Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with high morbidity and mortality. Circulating histones (CHs), a group of damage-associated molecular pattern molecules mainly derived from neutrophil extracellular traps, play a crucial role in sepsis by mediating inflammation response, organ injury and death through Toll-like receptors or inflammasome pathways. Herein, we first elucidate the molecular mechanisms of histone-induced inflammation amplification, endothelium injury and cascade coagulation activation, and discuss the close correlation between elevated level of CHs and disease severity as well as mortality in patients with sepsis. Furthermore, current state-of-the-art on anti-histone therapy with antibodies, histone-binding proteins (namely recombinant thrombomodulin and activated protein C), and heparin is summarized to propose promising approaches for sepsis treatment.

Sepsis-associated acute kidney injury (S-AKI) is a common complication in hospitalized and critically ill patients, which increases the risk of multiple comorbidities and is associated with extremely high mortality. Maresin 1 (MaR1), a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid has been reported to protect against inflammation and promote the regression of acute inflammation. This study proposed to systematically investigate the renoprotective effects and potential molecular mechanism of MaR1 in septic acute kidney injury. We established a S-AKI animal model by a single intraperitoneal injection of lipopolysaccharide (LPS), 10 mg/kg, on male C57BL/6J mice. LPS-stimulated (100 μg/ml) mouse kidney tubular epithelium cells (TCMK-1) were used to simulate septic AKI in vitro. The results showed that pretreatment with MaR1 significantly reduced serum creatinine and blood urea nitrogen levels as well as tubular damage scores and injury marker neutrophil gelatinase-associated lipocalin in septic AKI mice. Meanwhile, MaR1 administration obviously diminished pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1), downregulated BAX and cleaved caspase-3 expression, and upregulated BCL-2 expression in the injured kidney tissues and TCMK-1 cells. In addition, MaR1 reduced malondialdehyde production and improved the superoxide dismutase activity of renal tissues while inhibiting reactive oxygen species (ROS) production and protecting the mitochondria. Mechanistically, LPS stimulated the expression of the NOX4/ROS/NF-κB p65 signaling pathway in S-AKI kidneys, while MaR1 effectively suppressed the activation of the corresponding pathway. In conclusion, MaR1 attenuated kidney inflammation, apoptosis, oxidative stress, and mitochondrial dysfunction to protect against LPS-induced septic AKI via inhibiting the NOX4/ROS/NF-κB p65 signaling pathway.

Kidney failure is associated with high morbidity and mortality. Hemodialysis, the most prevalent modality of renal replacement therapy, uses the principle of semipermeable membranes to remove solutes and water in the plasma of patients with kidney failure. With the evolution of hemodialysis technology over the last half century, the clearance of small water-soluble molecules in such patients is adequate. However, middle molecules uremic toxins are still retained in the plasma and cause cardiovascular events, anemia, and malnutrition, which significantly contribute to poor quality of life and high mortality in maintenance hemodialysis patients. A new class of membrane, defined as a medium cut-off (MCO) membrane, has emerged in recent years. Expanded hemodialysis with MCO membranes is now recognized as the artificial kidney model closest to natural kidney physiology. This review summarizes the unique morphological characteristics and internal filtration–backfiltration mechanism of MCO membranes, and describes their effects on removing uremic toxins, alleviating inflammation and cardiovascular risk, and improving quality of life in maintenance hemodialysis patients.

AimsThis study aimed to assess the relationship between dietary inflammatory index (DII) and sex hormones in male children and adolescents aged 6-19 years.MethodsWe obtained data from the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Male participants aged 6-19 years old with the complete data of DII and sex hormones were included. Weighted multiple regression analysis and subgroup analysis were preformed to estimate the independent relationship between DII and sex hormones.ResultsA total of 1717 male participants with the average age of 13.02 ± 3.82 years were enrolled, of whom 41.3% (n=713) were children and 58.47% (n=1004) were adolescents. In children, mean DII was 0.18 ± 1.67, with scores ranging from -4.53 to 4.08. As for adolescents, the mean DII was 0.36 ± 1.98, mean total testosterone (TT) was 376.94 ± 206.69 ng/dl overall. A negative association between DII with TT and estradiol (E2) was observed (TT: β=-11.97, P=0.0006; E2: β=-0.45, P=0.0108) in male adolescent. Subgroup analysis and interaction test results indicated that this association was similar in male adolescents with different body mass index. No statistically significant association was observed in children.ConclusionsPro-inflammatory diet was associated with lower TT and E2 level in male adolescent, while no association with statistical significance between them was observed in male children. However, more studies are still needed to validate the causal relationship between DII and sex hormones.

