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Yanyan Lu,1,* Qiang Wang,2,* Xuzhen Liu,1 Shuzhan Gao,1 Sulin Ni,1 Jing Sun,1 Xijia Xu1 1Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital, Nanjing, People’s Republic of China; 2Department of Medical Psychology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xijia Xu, Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital, Nanjing, People’s Republic of China, Tel +86-13739192705, Email xuxijia@c-nbh.comPurpose: Acute and transient psychotic disorder (ATPD), a psychosis frequently diagnosed, can potentially evolve into chronic conditions like schizophrenia (SCZ) and other mental disorders. This study aimed to develop a predictive model based on clinical data to forecast the transition from ATPD to SCZ and to identify the predictive factors.Methods: According to the diagnostic criteria issued by the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), 396 inpatients diagnosed with ATPD were collected in this study. The Cox proportional-hazards regression model was performed using demographic data, clinical characteristics, and inflammatory markers to identify independent predictors for subsequent diagnostic transition (SDT) to SCZ.Results: During the follow-up period, 43.69% (n = 173) of ATPD patients had their diagnoses revised to SCZ. The multivariate Cox regression analysis identified post-treatment monocyte count, post-treatment monocyte/lymphocyte ratio (MLR), and the presence of schizophreniform symptoms as significant predictors for the diagnostic revision. Time-dependent receiver operating characteristic (TimeROC) analyses were developed. The AUC value at the 5-year follow-up was 0.728 for combined predictors, 0.702 for post-treatment monocyte count, 0.764 for post-treatment MLR, and 0.535 for the presence of schizophreniform symptoms.Conclusion: The combined predictors had good predictive ability for the diagnostic transition from acute and transient psychotic disorder to schizophrenia.Keywords: acute and transient psychotic disorder, Schizophrenia, inflammation, subsequent-diagnostic-transition, monocyte count, monocyte–lymphocyte ratio

Xiaofen Xu,1,* Wumeng Jin,1,* Jingyi Song,1 Xuanming Hu,1 Lu Lu,2 Jida Zhang,1 Changfeng Hu1 1College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jida Zhang; Changfeng Hu, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China, Email zhjd82@tom.com; zhudianzhuifeng@163.comBackground: Liver injury, such as nonalcoholic fatty liver disease, is a common symptom observed in patients with gout/hyperuricaemia. However, the exact mechanisms are still unclear. There is ongoing controversy about whether representative agents like colchicine and febuxostat, commonly used to manage gout, could also help prevent the liver injury. Liver plays a crucial role in uric acid (UA) production and lipid metabolism. Thus, the study aimed to investigate the aberrant lipid metabolism in the liver during injury and the effects of these drugs.Methods: An advanced multi-dimensional mass spectrometry-based shotgun lipidomics technology was employed for class-targeted lipid analysis of cellular lipidomes in hepatic tissue of a gouty model induced by a combination of monosodium urate crystals and high-fat diet with or without treatment with colchicine and febuxostat. Serum UA, blood urea nitrogen, creatinine, proinflammatory cytokines, expression of AMP-activated protein kinase protein, footpad histopathology, and footpad swelling and pain threshold of these mice were assessed to evaluate the progression of gout.Results: Lipidomics analysis clearly demonstrated that the ectopic fat accumulation as well as changes in fatty acyls composition in TAG pool, impaired mitochondrial function resulted by decreased tetra 18:2 cardiolipin, and reduced 4-hydroxyalkenal bioavailability in liver tissue could contribute to liver damage to the gouty model. Treatment with colchicine or febuxostat not only ameliorated gouty symptoms but also corrected these abnormal hepatic lipid metabolism patterns.Conclusion: This study shed light on underlying mechanism(s) for liver injury in gout/hyperuricaemia and suggested that administration of drugs like colchicine and febuxostat could prevent liver injury.Keywords: gout, hepatic lipidome, febuxostat, colchicine, inflammation

