The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a high-molecular-weight protein complex in the cytoplasm, is composed of three core components: the sensor protein NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and the effector protein caspase-1. It plays a critical role in regulating host immune and inflammatory responses. Studies have shown that the NLRP3 inflammasome has increasingly become a focal point in tumor molecular biology field. A growing body of evidence indicates that the increased expression and activation of the NLRP3 inflammasome is closely associated with the pathogenesis of head and neck squamous cell carcinoma (HNSCC) and the tumor microenvironment (TME). It may promote tumor proliferation, invasion, migration, and other biological behaviors through various regulatory mechanisms while influencing tumor immune evasion and therapy resistance, which holds promise as a prognostic biomarker for patients. This review explores the current effect and mechanism of the NLRP3 inflammasome and its signaling pathways in head and neck cancer, providing insights into clinical targeted drug development and molecular immunotherapy.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Inflammasomes/metabolism* ; Head and Neck Neoplasms/pathology* ; Squamous Cell Carcinoma of Head and Neck/metabolism* ; Tumor Microenvironment ; Signal Transduction ; Animals

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

ObjectiveTo identify the active components in Maimendong decoction (MMDD) against pulmonary fibrosis (PF) and validate their molecular effects in vitro, while focusing on the role of methylophiopogonanone B in regulating fibrosis.MethodsData on MMDD components and targets were gathered from databases including BATMAN-TCM and PubMed, whereas the PF gene data were sourced from GeneCards, OMIM, and TTD. Shared targets were determined using the STRING database, and molecular docking was used to analyze the essential molecules associated with fibrosis. To simulate PF conditions, human embryonic lung fibroblasts (HPF) and A549 cells were exposed to transforming growth factor-β1 (TGF-β1). Various assays were used to determine the effects of MMDD and methylophiopogonanone B on signaling pathways, apoptosis, and epithelial–mesenchymal transition.ResultsWe identified 11 active components from MMDD extracts that targeted 511 shared proteins associated with PF, revealing 10 key targets in network analysis. Gene ontology analysis indicated that processes and pathways such as apoptosis regulation and PI3K/Akt signaling were involved. In vitro experiments revealed that MMDD downregulated the expression of α-smooth muscle actin (α-SMA), collagen type I (COL-I), and collagen type III and regulated Bcl-2/Bax signaling pathways to promote apoptosis. The flow cytometry apoptosis assay revealed that MMDD promoted the TGF-β1-induced apoptosis of myofibroblasts. The primary active ingredient in MMDD, methylophiopogonanone B, reduced α-SMA, COL-I, and PI3K/Akt/mTOR-related protein levels in TGF-β1-treated HPF cells, decreased Bcl-2 and cleaved caspase 3, and increased Bax. Moreover, methylophiopogonanone B increased E-cadherin levels and reduced α-SMA, fibronectin, N-cadherin, vimentin, and snail in TGF-β1-treated A549 cells.ConclusionMethylophiopogonanone B demonstrated the potential to treat PF by inducing myofibroblast apoptosis and inhibiting EMT. However, despite encouraging initial results, further clinical research is warranted to verify the safety and efficacy of methylophiopogonanone B in the management of PF

