Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Sepsis-acquired weakness (SAW) is a common complication in critically ill patients, yet significant gaps remain in both mechanistic understanding and therapeutic interventions for this condition. SAW not only prolongs the duration of mechanical ventilation and hospitalization but is also closely associated with increased mortality. Even if these SAW patients survive, they often experience long-term physical dysfunction after hospital discharge, leading to diminished quality of life. Emerging evidence suggests that sustained mitochondrial dysfunction may constitute a pivotal pathophysiological basis for the development and progression of SAW, primarily encompassing five key aspects: dysregulated mitochondrial quality control (MtQC), impaired oxidative phosphorylation (OXPHOS), exacerbated oxidative stress, disrupted Ca²⁺; homeostasis, and their mediation of diverse myofiber injuries. This article systematically elucidates the central role of mitochondrial dysfunction in the pathogenesis of SAW. Furthermore, we explore potential therapeutic strategies targeting mitochondrial function, including mitigating mitochondrial oxidative stress, optimizing nutritional support, and supplementing with muscle-derived mesenchymal stem cells. These insights provide a critical theoretical framework for understanding SAW mechanisms and developing clinical interventions, with particular emphasis on the translational value of mitochondrial-targeted therapies in improving outcomes for septic patients.
Humans ; Sepsis/metabolism* ; Mitochondria/metabolism* ; Muscle Weakness/etiology* ; Oxidative Stress ; Oxidative Phosphorylation

Objective: To investigate the molecular mechanisms and pathways of action of total flavonoids of Dracocephalum moldavica L.(TFDM) in treating vascular cognitive impairment(VCI) based on network pharmacology and in vivo animal experiments. Methods : The swiss target prediction database, literature, and PubChem were used to screen the active components and action targets of TFDM. The online mendelian inheritance in man(OMIM) and GeneCards databases were utilized to screen for possible VCI targets. Venny software was used to obtain the intersection target of TFDM and VCI. The search tool for recurring instances of neighbouring genes(String) database and Cytoscape software was used to construct the PPI network. The database for annotation, visualization and integrated discovery(DAVID) database was utilized to screen for the kyoto encyclopedia of genes and genomes(KEGG) pathway and gene ontology(GO) enrichment analyses to explore the molecular mechanism and signaling pathway of TFDM for VCI. 24 rats were divided into Sham, Model, Donepezil, and TFDM groups. Except for the Sham group, the VCI model was created using modified bilateral common carotid artery ligation. After continuous gavage for 21 days, the Morris water maze test was used to evaluate the spatial learning and memory ability of rats. Hematoxy-lineosin(HE) staining was used to observe the pathological changes in the hippocampal CA1 and cortex region of the animals and immunohistochemistry detection of zonula occludens-1(ZO-1) content in the brains of the rats. Western blot was used to detect nuclear factor kappa-B p65(NF-κB p65) and tumor necrosis factor-α(TNF-α) in rat brains. Results : A total of 39 active ingredients of TFDM were screened, 209 corresponding targets, 10 417 gene targets of VCI, and 193 intersecting targets. According to the results of the GO enrichment of function analysis, TFDM could improve the response of reactive oxygen species and metabolic processes of reactive oxygen species, etc. KEGG pathway enrichment analysis suggested that TFDM might regulate TNF, IL-17 signing pathway, etc. The results of animal experiments showed that TFDM improved learning and memory while reduced pathological damage in the brains of VCI rats. In addition, TFDM upregulated the positive expression of ZO-1 and downregulated the protein levels of TNF-α and NF-κB p65(P<0.05). Conclusion TFDM can improve the cognitive function of VCI through multi-components and multi-targets, and its key mechanism may be related to inhibiting TNF-α/NF-κB p65 signaling pathway,reducing neuroinflammation,and improvement of blood-brain barrier permeability.

Amino acids are essential nutrients for the survival of all cells in the body,and their metabolic processes are closely associ-ated with tumor development and progression.The metabolic changes of the essential amino acid tryptophan have a significance impact on tumor microenvironment.Tryptophan is mainly metabolized to kynurenine(KYN)by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase,and the accumulation of KYN and the deficiency of tryptophan cause alterations in the immune status in tumor micro-environment,which in turn affects tumor development and progression.Based on the current studies on tryptophan,this article system-atically discusses the influence of abnormal tryptophan metabolism on tumors and the interventions targeting this pathway,in order to provide a reference for subsequent tumor therapy.

Tumor microenvironment(TME)is the cellular environment for tumor development,growth,and metastasis.Adenosine(ADO)is an immunosuppressive metabolic product that is continuously upregulated in TME,with various types and wide distribution of receptors.The complex and dynamic interactions between ADO and tumor cells constantly influence tumor progression.ADO can di-rectly or indirectly promote tumor development and progression by promoting tumor generation and metastasis,mediating the immune escape of tumor,and modulating tumor-infiltrating immune cells.Based on the characteristics of ADOs in TME,this article reviews the latest advances in the dynamic alterations of ADO in TME,in order to provide insights into tumor treatment targeting the ADO pathway.