Jie Xu,1,2 Liujun Tao,1 Liangyan Jiang,1 Jie Lai,1 Juntao Hu,1 Zhanhong Tang1 1Department of Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Critical Care Medicine, Suining Central Hospital, Suining, Sichuan, 629000, People’s Republic of ChinaCorrespondence: Zhanhong Tang; Juntao Hu, Department of Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, Tel +86 13978816316 ; +86 18978866565, People’s Republic of China, Email tangzhanhong139@sina.com; hujuntao80@126.comPurpose: Sepsis-associated acute lung injury (SA-ALI) is a common complication in patients with sepsis, contributing to high morbidity and mortality. Excessive inflammation and oxidative stress are crucial contributors to lung injury in sepsis. This study aims to examine the protective effects of moderate hypothermia on SA-ALI and explore the underlying mechanisms.Methods: Sepsis was induced in rats through cecal ligation and puncture followed by intervention with moderate hypothermia (32– 33.9°C). Blood, bronchoalveolar lavage fluid, and lung tissues were collected 12 hours post-surgery. Inflammatory responses, oxidative injury, SA-ALI-related pathophysiological processes, and Keap1/GSK3β/Nrf2/GPX4 signaling in septic rats were observed by ELISA, lung W/D ratio, immunohistochemistry, immunofluorescence, histological staining, Western blotting, RT-qPCR, and TEM assays.Results: Moderate hypothermia treatment alleviated lung injury in septic rats, reflected in amelioration of pathological changes in lung structure and improved pulmonary function. Further, moderate hypothermia reduced arterial blood lactate production and suppressed the expression of inflammatory factors IL-1β, IL-6, and TNF-α; downregulated ROS, MDA, and redox-active iron levels; and restored GSH and SOD content. TEM results demonstrated that moderate hypothermia could mitigate ferroptosis in PMVECs within lung tissue. The underlying mechanism may involve regulation of the Keap1/Nrf2/SLC7A11/GPX4 signaling pathway, with the insulin pathway PI3K/Akt/GSK3β also playing a partial role.Conclusion: Collectively, we illustrated a novel potential therapeutic mechanism in which moderate hypothermia could alleviate ferroptosis induced by excessive inflammation and oxidative stress via the regulation of Keap1/GSK3β/Nrf2/GPX4 expression, hence ameliorating acute lung injury in sepsis.Keywords: moderate hypothermia, sepsis, acute lung injury, ferroptosis, Nrf2, inflammation

Abstract Septic lung injury is strongly associated with polarization of M1 macrophages and excessive cytokine release. Fibroblast growth factor (FGF) signaling plays a role in both processes. However, the impact of FGF2 deficiency on macrophage polarization and septic acute lung injury remains unclear. To investigate this, we obtained macrophages from FGF2 knockout mice and examined their polarization and inflammatory cytokine expression. We also eliminated endogenous macrophages using clodronate liposomes and administered FGF2 knockout or WT macrophages intravenously in conjunction with cecal ligation and puncture (CLP) surgery to induce sepsis. In vitro analysis by flow cytometry and real-time PCR analysis demonstrated that FGF2 deficiency resulted in increased expression of M1 markers (iNOS and CD86) and inflammatory cytokines (CXCL1, IL1β, and IL6), especially after LPS stimulation. Additionally, immunofluorescence demonstrated increased nuclear translocation of p65 NF-κB in FGF2 knockout macrophages and RNA-seq analysis showed enrichment of differentially expressed genes in the IL17 and TNFα inflammatory signaling pathways. Furthermore, in vivo experiments revealed that depletion of FGF2 in macrophages worsened sepsis-induced lung inflammation, lung vascular leak, and lung histological injury, accompanied by an increase in CD86-positive cells and apoptosis. Our study suggests that FGF2 deficiency in macrophages plays a critical role in the pathogenesis of septic ALI, possibly because of the enhanced M1 macrophage polarization and production of proinflammatory cytokines. These findings provide empirical evidence for potential therapeutic interventions targeting FGF2 signaling to modulate the polarization of M1 and M2 macrophages in the management of sepsis-induced acute lung injury.

