Sepsis-associated encephalopathy (SAE) is a cognitive impairment associated with sepsis that occurs in the absence of direct infection in the central nervous system or structural brain damage. Microglia are thought to be macrophages of the central nervous system, devouring bits of neuronal cells and dead cells in the brain. They are activated in various ways, and microglia-mediated neuroinflammation is characteristic of central nervous system diseases, including SAE. Here, we systematically described the pathogenesis of SAE and demonstrated that microglia are closely related to the occurrence and development of SAE. Furthermore, we comprehensively discussed the function and phenotype of microglia and summarized their activation mechanism and role in SAE pathogenesis. Finally, this review summarizes recent studies on treating cognitive impairment in SAE by blocking microglial activation and toxic factors produced after activation. We suggest that targeting microglial activation may be a putative treatment for SAE.

Background: The global population of older individuals is growing, and ageing is a key risk factor for atherosclerotic cardiovascular diseases. Abnormal accumulation of senescent cells can cause potentially deleterious effects on the organism with age. As a vital marker of cellular senescence, the senescence-associated secretory phenotype (SASP) is a novel mechanism to link cellular senescence with atherosclerosis. Main body: In this review, we concretely describe the characteristics of the SASP and its regulation mechanisms. Importantly, we provide novel perspectives on how the SASP can promote atherosclerosis. The SASP from different types of senescent cells have vital roles in atherosclerosis progression. As a significant mediator of the harmful effects of senescent cells, it can play a pro-atherogenic role by producing inflammation and immune dysfunction. Furthermore, the SASP can deliver senescence signals to the surrounding vascular cells, gradually contributing to the development of atherosclerosis. Finally, we focus on a variety of novel therapeutic strategies aimed to reduce the burden of atherosclerosis in elderly individuals by targeting senescent cells and inhibiting the regulatory mechanisms of the SASP. Conclusion: This review systematically summarizes the multiple roles of the SASP in atherosclerosis and can contribute to the exploration of new therapeutic opportunities.

The C-reactive protein-triglyceride-glucose index (CTI) has emerged as an innovative composite marker for evaluating metabolic-inflammatory dysregulation, integrating markers of insulin resistance and systemic inflammation. However, the association between CTI and cardiovascular disease (CVD) or its mortality has rarely been studied. This study sought to examine CTI's associations with CVD mortality, CVD incidence, and all-cause mortality. This study included 8,679 adults from the National Health and Nutrition Examination Survey (NHANES) 2001–2010, 2015–2018. The CTI was derived as: 0.412* Ln (CRP [mg/L]) + Ln (TG [mg/dl] × FPG [mg/dl])/2, with participants categorized into quartiles. We employed Kaplan–Meier curves, cox proportional hazards model, logistic regression analyses, and restricted cubic spline (RCS) to evaluate CTI's associations with CVD mortality, total CVD incidence, and all-cause mortality across sex-stratified, age-specific, and glycemic subgroups. In this study, CTI was significantly and positively associated with CVD mortality, total CVD incidence, and all-cause mortality. CTI significantly predicted both CVD mortality (HR 2.28 [1.69–3.24]) and all-cause mortality (HR 2.14 [1.76–2.55]). Additionally, the CTI index correlated with the risk of total CVD (OR 2.85, 95% CI 2.32–3.52), congestive heart failure (OR 3.66, 95% CI 2.46–5.35), coronary heart disease (OR 2.82, 95% CI 1.95–3.97), angina pectoris (OR 2.85, 95% CI 1.89–4.22), heart attack (OR 2.59, 95% CI 1.89–3.52), and stroke (OR 2.86, 95% CI 2.00–3.85). Specifically, the association was similar between male and female, and similar in young participants and elderly participants. In different glycemic status, high levels of CTI were found to be linked to an increased risk of CVD in individuals without diabetes mellitus (DM). However, this association was not observed in individuals with DM. Our analysis revealed that elevated CTI levels were significantly associated with CVD incidence and mortality. CTI may emerge as a unique predictive marker for CVD risk.

