Sneddon syndrome is a rare neurocutaneous disorder that primarily affects small-and medium-sized arteries.Its clinical manifestations include livedo racemosa and recurrent cerebral ischemic events,and it may also involve multiple organs such as the heart,spleen,and kidneys.This disease can lead to early-onset stroke,making it a rare cause of stroke in young adults.This article reported a case of a young female patient who experienced two cerebral infarctions within one month.Genetic testing identified a homozygous mutation in the adenosine deaminase 2 gene,confirming the diagnosis of Sneddon syndrome.This case serves as a reference to improve clinical recognition of this disease.

OBJECTIVES: To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry. RESULTS: In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis. CONCLUSIONS DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Colitis, Ulcerative/metabolism* ; Dextran Sulfate/adverse effects* ; Male ; Inflammasomes/metabolism* ; Mice ; Benzoquinones/therapeutic use* ; Th17 Cells ; Caspase 1/metabolism*

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Aim To explore the relationship between serum uric acid(UA)/creatinine(Cr),homocysteine(Hcy),apolipoprotein A1(ApoA1)levels and plaque stability in patients with carotid atherosclerosis(CAS)and the pre-dictive value for secondary acute cerebral infarction(ACI).Methods 138 patients with CAS were selected as the re-search subjects and further divided into stable plaque group and unstable plaque group based on the stability of plaques.Heathy individuals undergoing physical examinations were selected as the control group.Enzyme cycling method was used to detect Hcy level,latex enhanced immunoturbidimetry method was used to detect ApoA1 level,uricase method was used to detect UA level,enzyme method was used to detect Cr level,and UA/Cr ratio was calculated.Baseline data and labo-ratory indicators in the no plaque group,stable plaque group and unstable plaque group were compared.The relationship between laboratory indicators and intima-media thickness(IMT)was analyzed using Spearman correlation analysis.Cox regression model was used for univariate and multivariate analysis of secondary ACI in patients with CAS,and ROC curve was used to evaluate the predictive value of serum UA/Cr,Hcy and ApoA1 levels for it.Results Among 138 patients with CAS,there were 74 cases in the stable plaque group and 64 cases in the unstable plaque group;there were 46 cases of secondary ACI.There were 42 cases in the control group.Compared with the control group,the stable plaque group and unstable plaque group had lower levels of serum ApoA1 and high density lipoprotein cholesterol(HDLC),and higher levels of serum UA/Cr,Hcy,low density lipoprotein cholesterol(LDLC)and IMT(P＜0.05).Spearman correlation analysis showed that IMT in the plaque group was positively correlated with serum UA/Cr and Hcy levels(r=0.535 and r=0.681,P＜0.05),and negatively correlated with ApoA1 levels(r=-0.594,P＜0.05).Cox regression analysis showed that un-stable plaques,high serum UA/Cr and Hey levels were risk factors for secondary ACI,while high serum ApoA1 levels were protective factors for secondary ACI(P＜0.05).ROC curve analysis showed that the sensitivity and specificity of combi-ning serum UA/Cr,Hcy and ApoA1 for predicting secondary ACI in the CAS patients were 85.45％and 82.67％,respec-tively,with an AUC of 0.920,which was higher than the individual diagnosis of UA/Cr,Hcy and ApoA1.Conclu-sions The levels of serum UA/Cr and Hcy are significantly positively correlated with plaque formation and stability in the CAS patients,while ApoA1 is significantly negatively correlated with them.These three factors are independent influen-cing factors for secondary ACI in the CAS patients,and their combined prediction of ACI has a higher efficacy.

Neurodegenerative diseases are chronic and progressive diseases of the nervous system.Modern studies have shown that intestinal flora disorders,mitochondrial dysfunction and lipid metabolism abnormalities are closely related to the occurrence and development of neurodegenerative diseases,but the treatment methods are limited.Traditional Chinese medicine believes that spleen is the"the foundation of nurture"and the"the source of Qi and blood biochemistry",Qi deficiency leads to insufficient Qi,blood and body fluid metaplasia,brain dysplasia,leading to the occurrence of neurodegenerative diseases.This paper discusses the mechanism of treating neurodegenerative diseases by spleen from the perspective of"intestinal flora,mitochondria and lipids",and concludes that intestinal flora balance is the material basis of spleen function,mitochondrial homeostasis is an important mechanism of the function of"spleen governing transportation and transformation",and abnormal lipid metabolism is an important manifestation of spleen deficiency and phlegm stasis.Intestinal flora,mitochondria and lipid metabolism may be the potential biological basis for the treatment of neurodegenerative diseases by spleen in traditional Chinese medicine.In order to provide ideas for the clinical research and treatment of neurodegenerative diseases.