Abstract Objectives The study aimed to investigate the interaction of intraoperative stress hyperglycemia with monocyte functions and their impact on major adverse events (MAEs) in acute aortic dissection (AAD) patients who underwent open repair surgery. Methods A total of 321 adults who underwent open surgery for AAD at two tertiary medical centers in China were enrolled in the study. The primary endpoint was defined as the incidence and characteristics of perioperative stress hyperglycemia. The secondary endpoints included the incidence of postoperative MAEs, postoperative monocyte counts and inflammatory cytokine expression. Multi-logistic, linear regression and receiver operating characteristic (ROC) curve analyses were used to establish relationships between intraoperative time-weighted average glucose (TWAG), day-one postoperative monocyte counts, serum inflammatory cytokines and postoperative outcomes. In addition, in vitro experiments were conducted to evaluate changes in the inflammatory features of monocytes under high glucose conditions. Results Intraoperative hyperglycemia, as indicated by a TWAG level over 142 mg/dL, was associated with elevated postoperative monocyte counts and inflammatory cytokines, which correlated with extended intensive care unit (ICU) stays and worsened outcomes. In vitro, high glucose treatment induced mitochondrial impairment in monocytes, increased the release of inflammatory cytokines and the proportion of classical monocytes from AAD patients. Conclusions Intraoperative stress hyperglycemia, in combination with day-one postoperative monocyte counts, were clinically significant for predicting adverse outcomes in AAD patients undergoing open repair surgery. Elevated glucose concentrations shaped the inflammatory features of monocytes in AAD by impairing mitochondrial functions. Graphical abstract High glucose-driven mitochondrial functional impairment mediates a more pronounced monocytic inflammatory state in Stanford type-A AAD.

Abstract Background Dietary patterns and lifestyle factors can influence the intensity of systemic inflammation and, consequently, the development and progression of coronary artery calcification (CAC). This study aimed to explore the relationship between the inflammatory potentials of diet and lifestyle, as captured by novel dietary and lifestyle inflammation scores (DIS and LIS), with CAC incidence and progression. Methods We analyzed data on 5949 Black and White men and women ≥ 45 years old participating in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Baseline data on diet and lifestyle factors were collected from 2000 to 2002 and used to construct the DIS and LIS, which reflect the overall inflammatory potential of diet and lifestyle. Cox proportional hazard regression was used to calculate the hazard ratios (HR) and 95% confidence intervals (95% CI) for CAC incidence and progression across quartiles of DIS and LIS, adjusting for potential confounders. Results Over a median follow-up of 8.0 years, among 2638 participants with zero CAC score at baseline, 977 individuals developed positive scores, and 1681 out of 2561 participants showed CAC progression. For individuals in the highest (more pro-inflammatory) compared to the lowest (more anti-inflammatory) quartiles of the LIS, the multivariable-adjusted HR for CAC incidence was 1.35 (95% CI, 1.10–1.65; P trend

Abstract Background Age-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. Recently, it has been found that there is a local Renin–angiotensin system (RAS) in human ovary and it plays a key role. Methods After collecting follicular fluid from women who received oocyte retrieval for pure male factor infertility, the level of RAS components in it were detected, and the correlation analysis by linear regression. Then, the in vivo experiments on female C57BL/6 mice were designed to measure ovarian function, and the transcription and translation levels of RAS pathway were detected by molecular biology methods. Moreover, the role of RAS in regulating inflammation and oxidative stress in the co-culture system were explored in in vitro experiments on KGN cells. Results First, a total of 139 samples of analyzable follicular fluid were obtained. The local RAS of ovary, which is independent of systemic RAS (P > 0.05), is affected by age (Pearson r 0.05). Conclusions Together, our findings indicate that a novel possible mechanism to explain how stem cells restore age-related ovarian functional decline.

