As a grave and highly lethal clinical challenge, sepsis, along with its consequent multiorgan dysfunction, affects millions of people worldwide. Sepsis is a complex syndrome caused by a dysregulated host response to infection, leading to fatal organ dysfunction. An increasing body of evidence suggests that the pathogenesis of sepsis is both intricate and rapid and involves various cellular responses and signal transductions mediated by post-translational modifications (PTMs). Hence, a comprehensive understanding of the mechanisms and functions of PTMs within regulatory networks is imperative for understanding the pathological processes, diagnosis, progression, and treatment of sepsis. In this review, we provide an exhaustive and comprehensive summary of the relationship between PTMs and sepsis-induced organ dysfunction. Furthermore, we explored the potential applications of PTMs in the treatment of sepsis, offering a forward-looking perspective on the understanding of infectious diseases.

The COVID-19 pandemic, which is caused by the SARS-CoV-2 virus, has resulted in extensive health challenges globally. While SARS-CoV-2 primarily targets the respiratory system, clinical studies have revealed that it could also affect multiple organs, including the heart, kidneys, liver, and brain, leading to severe complications. To unravel the intricate molecular interactions between the virus and host tissues, we performed an integrated transcriptomic analysis to investigate the effects of SARS-CoV-2 on various organs, with a particular focus on the relationship between renal failure and COVID-19. A comparative analysis showed that SARS-CoV-2 triggers a systemic immune response in the brain, heart, and kidney tissues, characterized by significant upregulation of cytokine and chemokine secretion, along with enhanced migration of lymphocytes and leukocytes. A weighted gene co-expression network analysis demonstrated that SARS-CoV-2 could also induce tissue-specific transcriptional profiling. More importantly, single-cell sequencing revealed that COVID-19 patients with renal failure exhibited lower metabolic activity in lung epithelial and B cells, with reduced ligand-receptor interactions, especially CD226 and ICAM, suggesting a compromised immune response. A trajectory analysis revealed that COVID-19 patients with renal failure exhibited less mature alveolar type 1 cells. Furthermore, these patients showed potential fibrosis in the hearts, liver, and lung increased extracellular matrix remodeling activities. However, there was no significant metabolic dysregulation in the liver of COVID-19 patients with renal failure. Candidate drugs prediction by Drug Signatures database and LINCS L1000 Antibody Perturbations Database underscored the importance of considering multi-organ effects in COVID-19 management and highlight potential therapeutic strategies, including targeting viral entry and replication, controlling tissue fibrosis, and alleviating inflammation.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis causes a high mortality rate and current treatment focuses on supportive therapies but lacks specific therapeutic targets. Notably, sirtuins (SIRTs) shows potential clinical application in the treatment of sepsis. It has been demonstrated that SIRTs, the nicotinamide adenine dinucleotide+(NAD+)-dependent deacetylases that regulate key signaling pathways in eukaryotes and prokaryotes, are involved in a variety of biological processes. To date, seven mammalian yeast Sir2 homologs have been identified. SIRTs can regulate inflammation, oxidative stress, apoptosis, autophagy, and other pathways that play important roles in sepsis-induced organ dysfunction. However, the existing studies on SIRTs in sepsis are too scattered, and there is no relevant literature to integrate them. This review innovatively summarizes the different mechanisms of SIRTs in sepsis organ dysfunction according to the different systems, and focuses on SIRT agonists, inhibitors, and targeted drugs that have been proved to be effective in the treatment of sepsis, so as to integrate the clinical research and basic research closely. We searched PubMed for all literature related to SIRTs and sepsis since its inception using the following medical subject headings: sirtuins, SIRTs, and sepsis. Data on the mechanisms of SIRTs in sepsis-induced organ damage and their potential as targets for disease treatment were extracted.

Systemic inflammation generally coexists with functional limitations that seriously affect quality of life. This study aimed to investigate the association between systemic inflammation in midlife and the risk of functional limitations in late-life. A total of 10,044 participants with an average age of 53.9 ± 5.7 years at baseline were included in a cohort study. At the last follow-up, the prevalence of impaired activities of daily living (ADLs), instrumental activities of daily living (IADLs), and lower extremity function (LEF) was 14.7%, 21.6%, and 50.3%, respectively. The values of four inflammatory biomarkers were used to calculate the inflammation composite score. Compared with the participants in the lowest quartile of the inflammation composite score (Q1), those in the highest quartile (Q4) exhibited an odds ratio (OR) of 1.589 and a 95% confidence interval (CI) of 1.335-1.892 for impaired ADLs, an OR of 1.426 and a 95% CI of 1.228-1.657 for impaired IADLs, and an OR of 1.728 and a 95% CI of 1.526-1.957 for impaired LEF. The association between systemic inflammation and functional limitations was partly mediated by cardiac and brain function. The present study provides evidence that systemic inflammation in midlife is associated with a higher risk of late-life functional limitations. Protecting vital organ functions in midlife may have a positive impact on reducing the risk of future functional limitations.Trial registration: www.clinicaltrials.gov ; Unique identifier: NCT00005131.

