Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set.

Background: Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA. Methods: AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated. Results: In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration. Conclusion: The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.

Bacillus subtilis ameliorates Escherichia coli-induced endometritis in mice via maintaining endometrial barrier and inhibiting inflammatory response.

Endometritis is a common obstetric disease that occurs most frequently after parturition in a variety of animals. Animal infertility due to endometritis severely hinders animal husbandry and often causes serious economic losses to the dairy farming industry. According to reports, Bacillus subtilis (B. subtilis) can prevent pathogenic colonization of epithelial cells and exert immunostimulatory effects. The present study aimed to reveal the protective effect of B. subtilis on endometritis induced by Escherichia coli (E. coli) in mice. The experimental model required in this experiment was established by injecting E. coli intrauterinely, and different concentrations of B. subtilis H28 were administered 10 days before E. coli injection. The pathological changes in the uterine tissue of mice were assessed by haematoxylin-eosin (H&E) staining. Myeloperoxidase (MPO) activity measurements and enzyme-linked immunosorbent assay (ELISA) based measurement of pro-inflammatory cytokines levels were performed. Activation of NF-κB signaling pathway were detected by Western blot, and the changes in the levels of tight junction proteins (TJPs) was analyzed using Western blot detection and quantitative real-time polymerase chain reaction (qRT-PCR). As seen from the results, B. subtilis H28 pretreatment decreased uterine neutrophil infiltration, IL-1ß and TNF-α production, and the NF-κB activation during endometritis induced by E. coli. In addition, B. subtilis H28 significantly increased the expression of the tight junction proteins ZO-1, claudin-3 and occludin in uterine infected with E. coli. In conclusion, in the present study, we found that B. subtilis H28 ameliorated E. coli-induced endometritis by maintaining the endometrial barrier and inhibiting the inflammatory response.

Activation of the GPX4/TLR4 Signaling Pathway Participates in the Alleviation of Selenium Yeast on Deltamethrin-Provoked Cerebrum Injury in Quails.

Deltamethrin (DLM) is a member of pyrethroid pesticide widely applied for agriculture and aquaculture, and its residue in the environment seriously threatens the bio-safety. The cerebrum might be vulnerable to pesticide-triggered oxidative stress. However, there is no specific antidote for treating DLM-triggered cerebral injury. Selenium (Se) is an essential trace element functionally forming selenoprotein glutathione peroxidase (GPX) in antioxidant defense. Se yeast (SY) is a common and effective organic form of Se supplement with high selenomethionine content. Accordingly, this study focused on investigating the therapeutic potential of SY on DLM-induced cerebral injury in quails after chronically exposing to DLM and exploring the underlying mechanisms. Quails were treated with/without SY (0.4 mg kg-1 SY added in standard diet) in the presence/absence of DLM (45 mg kg-1 body weight intragastrically) for 12 weeks. The results showed SY supplementation ameliorated DLM-induced cerebral toxicity. Concretely, SY elevated the content of Se and increased GPX4 level in DLM-treated quail cerebrum. Furthermore, SY enhanced antioxidant defense system by upregulating nuclear factor-erythroid-2-related factor 2 (Nrf2) associated members. Inversely, SY diminished the changes of apoptosis- and inflammation-associated proteins and genes including toll-like receptor 4 (TLR4). Collectively, our results suggest that dietary SY protects against DLM-induced cerebral toxicity in quails via positively regulating the GPX4/TLR4 signaling pathway. GPX4 may be a potential therapeutic target for insecticide-induced biotoxicity.

Probiotic Enterococcus mundtii H81 inhibits the NF-κB signaling pathway to ameliorate Staphylococcus aureus-induced mastitis in mice.