Cholesterol,as an important component of cell membranes,plays a multifaceted role in mediating tumor immunomodulation and drug intervention.In case of cholesterol metabolic imbalance,the accumulation of cholesterol metabolic intermediates,the changes in concentrations,and the regulation of related signaling pathways can affect tumor immunity by promoting inflammation and inhibiting immune cell function.Preclinical and clinical studies have shown that controlling cholesterol metabolism can inhibit tumor growth,re-shape body immune regulation,and enhance antitumor immunity.A deep understanding of the association between immune cells and cholesterol metabolic pathways in the tumor microenvironment can help to develop novel drugs targeting cholesterol metabolism.This article reviews the multifaceted role of cholesterol and its derived metabolites in the tumor microenvironment by regulating various types of immune cells such as myeloid-derived suppressor cells,tumor-associated macrophages,dendritic cells,and T-lymphocytes,as well as the characteristics of tumor immunomodulation mediated by cholesterol metabolism and the advances in pharmaceutical re-search on improving the immune function of the body by intervening against cholesterol,in order to further provide new ideas and a thera-peutic basis for cholesterol modulation and intervention in tumor im-munotherapy.

Flow diverter (FD) can significantly improve the occlusion rate and reduce the recurrence rate of intracranial aneurysms, and has become an irreplaceable endovascular treatment option. Delayed aneurysm rupture (DAR) is one of the most serious complications after FD implantation, with a very high mortality rate. It is a major challenge to the safety of FD implantation. The mechanism of DAR is currently not fully understood and may be associated with the changes in hemodynamics after FD implantation, inflammation and mechanical stress within aneurysms, and changes in postoperative coagulation function. This article reviews the research progress on the occurrence mechanism of DAR and outlines future research directions, with the aim of reducing DAR occurrence and optimizing clinical decision-making.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

Background Acne treatment cycle lasts long and will cause facial appearance damage.Many patients are prone to psychological problems and severe patients may even experience suicidal ideation.However,the influencing factors of psychological health problems in acne patients are still unclear.Objective To investigate the mental health status of patients with moderate-to-severe acne and to analyze the influencing factors of their psychological health problems,so as to provide references for improving their mental health.Methods A total of 120 patients with moderate-to-severe acne of grades II-IV were selected as the research subjects,who were treated in the dermatology outpatient department of the Third Hospital of Mianyang from June 2021 to June 2023.All subjects were evaluated by using the Acne-Specific Quality of Life Questionnaire(Acne-QoL),Self-rating Depression Scale(SDS),Self-rating Anxiety Scale(SAS),Rosenberg Self-Esteem Scale(RSES)and Social Phobia Inventory(SPIN).According to the evaluation results of SDS,SAS,RSES,SPIN,subjects were divided into a group with mental health problems(n=21)and a group without mental health problems(n=99).Binary Logistic regression anaylsis was adopted to explore the influencing factors of psychological health problems in acne patients.Results A total of 21 patients(17.50%)were detected to have symptoms of depression,anxiety,inferiority or social dysfunction.Statistically significant difference was observed in comparison between two groups in gender,profession,acne classification,dietary habit,age,illness course as well as the factor scores of self perception,emotional function,social function and acne symptom in Acne-QoL(χ2=7.013,23.123,9.028,11.327,t=9.913,13.022,4.081,5.383,5.361,10.203,P<0.05).The results of binary Logistic regression analysis showed that the followings were risk factors for the occurrence of psychological health problems in acne patients:female(OR=2.243,95%CI:1.136～4.429),acne of grade III(OR=3.615,95%CI:1.269～10.295)or IV(OR=1.872,95%CI:1.073～3.266),course of disease≥1.6 years(OR=2.499,95%CI:1.068～5.851),a spicy or greasy diet(OR=3.811,95%CI:1.169～12.427),Acne-QoL self perception score≤18(OR=1.802,95%CI:1.227～2.646),Acne-QoL emotional function score≤18(OR=2.252,95%CI:1.016～4.992),Acne-QoL social function score≤14(OR=3.515,95%CI:1.534～8.053)and Acne-QoL acne symptom score≤18(OR=3.586,95%CI:1.098～11.715).Protective factors for psychological health problems in acne patients included age over 30 years old(OR=0.429,95%CI:0.283～0.648),occupation as professional cadre or enterprise employee(OR=0.483,95%CI:0.249～0.939)and other occupations(OR=0.276,95%CI:0.090～0.850).Conclusion A part of patients with moderate-to-severe acne may experience psychological health problems.Patients with female gender,higher acne grades,longer disease duration,preference for greasy or spicy foods and lower scores in all Acne-QoL factors have a higher risk of experiencing psychological health problems.