OBJECTIVE: Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients.
METHODS: This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models.
RESULTS: Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p < 0.001). Logistic regression analysis showed that CatB, S100-A9, VCAM-1, prosaposin, and NGAL could be used for preoperative diagnosis and postoperative prediction of organ dysfunction. CatB and S100-A9 were possible predictive factors for preoperative diagnosis of renal failure in septic patients. Internal validation was assessed using the bootstrapping validation. The preoperative diagnosis of renal failure model displayed good discrimination with a C-index of 0.898 (95% confidence interval 0.843-0.954) and good calibration.
CONCLUSIONS: Serum CatB, S100-A9, VCAM-1, prosaposin, and NGAL may be novel markers for preoperative diagnosis and postoperative prediction of organ dysfunction. Specifically, S100-A9 and CatB were indicators of preoperative renal dysfunction in septic patients. Combining these two biomarkers may improve the accuracy of predicting preoperative septic renal dysfunction.
BACKGROUND: The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200060418) on June 1, 2022.

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (β -0.36, 95% CI -0.59 to 0.13) and activated partial thromboplastin time (APTT) (β -1.08, 95% CI -1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (β -2085.48, 95% CI -3892.35 to 278.61) in univariate analysis, and with the PT (β -0.36, 95% CI -0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (β -0.57, 95% CI -0.95 to 0.19), mechanical ventilation time (β -23.11, 95% CI -36.54 to 9.69), and length of ICU stay (β -1.28, 95% CI -2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research.

Sepsis, a complex clinical syndrome characterized by an exaggerated host response to infection, often necessitates hospitalization and intensive care unit admission. Delayed or inaccurate diagnosis of sepsis, coupled with suboptimal treatment strategies, can result in unfavorable outcomes, including mortality. Maresins, a newly discovered family of lipid mediators synthesized from docosahexaenoic acid by macrophages, have emerged as key players in promoting inflammation resolution and the termination of inflammatory processes. Extensive evidence has unequivocally demonstrated the beneficial effects of maresins in modulating the inflammatory response associated with sepsis; however, their bioactivity and functions exhibit remarkable diversity and complexity. This article presents a comprehensive review of recent research on the role of maresins in sepsis, aiming to enhance our understanding of their effectiveness and elucidate the specific mechanisms underlying their actions in sepsis treatment. Furthermore, emerging insights into the management of patients with sepsis are also highlighted.

Apelin is the native ligand for the G protein-coupled receptor APJ. Numerous studies have demonstrated that the Apelin/APJ system has positive inotropic, anti-inflammatory, and anti-apoptotic effects and regulates fluid homeostasis. The Apelin/APJ system has been demonstrated to play a protective role in sepsis and may serve as a promising therapeutic target for the treatment of sepsis. Better understanding of the mechanisms of the effects of the Apelin/APJ system will aid in the development of novel drugs for the treatment of sepsis. In this review, we provide a brief overview of the physiological role of the Apelin/APJ system and its role in sepsis.

As an uncontrolled inflammatory response to infection, sepsis and sepsis induced organ dysfunction are great threats to the lives of septic patients. Unfortunately, the pathogenesis of sepsis is complex and multifactorial, which still needs to be elucidated. Pyroptosis is a newly discovered atypical form of inflammatory programmed cell death, which depends on the Caspase-1 dependent classical pathway or the non-classical Caspase-11 (mouse) or Caspase-4/5 (human) dependent pathway. Many studies have shown that pyroptosis is related to sepsis. The Gasdermin proteins are the key molecules in the membrane pores formation in pyroptosis. After cut by inflammatory caspase, the Gasdermin N-terminal fragments with perforation activity are released to cause pyroptosis. Pyroptosis is closely related to the occurrence and development of sepsis induced organ dysfunction. In this review, we summarized the molecular mechanism of pyroptosis, the key role of pyroptosis in sepsis and sepsis induced organ dysfunction, with the aim to bring new diagnostic biomarkers and potential therapeutic targets to improve sepsis clinical treatments.

Sepsis is a major disease that threatens human life and health. Clinically, it is mainly based on supportive treatment and lacks specific treatment methods. Acupuncture has important clinical significance in the prevention and treatment of sepsis. In the present paper, we systematically searched CNKI and PubMed databases, included the clinical trials and animal experiments on the prevention and treatment of sepsis with acupuncture, summarized the clinical efficacy and the mechanism of acupuncture. Results indicate that the role of acupuncture therapies in improving sepsis involves inhibiting systemic inflammatory response, alleviating oxidative stress, regulating immune system, and resisting cell apoptosis, thus having a protective effect on multiple organs. The mechanism involves multiple signaling pathways and related factors.
脓毒症是威胁人类生命健康的重大疾病，临床多以支持治疗为主，缺乏特异性的治疗方法，而针刺防治脓毒症具有重要的临床意义。本文系统检索中国期刊全文数据库和PubMed数据库，纳入针刺防治脓毒症的临床试验和动物实验文献，归纳总结针刺的临床疗效及作用机制。针刺可通过抑制全身炎性反应、减轻氧化应激、调节免疫系统、抗细胞死亡起到多器官保护作用，其机制涉及多条信号通路、免疫细胞和细胞因子。.