Abstract Background Grilled Nux Vomica (GNV) is a promising traditional Chinese medicine to treat myasthenia gravis (MG), but its effects and mechanisms need further exploration. Methods Experimental autoimmune MG (EAMG) model was established by muscle-specific kinase (MuSK) induction on C57BL/6 J mice. Mice were treated with GNV and/or ruxolitinib (JAK2 inhibitor) or AG490 (STAT3 inhibitor) for 30 days via gavage after modeling and randomized into 7 groups: control, model, low-dose GNV, middle-dose GNV, high-dose GNV, GNV + ruxolitinib, GNV + AG490. Body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity (agrin and acetylcholine receptor [AChR] levels), inflammatory factors (IL-2 and IL-6), and the activation of the JAK2/STAT3 pathway were measured and compared between groups. Results GNV significantly improved body weight and muscle strength, as well as reduced clinical scores, MuSK levels, and inflammatory markers (IL-2 and IL-6) levels compared with untreated EAMG mice. GNV also protected the neuromuscular junction and increased agrin and AChR co-expression in a dose-dependent manner. In addition, GNV attenuated the levels of p-JAK2 and p-STAT3, which are aberrantly upregulated in EAMG mice. After co-treatment with ruxolitinib or AG490, the effect of GNV on body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity, levels of inflammatory factors, and JAK2/STAT3 pathway was further amplified in EAMG mice. Conclusions GNV improves MG by inhibiting the JAK2/STAT3 pathway, which might be an effective therapeutic strategy for MG.

Abstract The exocrine pancreas is the main source of digestive enzymes which are released from secretory vesicles of acinar cells into the small intestine. Enzymes, including amylases, proteases and lipases, degrade the ingested food and thus determine the nutritional substrate for the gut microbiota. Acute (AP) and chronic pancreatitis (CP) are associated with a transitional or progressive exocrine pancreatic dysfunction, we analysed in the present study how an experimental induction of pancreatitis in mouse models affects the colonic and duodenal microbiome composition. Evaluation by 16 S rRNA gene sequencing revealed specific microbiome changes in colonic as well as in duodenal samples in different models of AP and CP. Mild acute pancreatitis, which is associated with a transient impairment of pancreatic secretion showed only minor changes in microbial composition, comparable to the ones seen in progressive dysfunctional mouse models of CP. The strongest changes were observed in a mouse model of severe AP, which suggest a direct effect of the immune response on gut microbiome in addition to a pancreatic dysfunction. Our data indicate that highly dysbiotic microbiome changes during pancreatitis are more associated with the inflammatory reaction than with a disturbed pancreatic secretion.

Abstract Some drugs or chemicals exhibit different safety profiles in newborns/young children compared to adults. Polyhexamethyleneguanidine phosphate (PHMG-P) has been implicated in the humidifier disinfectant tragedy in 2011. There are limited reports on the toxicity of PHMG-P in neonatal animals. This study aimed to assess the toxicity of PHMG-P in neonates and to compare toxicity between young and adult mice. Mice aged 7–10 days and 8 weeks were anesthetized with isoflurane and then intranasally instilled with 0.9 mg/kg and 1.5 mg/kg PHMG-P once weekly for 4 weeks. The control group was given a corresponding volume of saline intranasally. Approximately 20 h after the 4th instillation, all mice (juveniles aged 28‒31 days and adults aged 11 weeks) were euthanized. Assessments included body weights, organ weights, cytokine production, and histopathological examinations. Both juvenile and adult mice exhibited significant pulmonary toxicity. There were no significant changes in body weight in either male or female juveniles, whereas adult mice experienced 5.0‒22.2% weight loss. However, lung weights increased in both age groups, accompanied by rises in cytokines and chemokines. Histopathological analyses revealed significant lung changes in both juvenile and adult mice, including immune cell infiltration, foamy macrophage, and granulomatous inflammation. PHMG-P is known to cause inflammation and fibrotic changes in rodents and humans that persist even during long recovery periods. Further research is required to explore the long-term health effects of PHMG-P following repeated early-life exposure.

Abstract This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p

Abstract This study aimed to examine whether or not aluminum chloride (AlCl3)-induced hepatotoxicity might be mitigated using magnetic water (MW) in rats. This study involved 28 adult male rats randomly assigned into the following 4 groups (7 rats/group): normal control (Cnt), MW, AlCl3, and Al Cl3 + MW. The Cnt group orally received normal saline, the MW group drank MW ad libitum for 2 months, and the AlCl3 and AlCl3 + MW groups were orally administered AlCl3 (40 mg/kg b.w.) alone or in combination with MW for 2 months, respectively. MW reduced AlCl3 toxicity as proved at functional, molecular, and structural levels. Functionally, MW reduced serum levels of liver enzymes (ALT, AST, ALP, GGT), while increased total proteins, and albumin. MW also restored redox balance in the liver (lower MDA levels, higher activities of CAT and SOD enzymes, and upregulated expression of NrF2, HO-1, and GST genes. Molecularly, MW downregulated hepatic expression of the epigenetic (HDAC3), inflammatory (IL1β, TNFα, NFκβ), and endoplasmic reticulum stress (XBP1, BIP, CHOP) genes. Structurally, MW enhanced liver histology. With these results, we could conclude that MW has the potential to ameliorate the hepatotoxic effects of AlCl3 through targeting oxidative stress, inflammation, epigenesis, and endoplasmic reticulum stress.

