow<Thigh (χ2=2.048, P>0.05). Cox analysis showed that LDH and HMGB1 were the factors affecting the prognosis of the patients, and both of them affected PFS (HR=2.771, 95% CI: 1.002-7.662, P=0.049; HR=6.022, 95% CI: 1.689-21.470, P=0.006), while HMGB1 also affected OS (HR=4.275, 95% CI: 1.183-15.451, P=0.027). The serum HMGB1 and sRAGE have certain auxiliary value for the diagnosis and curative effect monitoring of newly diagnosed MM patients, and serum HMGB1 is expected to be an auxiliary detection index for the prognosis of MM.

COVID-19 Vaccination Limits Systemic Danger Signals in SARS-CoV-2 Infected Patients.

Vaccination with an mRNA COVID-19 vaccine determines not only a consistent reduction in the risk of SARS-CoV-2 infection but also contributes to disease attenuation in infected people. Of note, hyperinflammation and damage-associated molecular patterns (DAMPs) have been clearly associated with severe illness and poor prognosis in COVID-19 patients. In this report, we revealed a significant reduction in the levels of IL-1ß and DAMPs molecules, as S100A8 and High Mobility Group Protein B1 (HMGB1), in vaccinated patients as compared to non-vaccinated ones. COVID-19 vaccination indeed prevents severe clinical manifestations in patients and limits the release of systemic danger signals in SARS-CoV-2 infected people.

Sodium Tanshinone IIA Sulfonate Improves Adverse Ventricular Remodeling Post-MI by Reducing Myocardial Necrosis, Modulating Inflammation, and Promoting Angiogenesis.

Myocardial infarction (MI) leads to pathological cardiac remodeling and heart failure. Sodium tanshinone IIA sulfonate (STS) shows to possess therapeutic potential. The present study aimed to explore the potential role of STS in ventricular remodeling post-MI. Mice were randomly divided into sham, MI + normal saline (NS) and MI + STS (20.8 mg/kg/day intraperitoneally) groups. MI was established following left anterior descending artery ligation. Cardiac function was evaluated using echocardiography. Scar size and myocardial fibrosis-associated markers were detected using Masson's trichrome staining and western blot analysis (WB). Necrosis and inflammation were assessed using H&E staining, lactate dehydrogenase (LDH) detection, ELISA, immunohistochemical staining, and WB. Furthermore, angiogenesis markers and associated proteins were detected using immunohistochemical staining and WB. Mice treated with STS exhibited significant improvements in cardiac function, smaller scar size, and low expression levels of α-smooth muscle actin and collagen I and III at 28 days following surgery, compared with the NS-treated group. Moreover, treatment with STS reduced eosinophil necrosis, the infiltration of inflammatory cells, plasma levels of LDH, high mobility group protein B1, interleukin-1β and tumor necrosis factor- α, and protein expression of these cytokines at 3 days. Macrophage infiltration was also decreased in the STS group in the early phase. Additionally, CD31+ vascular density, protein levels of hypoxia-inducible factor- 1α, and vascular endothelial growth factor were elevated in the STS-treated mice at 28 days. STS improved pathological remodeling post-MI, and the associated therapeutic effects may be a result of a decrease in myocardial necrosis, modulation of inflammation, and an increase in angiogenesis.

Silencing high mobility group protein B1 inhibits malignant biological behavior of glioblastoma cells

Silencing high mobility group protein B1 inhibits malignant biological behavior of glioblastoma cells

Two New Alkali/Cadmium Bimetallic Coordination Polymers: Luminescent Properties and Cancer Prevention by Regulating the Interaction Between High Mobility Group Protein B1 and Immune Cells

Two New Alkali/Cadmium Bimetallic Coordination Polymers: Luminescent Properties and Cancer Prevention by Regulating the Interaction Between High Mobility Group Protein B1 and Immune Cells