Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells. They are pivotal in regulating blood flow, enhancing vascular stability, and maintaining the integrity of the blood-retina barrier/blood-brain barrier. The pluripotency of pericytes allows them to differentiate into various cell types, highlighting their significance in vascular disease pathogenesis, as demonstrated by previous studies. This capability enables pericytes to be a potential biomarker for the diagnosis and a target for the treatment of vascular disorders. The retina, an essential part of the eyeball, is an extension of cerebral tissue with a transparent refractive medium. It offers a unique window for assessing systemic microvascular lesions. Routine fundus examination is necessary for patients with diabetes and hypertension. Manifestations, such as retinal artery tortuosity, dilation, stenosis, and abnormal arteriovenous anastomosis, serve as typical hallmarks of retinal vasculopathy. Therefore, studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.

Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of both the innate and adaptive immune systems, leading to an attack on healthy tissues of the body. During the development of SLE, pathogenic features, such as the formation of autoantibodies against self-nuclear antigens, cause tissue damage including necrosis and fibrosis, with increased expression levels of the type Ⅰ interferon-regulated genes. Standard treatments for lupus with immunosuppressants and glucocorticoids are not effective enough but cause side effects. As an alternative, more effective immunotherapies have been developed, including monoclonal and bispecific antibodies that target B cells, T cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Encouraging results have been observed in clinical trials with some of these therapies. Furthermore, a chimeric antigen receptor T cell therapy has emerged as the most effective, safe, and promising treatment option for SLE, as demonstrated by successful pilot studies. Additionally, some emerging evidence suggests that gut microbiota dysbiosis may significantly contribute to the severity of SLE, and the normalization of the gut microbiota through methods such as fecal microbiota transplantation presents new opportunities for effective treatment of SLE.

Parasitic helminths, taxonomically comprising trematodes, cestodes, and nematodes, are multicellular invertebrates widely disseminated in nature and have afflicted humans continuously for a long time. Helminths play potent roles in the host by generating a variety of novel molecules, including some excretory/secretory products and others that are involved in intracellular material exchange and information transfer as well as the initiation or stimulation of immune and metabolic activation. The helminth-derived molecules have developed powerful and diverse immunosuppressive effects to achieve immune evasion for parasite survival and establish chronic infections. However, they also improve autoimmune and allergic inflammatory responses and promote metabolic homeostasis by promoting metabolic reprogramming of various immune functions, and then inducing alternatively activated macrophages, T helper 2 cells, and regulatory T cell-mediated immune responses. Therefore, a deeper exploration of the immunopathogenic mechanism and immune regulatory mechanisms of helminth-derived molecules exerted in the host is crucial for understanding host-helminth interactions, as well as the development of therapeutic drugs for infectious or non-infectious diseases. In this review, we focus on the properties of helminth-derived molecules to give an overview of the most recent scientific knowledge about their pathogenic and pharmacopeial roles in immune-metabolic homeostasis.

Acute lung injury (ALI) linked to sepsis has a high mortality rate, with limited treatment options available. In recent studies, medical ozone has shown the potential to alleviate inflammation and infection. Here, we aimed to evaluate therapeutic potential of medical ozone in a mouse model of the sepsis-induced ALI by measuring behavioral assessments, lung function, and blood flow. Protein levels were quantified by Western blotting. In vitro, we performed experiments on bone marrow-derived macrophages (BMDMs) to investigate the effect of adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitors and agonists on their phagocytic activity. The results showed that medical ozone significantly improved the survival rate, ameliorated lung injury, and enhanced lung function and limb microcirculation in mice with ALI. Notably, medical ozone inhibited the formation of neutrophil extracellular traps (NETs), a crucial factor in the ALI development. Additionally, medical ozone counteracted the elevated levels of tissue factor, matrix metalloproteinase-9, and interleukin-1β. In the ALI mice, the effects of ozone were abolished, and BMDMs showed an impaired capacity to engulf NETs following the Sr-a1 knockout. Under normal physiological conditions, the administration of an AMPK antagonist showed similar effects on the Sr-a1 knockout, significantly inhibiting the phagocytosis of NETs by BMDMs. In contrast, AMPK agonists enhanced this phagocytic process. In conclusion, medical ozone may alleviate the sepsis-induced lung injury through the AMPK/SR-A1 pathway, thereby enhancing the phagocytosis of NETs by macrophages.

The intestinal mucosal barrier serves as a vital guardian of the gut health, maintaining a delicate equilibrium between gut microbiota and host immune homeostasis. Gasdermin D (GSDMD), a key executioner of pyroptosis downstream of the inflammasome, has been found to play intricate roles in modulating colitis by influencing intestinal macrophages and regulating mucus secretion from goblet cells. However, the exact nature of the regulatory function of GSDMD in maintaining intestinal immune homeostasis and defending against pathogens remains to be elucidated. In the current study, by using the Citrobacter rodentium infection model, we found that GSDMD played a key role in the defense against intestinal Citrobacter rodentium infection, with high expression levels in intestinal epithelial and lamina propria myeloid cells. Our results showed that GSDMD acted specifically in intestinal epithelial cells to combat the infection, independently of its effects on antimicrobial peptides or mucin secretion. Instead, the resistance was mediated by the N-terminal fragment of GSDMD, highlighting its importance in intestinal immunity. However, the specific mechanism underlying the N-terminal activity of GSDMD in protecting against intestinal bacterial infections requires future investigation.