Abstract Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury.

Abstract Cardiovascular disease (CVD) is a major cause of death in the female population. The current study aimed to examine the relationship between CVD risk and novel endothelial dysfunction biomarkers [i.e., endocan, adiponectin and intercellular adhesion molecule (ICAM)-1] and carotid intima-media thickness (cIMT), respectively in a cohort of disease-free women of reproductive age. A total of 129 women were selected. Serum endocan, adiponectin and ICAM-1 were measured by a commercial enzyme-linked immunosorbent assay and cITM was determined by ultrasound. Cardiovascular risk score (CVRS) was calculated. The lowest endocan (p for trend = 0.051) and adiponectin (p for trend = 0.040) levels were found in a group of subjects with the highest CVRS. The cIMT values were the highest in second tertile subgroups, with the highest 75th percentile in a third tertile CVRS group, while the lowest cIMT values were detected in the lowest CVRS tertile group (p for trend = 0.001). A significant positive correlation between cIMT and CVRS (ρ = 0.307, p

Abstract Background Inflammation is characterized by a metabolic switch promoting glycolysis and lactate production. Hexokinases (HK) catalyze the first reaction of glycolysis and inhibition of epithelial HK2 protected from colitis in mice. HK2 expression has been described as elevated in patients with intestinal inflammation; however, there is conflicting data from few cohorts especially with severely inflamed individuals; thus, systematic studies linking disease activity with HK2 levels are needed. Methods We examined the relationship between HK2 expression and inflammation severity using bulk transcriptome data derived from the mucosa of thoroughly phenotyped inflammatory bowel disease (IBD) patients of two independent cohorts including both subtypes Crohn’s disease (CD) and ulcerative colitis (UC). Publicly available single-cell RNA sequencing data were analyzed, and immunofluorescence staining on colonic biopsies of unrelated patients with intestinal inflammation was performed to confirm the RNA-based findings on cellular and protein level. Results HK2 expression gradually increased from mild to intermediate inflammation, yet strongly declined at high inflammation scores. Expression of epithelial marker genes also declined at high inflammation scores, whereas that of candidate immune marker genes increased, indicating a cellular remodeling of the mucosa during inflammation with an infiltration of HK2-negative immune cells and a loss of terminal differentiated epithelial cells in the apical epithelium—the main site of HK2 expression. Normalizing for the enterocyte loss clearly identified epithelial HK2 expression as gradually increasing with disease activity and remaining elevated at high inflammation scores. HK2 protein expression was mostly restricted to brush border enterocytes, and these cells along with HK2 levels vanished with increasing disease severity. Conclusions Our findings clearly define dysregulated epithelial HK2 expression as an indicator of disease activity in intestinal inflammation and suggest targeted HK2-inhibition as a potential therapeutic avenue.