AIM:To explore the therapeutic effect of Tongfeng-Qingli mixture(TFQLM)and its mechanism in hyperuricemic(HUA)rats based on uric acid(UA)transporter and Janus kinase 2(JAK2)/signal transducer and acti-vator of transcription 3(STAT3)signaling pathway.METHODS:(1)In vivo experiment:36 male SD rats were random-ly divided into control(CON)group,model(MOD)group,benzbromarone(BEN)group,low-dose TFQLM(TFQLM-L)group,medium-dose TFQLM(TFQLM-M)group,and high-dose TFQLM(TFQLM-H)group,with 6 rats in each group.In all groups except CON group,HUA was induced in rats by giving hypoxanthine(HP)combined with potassium oxybate(OP)for 35 consecutive days.The rats in CON group were given sodium carboxymethyl cellulose solution by gavage.A fully automatic biochemistry analyzer was used to detecte serum UA,serum creatinine(SCr)and blood urea nitrogen(BUN)levels.The xanthine oxidase(XOD)and adenosine deaminase(ADA)levels in the liver were detected by ELISA kits.The histopathological changes of kidneys were observed by HE staining.Immunohistochemistry was performed to de-tect urate transporter 1(URAT1)and glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and OAT3 ex-pression in the kidney.Western blot was used to measure the protein levels of URAT1,GLUT9,OAT1,OAT3,interleu-kin-6(IL-6),tumor necrosis factor-α(TNF-α),JAK2,p-JAK2,STAT3,p-STAT3 and repressor of cytokine signaling 3(SOCS3)in the kidney.(2)In vitro experiments:HUA cellular model was established by UA stimulation in HK2 cells,and the protein levels of URAT1,GLUT9,OAT1,OAT3,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3,and SOCS3 were detected by Western blot.RESULTS:Compared with MOD group,serum UA,SCr and BUN levels of the rats in all TFQLM groups were reduced(P<0.05).The XOD and ADA levels in liver tissues were significantly reduced(P<0.05).The protein levels of URAT1,GLUT9,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were decreased(P<0.05),and OAT1 and OAT3 protein expression was increased(P<0.05)in kidneys and HK2 cells.CONCLUSION:By establishing rat and HK2 cell HUA models,it is hypothesized that TFQLM may reduce UA levels and attenuate renal inflammation in HUA rats,and its mechanism may be related to the regulation of UA transport proteins and inhibition of the JAK2/STAT3 signaling pathway.

Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

AIM:To explore the therapeutic effect of Tongfeng-Qingli mixture(TFQLM)and its mechanism in hyperuricemic(HUA)rats based on uric acid(UA)transporter and Janus kinase 2(JAK2)/signal transducer and acti-vator of transcription 3(STAT3)signaling pathway.METHODS:(1)In vivo experiment:36 male SD rats were random-ly divided into control(CON)group,model(MOD)group,benzbromarone(BEN)group,low-dose TFQLM(TFQLM-L)group,medium-dose TFQLM(TFQLM-M)group,and high-dose TFQLM(TFQLM-H)group,with 6 rats in each group.In all groups except CON group,HUA was induced in rats by giving hypoxanthine(HP)combined with potassium oxybate(OP)for 35 consecutive days.The rats in CON group were given sodium carboxymethyl cellulose solution by gavage.A fully automatic biochemistry analyzer was used to detecte serum UA,serum creatinine(SCr)and blood urea nitrogen(BUN)levels.The xanthine oxidase(XOD)and adenosine deaminase(ADA)levels in the liver were detected by ELISA kits.The histopathological changes of kidneys were observed by HE staining.Immunohistochemistry was performed to de-tect urate transporter 1(URAT1)and glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and OAT3 ex-pression in the kidney.Western blot was used to measure the protein levels of URAT1,GLUT9,OAT1,OAT3,interleu-kin-6(IL-6),tumor necrosis factor-α(TNF-α),JAK2,p-JAK2,STAT3,p-STAT3 and repressor of cytokine signaling 3(SOCS3)in the kidney.(2)In vitro experiments:HUA cellular model was established by UA stimulation in HK2 cells,and the protein levels of URAT1,GLUT9,OAT1,OAT3,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3,and SOCS3 were detected by Western blot.RESULTS:Compared with MOD group,serum UA,SCr and BUN levels of the rats in all TFQLM groups were reduced(P<0.05).The XOD and ADA levels in liver tissues were significantly reduced(P<0.05).The protein levels of URAT1,GLUT9,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were decreased(P<0.05),and OAT1 and OAT3 protein expression was increased(P<0.05)in kidneys and HK2 cells.CONCLUSION:By establishing rat and HK2 cell HUA models,it is hypothesized that TFQLM may reduce UA levels and attenuate renal inflammation in HUA rats,and its mechanism may be related to the regulation of UA transport proteins and inhibition of the JAK2/STAT3 signaling pathway.