Vascular calcification (VC) is the abnormal deposition of calcium, phosphorus, and other minerals in the vessel wall and can be commonly observed in diabetes, chronic kidney disease, and chronic inflammatory disease. It is closely associated with mortality from cardiovascular events. Traditionally, calcification is considered as a degenerative disease associated with the aging process, while increasing evidence has shown that the occurrence and development of calcification is an active biological process, which is highly regulated by multiple factors. The molecular mechanisms of VC have not yet been fully elucidated. Exosomes, as important transporters of substance transport and intercellular communication, have been shown to participate in VC. The regulation of VC by exosomes involves a number of complex biological processes, which occur through a variety of interaction mechanisms. However, the specific role and mechanism of exosomes in the process of VC are still not fully understood and require further study. This review will briefly describe the roles of exosomes in the process of VC including in the promotion of extracellular mineral deposits, induction of phenotypic conversion of vascular smooth muscle cells (VSMCs), transport of microRNA between cells, and regulation on autophagy and oxidative stress, with the aim of providing novel ideas for the clinical diagnosis and treatment of VC.

Aims: We aimed to assess the association between dietary inflammation index (DII) and abdominal aortic calcification (AAC) in US adults aged ≥40 years.Methods: Data were obtained from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). Participants who were <40 years old and missing the data of DII and AAC were excluded. DII was calculated based on a 24-h dietary recall interview for each participant. AAC score was quantified by assessing lateral spine images and severe AAC was defined as AAC score >6. Weighted multivariable regression analysis and subgroup analysis were preformed to estimate the independent relationship between DII with AAC score and severe AAC.Results: A total of 2,897 participants were included with the mean DII of −0.17 ± 2.80 and the mean AAC score of 1.462 ± 3.290. The prevalence of severe AAC was 7.68% overall, and participants in higher DII quartile tended to have higher rates of severe AAC (Quartile 1: 5.03%, Quartile 2: 7.44%, Quartile 3: 8.38%, Quartile 4: 10.46%, p = 0.0016). A positive association between DII and AAC score was observed (β = 0.055, 95% CI: 0.010, 0.101, p = 0.01649), and higher DII was associated with an increased risk of severe AAC (OR = 1.067, 95% CI: 1.004, 1.134, p = 0.03746). Subgroup analysis indicated that this positive association between DII and AAC was similar in population with differences in gender, age, BMI, hypertension status, and diabetes status and could be appropriate for different population settings.Conclusion: Higher pro-inflammatory diet was associated with higher AAC score and increased risk of severe AAC. Anti-inflammatory dietary management maybe beneficial to reduce the risk of AAC.

Background: Anticoagulation is generally used in hospitalized patients with coronavirus disease 2019 (COVID-19) as thromboprophylaxis. However, results from different studies comparing the effect of anticoagulation on the mortality of COVID-19 patients with non-anticoagulation are inconclusive.Methods: Our systematic review included observational trials if they studied anticoagulant therapy in hospitalized patients with COVID-19 for mortality or bleeding events. Dichotomous variables from individual studies were pooled by risk ratio (RR) and their 95% confidence interval (95% CI) using the random-effects model. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of evidence.Results: A total of 11 observational studies enrolling 20,748 hospitalized COVID-19 patients overall were included. A pooled meta-analysis of these studies showed that anticoagulation therapy, compared with non-anticoagulation therapy, was associated with lower mortality risk (RR 0.70, 95% CI 0.52–0.93, p = 0.01). The evidence of benefit was stronger among critically ill COVID-19 patients in the intensive care units (RR 0.59, 95% CI 0.43–0.83, p = 0.002). Additionally, severe bleeding events were not associated with the administration of anticoagulants (RR 0.93, 95% CI 0.71–1.23, p = 0.63).Conclusion: Among patients with COVID-19 admitted to hospital, the administration of anticoagulants was associated with a decreased mortality without increasing the incidence of bleeding events.

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