Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the expression levels of FOXO1 and SMAD4 in esophageal cancer (EC) tissues and their associations with clinicopathological features and prognosis. Methods Tissue samples of cancerous and adjacent non-cancerous tissues were collected from 131 EC patients. Hematoxylin-eosin (HE) staining was performed to observe the pathological morphology of EC and adjacent tissues. The mRNA expression of FOXO1 and SMAD4 was measured using quantitative real-time polymerase chain reaction (qRT-PCR), while the protein expression of FOXO1 and SMAD4 was determined by immunohistochemistry; Spearman's correlation analysis was employed to assess the correlation between FOXO1 and SMAD4 protein expression in EC tissues; Cox regression analysis was conducted to analyze factors influencing the prognosis of EC patients; Kaplan-Meier analysis was used to perform survival analysis for EC patients. Results The expression of FOXO1 mRNA and its protein positive expression rate were significantly higher in the EC tissues than those in the adjacent tissues, whereas the expression of SMAD4 mRNA and its protein positive expression rate were significantly lower (P < 0.05). FOXO1 and SMAD4 were associated with tumor diameter, tumor differentiation, lymph node metastasis and TNM stage (P < 0.05). A negative correlation was observed between FOXO1 and SMAD4 protein expression in EC tissues (r=-0.419, P < 0.05). FOXO1, SMAD4, tumor diameter, differentiation, lymph node metastasis and TNM stage were identified as factors influencing mortality in EC patients (P < 0.05). The 3-year overall survival rate of EC patients was 84.73% (111/131). The 3-year cumulative survival rate was significantly lower in the EC patients with positive FOXO1 expression than in thosewith negative FOXO1 expression (P < 0.05), while it was significantly higher in patients with positive SMAD4 expression than in those with negative SMAD4 expression (P < 0.05). Conclusion The positive expression rate of FOXO1 is higher, while that of SMAD4 is lower in EC tissues. Their protein expressions were associated with clinicopathological features and prognosis in EC patients. FOXO1 and SMAD4 may serve as important biomarkers for predicting the prognosis of EC.

Since the global COVID-19 pandemic, SARS-CoV-2 infection, which causes COVID-19, has been associated with a range of diseases whose atypical manifestations have been increasingly reported. The mild encephalitis or encephalopathy associated with reversible corpus callosum lesions or mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare clinical and radiographic syndrome. At present, the pathogenesis of MERS caused by COVID-19 is still unclear, and its pathogenesis may include hypoxic damage, inflammatory response, immune disorders, changes in osmotic pressure, excitatory amino acid toxicity, oxidative stress and functional abnormalities of renin-angiotensin system. This paper reports a case of severe COVID-19 complicated with MERS, and discusses the pathogenesis from a pathophysiological point of view.

Objective:To investigate the awareness of diabetes knowledge among the health examination population and its influencing factors.Methods:A cross-sectional study. From september to november 2022, the subjects of six health examination centers located in six different cities (Beijing, Shanghai, Tianjin, Chongqing, Xiamen, Hangzhou) in China were investigated in the form of questionnaires to investigate the awareness of diabetes core information and the level of trust to different information sources of diabetes knowledge. According to the questionnaire results, the subjects were divided into a high awareness group of diabetes core information and a low awareness group. Logistic regression was used to analyze the influencing factors of diabetes core information awareness; the t-test was used to compare the trust degree of the two groups to different information sources. Results:A total of 9 315 people were included in the six centers, including 4 932 men (52.90%) with an average age of (39.36±12.64) years and 4 383 women (47.10%) with a mean age of (37.47±11.85) years. Only 36% of the people had high awareness of diabetes core information; variables such as gender, age, education level, physical examination frequency in the past three years, package price of this physical examination, self-evaluation of diabetes knowledge, diabetes status, and city of residence were variables that affect the level of awareness of core information related to diabetes (all P<0.05). Compared with the low awareness group of diabetes core information, the high awareness group trusted professional medical staff ( t=-9.597, P<0.05) and community health promotion more ( t=-5.014, P<0.05), but did not trust the emerging popular science propaganda means, such as WeChat official accounts/WeChat groups/QQ groups, Internet web page, Tiktok/Kwai and other short video APPs. Conclusion:The awareness rate of diabetes knowledge among the health examination population is low, and it is affected by many factors; Health education on diabetes knowledge should be carried out for people undergoing physical examination.

Radiotherapy, as a common modality for the treatment of head and neck cancer (HNC), frequently induces oral and maxillofacial complications. However, the complex tissues and diverse pathogeneses of these regions lead to limited treatment protocols and research progress currently. This paper systematically summarizes radiation-induced oral mucositis, salivary gland injury, and dental caries in radiotherapy for HNC and reviews existing pathogenetic hypotheses, treatment, and research progress. The purpose is to provide some reference for further research on relevant pathological mechanisms and the development of new preventive and treatment methods.