Background: The impact of integrated lifestyles on health has attracted a lot of attention. It remains unclear whether adherence to low-risk healthy lifestyle factors is protective in individuals with metabolic syndrome and metabolic syndrome-like characteristics. We aimed to explore whether and to what extent overall lifestyle scores mitigate the risk of all-cause mortality in individuals with metabolic syndrome and metabolic syndrome-like characteristics. Methods: In total, 6934 participants from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) were included. The weighted healthy lifestyle score was constructed based on smoking, alcohol consumption, physical activity, diet, sleep duration, and sedentary behavior information. Generalized linear regression models and restricted cubic splines were used to analyze the association between healthy lifestyle scores and all-cause mortality. ​ Results: Compared to participants with relatively low healthy lifestyle scores, the risk ratio (RR) in the middle healthy lifestyle score group was 0.51 (RR = 0.51, 95% CI 0.30–0.88), and the high score group was 0.26 (RR = 0.26, 95% CI 0.15–0.48) in the population with metabolic syndrome. The difference in gender persists. In females, the RRs of the middle and high score groups were 0.47 (RR = 0.47, 95% CI 0.23–0.96) and 0.21 (RR = 0.21, 95% CI 0.09–0.46), respectively. In males, by contrast, the protective effect of a healthy lifestyle was more pronounced in the high score group (RR = 0.33, 95% CI 0.13–0.83) and in females, the protective effects were found to be more likely. The protective effect of a healthy lifestyle on mortality was more pronounced in those aged < 65 years. Higher lifestyle scores were associated with more prominent protective effects, regardless of the presence of one metabolic syndrome factor or a combination of several factors in 15 groups. What's more, the protective effect of an emerging healthy lifestyle was more pronounced than that of a conventional lifestyle. Conclusions: Adherence to an emerging healthy lifestyle can reduce the risk of all-cause mortality in people with metabolic syndrome and metabolic syndrome-like characteristics; the higher the score, the more obvious the protective effect. Our study highlights lifestyle modification as a highly effective nonpharmacological approach that deserves further generalization.

NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation contributes to the progression of atherosclerosis, and autophagy inhibits inflammasome activation by targeting macrophages. We investigated whether fucoidan, a marine sulfated polysaccharide derived from brown seaweeds, could reduce NLRP3 inflammasome activation by enhancing sequestosome 1 (p62/SQSTM1)-dependent selective autophagy to alleviate atherosclerosis in high-fat-fed ApoE-/- mice with partial carotid ligation and differentiated THP-1 cells incubated with oxidized low-density lipoprotein (oxLDL). Fucoidan significantly ameliorated lipid accumulation, attenuated progression of carotid atherosclerotic plaques, deregulated the expression of NLRP3 inflammasome, autophagy receptor p62, and upregulated microtubule-associated protein light chain 3 (LC3)-II/I levels. Transmission electron microscopy and GFP-RFP-LC3 lentivirus transfection further demonstrated that fucoidan could activate autophagy. Mechanistically, fucoidan remarkably inhibited NLRP3 inflammasome activation, which was mostly dependent on autophagy. The inhibitory effects of fucoidan on NLRP3 inflammasome were enhanced by autophagy activator rapamycin (Rapa) and alleviated by autophagy inhibitor 3-methyladenine (3-MA). Fucoidan promoted the colocalization of NLRP3 and p62. Knockdown of p62 and ATG5 by small interfering RNA significantly reduced the inhibitory effects of fucoidan treatment on NLRP3 inflammasome. The data suggest that fucoidan can inhibit NLRP3 inflammasome activation by enhancing p62/SQSTM1-dependent selective autophagy to alleviate atherosclerosis.

Aging is widespread worldwide and a significant risk factor for cardiovascular disease (CVD). Mechanisms underlying aging have attracted considerable attention in recent years. Remarkably, aging and CVD overlap in numerous ways, with deregulated nutrient sensing as a common mechanism and lifestyle as a communal modifier. Interestingly, lifestyle triggers or suppresses multiple nutrient-related signaling pathways. In this review, we first present the composition of the nutrient-sensing network (NSN) and its metabolic impact on aging and CVD. Secondly, we review how risk factors closely associated with CVD, including adverse life states such as sedentary behavior, sleep disorders, high-fat diet, and psychosocial stress, contribute to aging and CVD, with a focus on the bridging role of the NSN. Finally, we focus on the positive effects of beneficial dietary interventions, specifically dietary restriction and the Mediterranean diet, on the regulation of nutrient metabolism and the delayed effects of aging and CVD that depend on the balance of the NSN. In summary, we expound on the interaction between lifestyle, NSN, aging, and CVD.