Abstract Background Metabolic syndrome (MetS) imposes a significant health burden on patients globally. Chronic low-grade inflammation is pivotal in the onset and progression of this condition. However, the role of the novel inflammatory marker, red cell distribution width to albumin ratio (RAR), in the development of MetS remains unclear. Methods This population-based cross-sectional study utilized data from the 2011–2020 National Health and Nutrition Examination Survey (NHANES). Participants included individuals over 18 years old with complete data on serum albumin concentration, red cell distribution, and MetS and its components. MetS was defined using the criteria established by the National Cholesterol Education Program Adult Treatment Panel III. The calculation formula for RAR is: RAR = Red cell distribution width (%)/serum albumin (g/dL). Study participants were stratified into four quartiles based on RAR levels. Logistic regression analysis and subgroup analysis were employed to explore the independent interaction between RAR and MetS, as well as investigate the relationship between RAR levels and the specific components of MetS. Finally, the receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of RAR for MetS. Results A total of 4899 participants were included in this study, comprising 2450 males and 2449 females; 1715 individuals (35.01%) were diagnosed with MetS. As the quartile of RAR increased, the proportion of individuals with MetS also increased. Spearman correlation analysis indicated a positive correlation between RAR and the insulin resistance index HOMA-IR. Logistic regression analysis, adjusting for multiple confounding factors, showed that each standard deviation increase in RAR was associated with a significant 1.665-fold increase (95% CI, 1.404–1.975; P

Abstract Background This study aimed to assess the relationship between multiple indicators of inflammation and erectile dysfunction through an analysis of data from the National Health and Nutrition Examination Survey (NHANES). This represents the first large-scale, cross-sectional investigation that explores this association by jointly analyzing various inflammatory markers. Methods We performed a cross-sectional analysis with NHANES data from 2001 to 2004. Erectile dysfunction (ED) was evaluated through a self-reported questionnaire and testosterone levels, while inflammatory markers were derived from standard blood test parameters. Our approach included multivariate logistic regression, subgroup analyses, generalized additive modeling (GAM), and smoothed curve fitting to evaluate the link between inflammatory markers (NLR, MLR, SII, SIRI, AISI) and ED. Additionally, we utilized receiver operating characteristic (ROC) curves to determine the diagnostic utility of these markers, comparing their area under the curve (AUC) values. Results A total of 3610 participants were included in this study, and the population-weighted ED patients were 18.91%. In the adjusted model, multiple logistic regression analysis showed a positive association between five inflammatory indicators (Ln-NLR, Ln-MLR, Ln-SII, Ln-SIRI, and Ln-AISI) and ED. Smoothed curve fitting showed a nonlinear positive correlation between the five inflammatory indicators and ED. Furthermore, subgroup analyses showed that this correlation was stronger in people older than 50 year. ROC curve analysis showed the highest diagnostic performance for the study outcome with MLR (AUC = 0.616, 95% CI: 0.5952–0.637), which was significantly better than SIRI, NLR, AISI, and SII. Conclusion MLR is potentially more effective than other biomarkers (NLR, SIRI, AISI, SII) in predicting ED. Men with elevated MLR levels should be particularly aware of their increased risk of developing ED.

Abstract Background The exact mechanisms underlying depression are not well understood. Chronic, low-grade inflammation is believed to play an important role in its development. The present study investigates the potential association between depressive symptoms and the neutrophil-to-lymphocyte ratio (NLR). Methods Seven data cycles of the National Health and Nutrition Examination Survey were extracted. Multivariable logistic regression and a generalized additive model were employed to determine the association. Results Thirty thousand eight hundred ninety-six subjects were analyzed. The results indicated that anhedonia and fatigue were significantly associated with NLR. Additionally, the generalized additive model results indicated a non-linear relationship between anhedonia, sleep disturbance and NLR. Subgroup analyses demonstrated that the correlation between anhedonia and NLR was significant in the above-60-year-old group (OR: 1.63, 95% CI: 1.14–2.33) and the male group (OR: 1.50, 95% CI: 1.07–2.10). Sleep disturbance was associated with NLR in the female group (OR: 1.36, 95% CI: 1.04–1.77). Fatigue was associated with NLR (OR: 1.30, 95% CI: 1.02–1.67) in the female group, as was the case in the non-Hispanic White group (OR: 1.32, 95% CI: 1.02–1.70). Conclusions There were associations between NLR and specific symptoms, and these associations varied across demographic subgroups. There was a non-linear association between anhedonia, sleep disturbance and NLR. These findings could potentially contribute to the advancement of precision medicine within the field of mental health.