Neurodegenerative diseases are chronic and progressive diseases of the nervous system.Modern studies have shown that intestinal flora disorders,mitochondrial dysfunction and lipid metabolism abnormalities are closely related to the occurrence and development of neurodegenerative diseases,but the treatment methods are limited.Traditional Chinese medicine believes that spleen is the"the foundation of nurture"and the"the source of Qi and blood biochemistry",Qi deficiency leads to insufficient Qi,blood and body fluid metaplasia,brain dysplasia,leading to the occurrence of neurodegenerative diseases.This paper discusses the mechanism of treating neurodegenerative diseases by spleen from the perspective of"intestinal flora,mitochondria and lipids",and concludes that intestinal flora balance is the material basis of spleen function,mitochondrial homeostasis is an important mechanism of the function of"spleen governing transportation and transformation",and abnormal lipid metabolism is an important manifestation of spleen deficiency and phlegm stasis.Intestinal flora,mitochondria and lipid metabolism may be the potential biological basis for the treatment of neurodegenerative diseases by spleen in traditional Chinese medicine.In order to provide ideas for the clinical research and treatment of neurodegenerative diseases.

Aim To explore the relationship between serum uric acid(UA)/creatinine(Cr),homocysteine(Hcy),apolipoprotein A1(ApoA1)levels and plaque stability in patients with carotid atherosclerosis(CAS)and the pre-dictive value for secondary acute cerebral infarction(ACI).Methods 138 patients with CAS were selected as the re-search subjects and further divided into stable plaque group and unstable plaque group based on the stability of plaques.Heathy individuals undergoing physical examinations were selected as the control group.Enzyme cycling method was used to detect Hcy level,latex enhanced immunoturbidimetry method was used to detect ApoA1 level,uricase method was used to detect UA level,enzyme method was used to detect Cr level,and UA/Cr ratio was calculated.Baseline data and labo-ratory indicators in the no plaque group,stable plaque group and unstable plaque group were compared.The relationship between laboratory indicators and intima-media thickness(IMT)was analyzed using Spearman correlation analysis.Cox regression model was used for univariate and multivariate analysis of secondary ACI in patients with CAS,and ROC curve was used to evaluate the predictive value of serum UA/Cr,Hcy and ApoA1 levels for it.Results Among 138 patients with CAS,there were 74 cases in the stable plaque group and 64 cases in the unstable plaque group;there were 46 cases of secondary ACI.There were 42 cases in the control group.Compared with the control group,the stable plaque group and unstable plaque group had lower levels of serum ApoA1 and high density lipoprotein cholesterol(HDLC),and higher levels of serum UA/Cr,Hcy,low density lipoprotein cholesterol(LDLC)and IMT(P＜0.05).Spearman correlation analysis showed that IMT in the plaque group was positively correlated with serum UA/Cr and Hcy levels(r=0.535 and r=0.681,P＜0.05),and negatively correlated with ApoA1 levels(r=-0.594,P＜0.05).Cox regression analysis showed that un-stable plaques,high serum UA/Cr and Hey levels were risk factors for secondary ACI,while high serum ApoA1 levels were protective factors for secondary ACI(P＜0.05).ROC curve analysis showed that the sensitivity and specificity of combi-ning serum UA/Cr,Hcy and ApoA1 for predicting secondary ACI in the CAS patients were 85.45％and 82.67％,respec-tively,with an AUC of 0.920,which was higher than the individual diagnosis of UA/Cr,Hcy and ApoA1.Conclu-sions The levels of serum UA/Cr and Hcy are significantly positively correlated with plaque formation and stability in the CAS patients,while ApoA1 is significantly negatively correlated with them.These three factors are independent influen-cing factors for secondary ACI in the CAS patients,and their combined prediction of ACI has a higher efficacy.

Sneddon syndrome is a rare neurocutaneous disorder that primarily affects small-and medium-sized arteries.Its clinical manifestations include livedo racemosa and recurrent cerebral ischemic events,and it may also involve multiple organs such as the heart,spleen,and kidneys.This disease can lead to early-onset stroke,making it a rare cause of stroke in young adults.This article reported a case of a young female patient who experienced two cerebral infarctions within one month.Genetic testing identified a homozygous mutation in the adenosine deaminase 2 gene,confirming the diagnosis of Sneddon syndrome.This case serves as a reference to improve clinical recognition of this disease.

Cerebral ischemia reperfusion injury(CIRI)is a secondary brain injury that may occur in patients with ischemic stroke during the process of blood flow recovery.NOD-like receptor protein 3(NLRP3)inflammasome plays an important role in the occurrence and development of CIRI.Regulating the activity of NLRP3 inflammasome can induce cell pyroptosis,induce neuroinflammatory response,promote macrophage/microglial polarization,destroy the blood-brain barrier,affect angiogenesis and neurogenesis,thereby affecting CIRI.Traditional Chinese medicine has obvious advantages in the treatment of CIRI.In this paper,with NLRP3 inflammasome as the core,we systematically elucidated the mechanism of action of traditional Chinese medicines on CIRI,and found that traditional Chinese medicines monomers(such as baicalin,polygalasaponin F)and traditional Chinese medicines compound formulas(such as Huangqi guizhi wuwu decoction,Yiqi shengqing formulation)can inhibit NLRP3 inflammasome activity,reduce inflammatory response and oxidative stress,and improve neuronal injury,thereby reducing CIRI.

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.