Objective To study the effects of radiation on the morphology,function,and NLRP3 expression of mouse salivary gland tissue,and provide new ideas to repair radiation-induced damage to salivary gland tissue.Methods We established a mouse model of radiation-induced submandibular gland injury and Recorded the weight of drinking water.The salivary flow rate was assessed,and HE staining was used to observe submandibular gland injury.Immunohistochemistry and Real-time PCR were used to assess expression of NLRP3 and Caspase-1 in the radiation-injured submandibular gland of mice at 1,3,7 and 14 days after radiation exposure.Results Over time,the amount of water consumed by radiation group mice was gradually increased,the salivary flow rate was decreased,and inflammatory cells in the submandibular gland continued to increase.Acinar cells gradually showed lesions,such as nuclear pyknosis and vacuolization.At 7 and 14 days after radiation exposure,expression levels of NLRP3 and Caspase-1 proteins and genes in the radiation group were significantly higher than those in the normal group(P＜0.05).Conclusions Radiation damages mouse submandibular gland tissue and activates the NLRP3 inflammasome to increase its expression level.

Objective To explore the value of machine learning(ML)models based on non-contrast CT(NCCT)radiomics features for predicting the severity of acute phase traumatic brain injury(TBI).Methods Totally 600 TBI patients were retrospectively collected as observation group,other 65 TBI patients were taken as external validation set,while 50 TBI patients were prospectively enrolled as prospective validation set.Patients in observation group were divided into high-risk subgroup(n=240)and low-risk subgroup(n=360)according to Glasgow outcome scale(GOS)at discharge.The severity of acute phase TBI in observation group was assessed by doctor A and B with the same criteria,then an artificial model was established based on clinical and NCCT data at the time of first diagnosis using logistic regression(LR)method for predicting the severity of acute phase TBI.Patients in observation group were divided into training set(n=420,including 168 in high-risk subgroup and 252 in low-risk subgroup)and test set(n=180,including 72 in high-risk subgroup and 108 in low-risk subgroup)at the ratio of 7∶3.Based on NCCT of training set,radiomics features were extracted and selected,and LR,support vector machine(SVM),random forest(RF)and K-nearest neighbor(KNN)were used to establish 4 ML models.The efficacies of the above models were validated in test set,external validation set(including 34 cases of high-risk and 31 cases of low-risk TBI)and prospective validation set(including 21 cases of high-risk and 29 cases of low-risk TBI),respectively.Results The area under the curve(AUC)of doctor A and B for evaluating the severity of acute phase TBI in observation group was 0.606 and 0.771,respectively,of artificial model was 0.824.Based on NCCT in training set,6 optimal radiomics features were selected to construct LR,SVM,RF and KNN ML models,with AUC of 0.983,0.971,0.970 and 0.984 in test set,respectively,while the AUC of artificial model was 0.708.The AUC of LR,SVM,RF,KNN ML models and artificial model in external validation set was 0.879,0.881,0.984,0.863 and 0.733,while in prospective validation set was 0.984,0.873,0.982,0.897 and 0.704,respectively.Conclusion ML models based on CT radiomics could effectively predict the severity of acute phase TBI.

Objective:To translate the Cumulated Ambulation Score (CAS) into Chinese and test its reliability and validity in elderly inpatients, to provide a basis for assessing elderly inpatients′ basic mobility during hospitalization.Methods:This was a cross-sectional study. After obtaining the authorization of the original author, the Chinese version of CAS was formed by WHO′s cross-cultural translation process. A total of 414 hospitalized elderly inpatients from Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and Shanghai Yangpu District Kongjiang Hospital were selected between March and September 2021. Cronbach′s α coefficient was used to test internal consistency, linear weighted Kappa was employed to assess inter-rater reliability, and concurrent validity was examined using items related to mobility of Barthel Index scores as a reference standard.Results:Of the 414 patients, 221 were males and 193 were females, and the patients aged (76.67 ± 9.98) years old; 122 cases (29.5%) had a perfect score of 6 with normal basic mobility, 89 cases (21.5%) had a score of 0 with complete loss of mobility, and the remaining 203 patients had a score of 1-5 with varying degrees of reduced mobility. The Chinese version of CAS demonstrated good assessment performance for basic mobility in elderly inpatients with a Cronbach′s α coefficient of 0.952. Weighted Kappa values for individual items and total scores showed excellent agreement among raters (>0.85), while concurrent validity yielded a value of 0.935 ( P<0.01) when compared with Barthel Index scores.Total score of CAS was significantly correlated with item scores and total score of Barthel index ( r values were 0.423 to 0.944, all P<0.01). Conclusions:The Chinese version of CAS has good reliability and validity. The items are concise, clear and easy to understand. It is suitable as a preliminary screening tool for clinical departments to evaluate the basic mobility of elderly inpatients.