The current study used multivariable logistic regression analysis to investigate associations between the intake frequencies of 13 food groups (or four diet groups) and infectious diseases. The analysis included 487849 participants from the UK Biobank, with 75209 participants diagnosed with infectious diseases. Participants reporting the highest intake frequency of processed meat (odds ratio [OR] = 1.0964, 95% confidence interval [CI]: 1.0622-1.1318) and red meat (OR = 1.0895, 95% CI: 1.0563-1.1239) had a higher risk of infectious diseases, compared with those with the lowest intake frequency. Consuming fish 2.0-2.9 times (OR = 0.8221, 95% CI: 0.7955-0.8496), cheese ≥ 5.0 times (OR = 0.882 2, 95% CI: 0.855 9-0.9092), fruit 3.0-3.9 servings (OR = 0.8867, 95% CI: 0.8661-0.9078), and vegetables 2.0-2.9 servings (OR = 0.9372, 95% CI: 0.9189-0.9559) per week were associated with a lower risk of infection. Low meat-eaters (OR = 0.9404, 95% CI: 0.9243-0.9567), fish-eaters (OR = 0.8391, 95% CI: 0.7887-0.8919), and vegetarians (OR = 0.9154, 95% CI: 0.8561-0.9778) had a lower risk of infectious diseases, compared with regular meat-eaters. The mediation analysis revealed that glycosylated hemoglobin, white blood cell count, and body mass index served as the mediators in the associations between diet and infectious diseases. The current study indicates that the intake frequency of food groups is a risk factor for infectious diseases, and fish-eaters have a lower risk of infection.

Studies have shown that differentiated embryo-chondrocyte expressed gene 1 (DEC1) promotes osteoblast osteogenesis. To investigate the role of DEC1 in postmenopausal osteoporosis, we used the two genotypes of mice (Dec1^+/+ and Dec1^−/−) to establish an ovariectomy model and found that the bone loss was significantly lower in Dec1^−/− ovariectomy mice than in Dec1^+/+ ovariectomy mice. The expression levels of RUNX2 and OSX were significantly increased in Dec1^−/− ovariectomy mice, compared with Dec1^+/+ ovariectomy mice; however, the expression levels of NFATc1, c-Fos, CTSK, and RANKL/OPG ratio were significantly decreased in Dec1^−/− ovariectomy mice, compared with those in Dec1^+/+ ovariectomy mice. Likewise, DEC1 deficiency also suppressed the expression levels of IL-6 and IL-1β. Further results showed that the mRNA expression levels of Runx2, Osx, and Alp were significantly increased in bone marrow mesenchymal stem cells of Dec1^−/− ovariectomy mice, compared with those of Dec1^+/+ ovariectomy mice. Moreover, the mRNA levels of Il1b, Il6, Tnfa, and Ifng were significantly increased in bone marrow-derived macrophages (BMMs) of Dec1^+/+ovariectomy mice, compared with those of Dec1^+/+ sham mice, but not in Dec1^−/− ovariectomy BMMs, when compared with those in Dec1^−/− sham BMMs. Additionally, the expression levels of p-IκBα and p-P65 were significantly increased in Dec1^+/+ ovariectomy BMMs, compared with those in Dec1^+/+ sham BMMs, but did not increase in Dec1^−/− ovariectomy BMMs, compared with those in Dec1^−/− sham BMMs. Taken together, DEC1 deficiency inhibited the NF-κB pathway induced by ovariectomy, thereby decreasing cytokines and subsequently inhibiting the decrease of osteogenesis and the increase of osteoclastogenesis caused by ovariectomy. The findings may provide a novel understanding of postmenopausal osteoporosis development, and offer potential avenues for the disease intervention.

Epidemiological data are scarce regarding the association of exposure to mixtures of per- and polyfluoroalkyl substances (PFASs) with liver injury in the general population. In the current study, therefore, we examined data from the National Health and Nutrition Examination Survey (2009-2018). The PFAS exposure levels were defined by the serum concentrations of PFASs with over 70% detection in samples, namely perfluorooctanoic acid, perfluorononanoic acid, perfluorohexane sulfonic acid, perfluorodecanoic acid, and perfluorooctane sulfonic acid (PFOS). We evaluated liver injury from two aspects: first, the degree of liver inflammation was determined based on levels of the serum alanine aminotransferase, aspartate aminotransferase, glutamyltransferase, and total bilirubin; second, the degree of liver fibrosis was determined based on the fibrosis-4 index. We assessed the associations of individual or total PFAS exposure with these liver injury outcomes using multivariable linear and logistic regression models, restricted cubic splines, and weighted quantile sum regression. Among the samples of 7484 American adults, the median concentration of PFOS was the highest, followed by perfluorooctanoic acid and perfluorohexane sulfonic acid. Using multivariable linear regression, we observed positive correlations between all PFAS exposure and liver enzyme levels, such as alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Additionally, the weighted quantile sum model indicated an overall positive association between exposure to the five PFASs and liver injury risk. For liver function biomarkers and liver fibrosis, perfluorononanoic acid and PFOS were the most heavily weighted chemicals, respectively. Our findings provide new epidemiological evidence indicating potential associations between PFAS exposure and adverse effects on liver injury biomarkers, highlighting the potentially harmful effects of PFAS exposure on human liver health.