Abstract Background Using neuroimaging techniques, growing evidence has suggested that the choroid plexus (CP) volume is enlarged in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Notably, the CP has been suggested to play an important role in inflammation-induced CNS damage under disease conditions. However, to our knowledge, no study has investigated the relationships between peripheral inflammation and CP volume in sporadic ALS patients. Thus, in this study, we aimed to verify CP enlargement and explore its association with peripheral inflammation in vivo in independent ALS cohorts. Methods Based on structural MRI data, CP volume was measured using Gaussian mixture models and further manually corrected in two independent cohorts of sporadic ALS patients and healthy controls (HCs). Serum inflammatory protein levels were measured using a novel high-sensitivity Olink proximity extension assay (PEA) technique. Xtreme gradient boosting (XGBoost) was used to explore the contribution of peripheral inflammatory factors to CP enlargement. Then, partial correlation analyses were performed. Results CP volumes were significantly higher in ALS patients than in HCs in the independent cohorts. Compared with HCs, serum levels of CRP, IL-6, CXCL10, and 35 other inflammatory factors were significantly increased in ALS patients. Using the XGBoost approach, we established a model-based importance of features, and the top three predictors of CP volume in ALS patients were CRP, IL-6, and CXCL10 (with gains of 0.24, 0.18, and 0.15, respectively). Correlation analyses revealed that CRP, IL-6, and CXCL10 were significantly associated with CP volume in ALS patients (r = 0.462 ∼ 0.636, p

Abstract Background Sepsis, a severe inflammatory response to infection, is a global health priority due to its high mortality and long-term disability rates. Its pathophysiology involves both inflammation and immune suppression. Managing sepsis requires significant healthcare resources and expenditure, with sepsis being a leading cause of hospital costs. Gut microbiotas play a crucial role in sepsis, and probiotics show promise in managing it by restoring microbial balance. Despite advances, targeted therapies for sepsis remain elusive, necessitating innovative approaches such as probiotic therapy. Method Fifty-four eligible patients with sepsis will be randomly assigned to either the synbiotic or placebo group. The synbiotic supplement, KidiLact, comprises ten probiotic strains and prebiotic fructooligosaccharides. Participants will receive two sachets daily for 7 days, mixed with sterile water and administered orally or via gavage. Inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) will be evaluated. Anthropometric measurements, nutritional assessment, biochemical analysis, and clinical evaluation will be conducted to assess treatment outcomes. Statistical analysis will be performed to compare results between the two groups, employing SPSS version 19 with a significance level of P

Abstract Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. The Toll-like receptor 4 (TLR4) signaling pathway is one of the most common inflammation-related pathways, and it has been demonstrated that TLR4 is highly expressed in adhesive tissues; however, the function of TLR4 in adhesion formation has not yet been studied. In the present study, the expression of TLR4 was first detected by immunohistochemical (IHC) and double-immunofluorescence staining in 40 mice, which were randomly divided into four groups, and sacrificed at 1, 3, 5 and 7 days after surgery. Subsequently, another 40 mice were randomly divided into five groups; with the exception of the sham group, the other groups were modeled and treated with saline that contained DMSO, sodium hyaluronate (HA), TAK-242 or TAK-242 + HA (applied to damaged peritoneal wounds). A total of 7 days after surgery, the mice were sacrificed and specimens were collected. Inflammation was detected by hematoxylin and eosin staining, and ELISA of transforming growth factor- β1 (TGF-β1) and interleukin-6 (IL-6); collagen deposition was examined by Masson staining and IHC staining of α-SMA; and reactive oxygen species (ROS) were detected by ROS staining and malondialdehyde (MDA) assay. The results revealed that TLR4 was highly expressed in the adhesive tissues at 3, 5 and 7 days after surgery. In addition, TAK-242 + HA treatment could reduce abdominal adhesion formation, exhibiting lower Nair’s score and inflammation scores, lower TGF-β1 and IL-6 levels, and lower collagen thickness and α-SMA levels compared with those in the control group. In addition, the TAK-242 + HA group had lower levels of ROS and MDA compared with those in the control group. The present study revealed that TLR4 was highly expressed in the process of adhesion formation and its inhibitor, TAK-242, combined with HA, could reduce adhesion formation by reducing inflammation and ROS, and alleviating collagen deposition.

