High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective:To explore the evaluation value of serum levels of positive pentameric protein 3 (PTX3) and creatine kinase isoenzyme MB (CK-MB) on volume load in patients with chronic decompensated heart failure (CDHF).Methods:A total of 300 CDHF patients who visited the Xingtai Central Hospital from July 2019 to July 2022 were selected and divided into a capacity overload group ( n=182) and a non capacity overload group ( n=118) based on their capacity balance level. Two clinical data sets were compared and analyzed. The receiver operating characteristic (ROC) curve was used to analyze the evaluation value of serum PTX3 and CK-MB levels on the volume load of CDHF patients. The clinical disease characteristics of the two groups of patients were analyzed using univariate analysis, and the influencing factors of volume load of CDHF patients were analyzed using logistic regression. A column chart model was constructed and validated. Results:The body mass index (BMI), waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), glycosylated hemoglobin (HbA 1c), C-reactive protein (CRP), uric acid (UA), homeostasis model assessment of insulin resistance (HOMA-IR) of patients in the capacity overload group were higher than those in the non-capacity overload group, and the differences were statistically significant (all P<0.05). The PTX3, CK-MB, pulmonary capillary wedge pressure (PCWP), and CVP levels of patients in the capacity overload group were higher than those in the non-capacity overload group, while albumin, hemoglobin, and hematocrit were lower than those in the non-capacity overload group, and the differences were statistically significant (all P<0.05). The ROC curve showed that the area under the curve (AUC) of PTX3 and CK-MB for predicting capacity overload in CDHF patients are 0.795 and 0.718, with sensitivity of 86.2% and 83.7%, specificity of 65.4% and 68.6%, respectively, indicating high predictive accuracy; The AUC of the two joint predictions is 0.817, the sensitivity was 92.5%, and the specificity was 70.6%. The prediction accuracy was higher than PTX3 ( Z=3.812, P<0.05) and CK-MB ( Z=3.365, P<0.05). PTX3, CK-MB, albumin, hemoglobin, hematocrit, PCWP, and central venous pressure (CVP) were all influencing factors of volume load status in CDHF patients (all P<0.05). The column chart risk prediction model established based on these factors had high accuracy and strong applicability in clinical treatment. Conclusions:Serum PTX3 and CK-MB levels are influencing factors for volume overload in CDHF patients. A column chart model constructed in combination with indicators such as albumin, hemoglobin, hematocrit, PCWP, and CVP has high predictive value for the volume overload status of CDHF.

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

Objective To evaluate the long-term func ti onal outcome of the Gustilo-typeⅢB andⅢC open fractures of the tibia treate d with limb-salvage.Methods Twenty-onepatients,including16cases of Gustil o-tapeⅢB and5cases of ⅢC open fractures of the tibia,were repaired by30f ree vascularized tis-sue flap transfer from1990to1999.The soft tissue and bone defect of 13cases Gustilo-typeⅢB open frac-tures of the tibia wer e repaired simultaneously with osseous-cutaneous flap or musculo-cutaneous-o sseous flap transplantation,the soft tissue defect in3cases of open fractures of the tibia were covered with cutaneous flap or musculo-cu taneous flap at first setting,and the tibia defect or non-union were repaired with vascu lari zed osseous flap at the second.The posterior tibia vessels were reconstructed in all of 5cases of Gustilo-typeⅢC group,in3cases of which posterior tib ial nerve were repaired simultaneously,and emergency cutaneous flap or musculo-cutaneous flap transfer were performed in2cases,delayed vascularized flap tr ansplantation were performed in another3cases.The salvageable limb function w as assessed according to the punos sev en-scale score criteria which includin g freedom of pain,activities of daily life,range of motion,residual deform ity,ra-diographic changes,muscle strength and sensation.Results Twnety-twov ascularized tissue flaps were trans-ferred at first setting in21patients,1 9vascularized tissue flap survived,and other3vascularized tis sue flap failed .The survival rate was86.4%.The average duration from the injury to the f irst vascu larized tis sue flap transplatation was84days.The soft tissue defe ct was completely re paired after the second setting and the fracture or defect was united finally;the average number of procedure for the Gustilo-typeⅢB was4and10for the Gustilo-typeⅢC tibial fractures with an average period fr om injury to bony union of 210and640days in typeⅢB and typeⅢC respective ly.After an average58months of follow-up,ranging from17to129months, 10case obtained excellent and good re sults(62.5%),4cases fair(25 .0%),2cases poor (12.5%)in Gustilo-typeⅢB tibia open fracture.Th ere were no one with excellent,good and fair results,5cases poor (100%) in Gustilo-typeⅢC.Conclusion Theamputation below the knee should be consid-e red for the Gustilo-typeⅢC open fractures of the tibia,especially along wit h the severe injury of the ankle or the dis ruption of poste rior tibial ner ve or the obvious limb shortening.The Gustilo-typeⅢB open frac-tures of t he tibia should deserve reconstruction with the technique of microsurgery,and the functional recov-ery of the salvageable limb was satisfactory.