Mastitis is part of the aggressive diseases that affecting the development of dairy farming. Lactic acid bacteria (LAB), an important microbiological agent of gastrointestinal flora, can effectively promote the development of the immune system. Herein, the objectives of this study is to explore the protective role of LAB on Staphylococcus aureus(S. aureus)-induced mastitis in mice. 88 strains of suspected LAB were isolated from the milk of healthy dairy cows. Antibacterial activity was screened, and the 16S rRNA sequence analysis showed that the bacteria were Enterococcus mundtii H81 (E. mundtii H81). Furthermore, the model of mastitis has been established by nipple duct injection of S. aureus in mice, while E. mundtii H81 was treated 2 h before S. aureus injection. Twenty-four hours later of S. aureus infection, the mammary gland tissues were collected. The pathological changes of the mammary gland were observed by H&E staining. The levels of TNF-α and IL-1ß were measured by ELISA and the myeloperoxidase (MPO) activity was measured by the MPO assay kit. We also observed the changes of nuclear transcription factor kappa B (NF-κB) by using western blotting. The results showed that E. mundtii H81 pretreatment reduced neutrophil infiltration, and significantly reduce the secretion of TNF-α and IL-1ß, down-regulate the phosphorylation of p65 NF-κB and IκB, and the expression of tight junction protein Claudin 3 and ZO-1 was up-regulated. Collectively, our findings showed that E. mundtii H81 protects mammary gland from S. aureus-induced mastitis, which may be a candidate of treatment for mastitis infected by S. aureus.

Cognition in chronic kidney disease patients: Evaluation with the Beijing version of the Montreal Cognitive Assessment.

Patients with chronic kidney disease (CKD) may undergo cognitive impairment. We aimed to explore the cognition of patients with cognitive impairment (CI) and no cognitive impairment (NCI) respectively and the effect of demographics, estimated glomerular filtration rate (eGFR), number of comorbidities (NCD), and hemoglobin on CI in Chinese patients with CKD at stage 3-5 treated by nondialysis by using the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ). A total of 120 patients with CKD were recruited from the Department of Nephrology at the Affiliated Hospital of Nanjing University of Chinese Medicine at in-patient and out-patient follow up. A logistic regression model was performed to assess the effect of these variables on CI of CKD patients. The results indicated that the CI group was mainly in the decline of visuospatial and executive function, abstraction, and memory, compared with the NCI group. In addition, years of education, eGFR and NCD were found as predictors of CI of CKD patients at stage 3-5. Specifically, lower eGFR, less years of education and more comorbidities were risk predictors of CI.

Luteolin alleviates inorganic mercury-induced kidney injury via activation of the AMPK/mTOR autophagy pathway.

Inorganic mercury is a ubiquitous toxic pollutant in the environment. Exposure to inorganic mercury can cause various poisonous effects, including kidney injury. However, no safe and effective treatment for kidney injury caused by inorganic mercury has been found and used. Luteolin (Lut) possesses various beneficial bioactivities. Here, our research aims to investigate the protective effect of Lut on renal injury induced by mercury chloride (HgCl2) and identify the underlying autophagy regulation mechanism. Twenty-eight 6-8 weeks old Wistar rats were randomly assigned to four groups: control, HgCl2, HgCl2 + Lut, and Lut. We performed the determination of oxidative stress and renal function indicators, histopathological analysis, the terminal deoxynucleotidyl transferase-mediated deoxyuracil nucleoside triphosphate nick-end labeling assay to detect apoptosis, western blot detection of autophagy-related protein levels, and atomic absorption method to detect mercury content. Our results showed that Lut ameliorated oxidative stress, apoptosis and restored the autophagy and renal function caused by HgCl2 in rats. Concretely, the level of nuclear factor E2-related factor, renal adenosine monophosphate-activated protein kinase (AMPK) expression, and autophagy regulation-related proteins levels were down-regulated, and the mammalian target of rapamycin (mTOR) expression was up-regulated by HgCl2 treatment. However, Lut treatment reversed the above changes. Notably, Lut reduced the accumulation of HgCl2 in the kidneys and promoted the excretion of HgCl2 through urine. Collectively, our results demonstrate that Lut can attenuate inorganic mercury-induced renal injury via activating the AMPK/mTOR autophagy pathway. Therefore, Lut may be a potential biological medicine to protect against renal damage induced by HgCl2.