BACKGROUND: The hepatitis B virus (HBV) vaccine has been efficiently used for decades. However, hepatocellular carcinoma caused by HBV is still prevalent globally. We previously reported that interferon (IFN)-induced tripartite motif-containing 25 (TRIM25) inhibited HBV replication by increasing the IFN expression, and this study aimed to further clarify the anti-HBV mechanism of TRIM25. METHODS: The TRIM25-mediated degradation of hepatitis B virus X (HBx) protein was determined by detecting the expression of HBx in TRIM25-overexpressed or knocked-out HepG2 or HepG2-NTCP cells via Western blotting. Co-immunoprecipitation was performed to confirm the interaction between TRIM25 and HBx, and colocalization of TRIM25 and HBx was identified via immunofluorescence; HBV e-antigen and HBV surface antigen were qualified by using an enzyme-linked immunosorbent assay (ELISA) kit from Kehua Biotech. TRIM25 mRNA, pregenomic RNA (pgRNA), and HBV DNA were detected by quantitative real-time polymerase chain reaction. The retinoic acid-inducible gene I (RIG-I) and pgRNA interaction was verified by RNA-binding protein immunoprecipitation assay. RESULTS: We found that TRIM25 promoted HBx degradation, and confirmed that TRIM25 could enhance the K90-site ubiquitination of HBx as well as promote HBx degradation by the proteasome pathway. Interestingly, apart from the Really Interesting New Gene (RING) domain, the SPRY domain of TRIM25 was also indispensable for HBx degradation. In addition, we found that the expression of TRIM25 increased the recognition of HBV pgRNA by interacting with RIG-I, which further increased the IFN production, and SPRY, but not the RING domain is critical in this process. CONCLUSIONS The study found that TRIM25 interacted with HBx and promoted HBx-K90-site ubiquitination, which led to HBx degradation. On the other hand, TRIM25 may function as an adaptor, which enhanced the recognition of pgRNA by RIG-I, thereby further promoting IFN production. Our study can contribute to a better understanding of host-virus interaction.
Humans ; Hepatitis B virus ; DEAD Box Protein 58/metabolism* ; RNA ; Liver Neoplasms ; Virus Replication ; Tripartite Motif Proteins/genetics* ; Transcription Factors ; Ubiquitin-Protein Ligases/genetics*

The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.

The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.
Animals ; Cellular Reprogramming ; Nerve Regeneration ; Neurogenesis ; Neuroglia ; Neurons

Objective To investigate the effects of G-CSF-mobilized autologous stem cells in the prevention of radiation pulmonary injury.Methods Mice were divided into control group,irradiation group and treatment group.Mouse model of pulmonary fibrosis was established by exposing chest to a single dose of 14 Gy.Animals in the treatment group received recombinant human G-CSF (250 μg/kg daily for 5 d) before the irradiation in order to mobilize autologous stem cells in vivo.The general condition and mortality were documented after radiation injury.The pathological study with histological scoring,Masson staining and Sirius red staining with polarized light analysis were used to identify lung injury and the potential benefit of stem cell mobilization.Results Local chest irradiation of a single dose of 14 Gy was a suitable dose to create radiation-induced pulmonary fibrosis in mice.The death rate was 37.5％,which mainly happened around 11 weeks after injury.In contrast,all of the animals in G-CSF treated group survived.The ratio of lung to body mass was significantly increased in both irradiation group and treatment group (F =23.20,P＜0.05) around 3 months after the injury,with a higher ratio in irradiation group than that in treatment group (P＜0.05).Histological scoring for alveolar inflammation at 3 months after injury revealed statistically significant difference in irradiation group and treatment group compared with control group (F=11.93,P＜ 0.05).At this time point,the pathological observation showed lung tissue degeneration and necrosis with alveolitis and interstitial inflammation,as well as fibroblasts proliferation and focal collagen deposition in alveolar septa.At 4 month after the injury,the inflammation ininterstitial tissue was receded,but fibrosis and collagen deposition were significantly increased.In addition,at 3 and 4 months afterinjury,the pulmonary fibrosis was aggravated in irradiation group (F=28.73,16.85,P＜0.05),and significantly alleviated in the treatment group (P＜0.05).The similar results were confirmed in collagen content analysis (IOD) by Sirius red staining and image analysis (F =17.70,17.79,P＜ 0.05).Conclusions Autologous mobilization of stem cells could prevent the death of radiation-injured animals possibly by alleviating early lung injury and interstitial inflammation as well as the late pulmonary fibrosis,suggesting a therapeutic potential of autologous stem cell mobilization in radiation pulmonary fibrosis.