This study explores the role of the von Hippel–Lindau (VHL) tumor suppressor gene and Lon protease in the development of clear cell renal carcinoma (ccRCC) through mechanisms involving inflammation and reactive oxygen species (ROS) accumulation in kidney cells. By examining the impact of VHL on the early stages of kidney cancer development, this research highlights the contributions of inflammation and ROS, as well as the involvement of Lon protease. The findings reveal increased Lon expression and ROS levels in VHL-knockdown HK-2 cells, along with elevated phospho-c-Jun N-terminal kinase (JNK) levels, emphasizing the complex interplay between VHL, Lon protease, inflammation, and ROS in kidney cell models. These insights point to potential therapeutic pathways for ccRCC.

Background: Esophageal cancer (EC) remains a significant health challenge in South Asia, with poor prognosis despite advancements in diagnostics and treatment. Identifying and validating prognostic factors is essential for improving patient outcomes. Methods: A prospective study was conducted with 146 biopsy-confirmed EC patients at the Dr. Ruth K.M. Pfau Civil Hospital, Karachi, Pakistan. Clinical and laboratory data were collected and analyzed using descriptive statistics, receiver operating characteristic (ROC) analysis, and the Chi-square test. Survival outcomes were assessed using Kaplan–Meier curves, log-rank tests, and Cox proportional hazard models for univariate and multivariate regression analyses, with statistical significance set at p ≤ 0.05. Results: Bivariate analysis showed significant associations of the neutrophil lymphocyte ratio (NLR) (p = 0.017), C-reactive protein to albumin ratio (CAR) (p = 0.033), red cell distribution width to platelet ratio (RPR) (p = 0.020), and systemic immune-Inflammation index (SII) (p = 0.009) with patient survival. Univariate analysis identified tumor length >10 cm (p = 0.016), T4 stage (p = 0.015), metastasis (p < 0.001), surgery not performed (p < 0.001), and SII (p = 0.022) as significant factors for survival, with higher SII linked to poorer overall survival (p = 0.020). Interestingly, in the multivariate model, only metastasis (p < 0.001) and surgery not performed (p = 0.011) remained significant. Conclusions: Immuno-inflammatory markers may be less pertinent prognostic factors for EC in the South Asian population.

Wenyi Li,1,2 Zhenguo Liu,1 Min Song,1 Zhenpeng Shi,1 Jihang Zhang,3 Junyu Zhou,1 Yidan Liu,1 Yun Qiao,4 Deshan Liu4 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Research Center for Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3Traditional Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Deshan Liu, Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 18560087381, Email liudeshan@sdu.edu.cnContext: Diabetic nephropathy (DN) and cognitive dysfunction (CD) are common complications of diabetes. Yi-Qi-Bu-Shen Recipe (YQBS) can effectively reduce blood glucose, improve insulin resistance, and delay the progression of diabetic complications. The underlying mechanisms of its effects need to be further studied.Objective: This study elucidates the mechanism of YQBS in DN with CD through network pharmacology and experimental validation.Materials and Methods: Protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Male Sprague-Dawley (SD) rats were divided into 6 groups: model, YQBS (2, 4, 8 g/kg), positive control (metformin, 200 mg/kg), and control; the DN model was established by high sugar and high fat diet combined with intraperitoneal streptozotocin injection. After the DN model was established, the rats were gavaged for 10 weeks. Serum, kidneys, and hippocampus tissues were collected to measure the expression levels of TLR4, NF-κB, TNF-α, and IL-6.Results: The network pharmacology analysis showed that quercetin and kaempferol were the main active components of YQBS. TNF and IL-6 were the key targets, and TLR4/NF-κB pathway was crucial to YQBS in treating DN complicated with CD. Experimental validation showed that the intervention of YQBS can reduce TNF-α and IL-6 in serum, and also significantly decreases the protein expression of TLR4 and NF-κB.Conclusion: YQBS exerts anti-inflammatory effects on DN with CD through TLR4/NF-κB pathway. This study provides a biological basis for the scientific usage of YQBS in inflammation diseases and supplies experimental evidence for future traditional Chinese medicine development.Keywords: Yiqi Bushen Recipe, diabetes nephropathy, cognitive dysfunction, network pharmacology, inflammation

Uriel Heresco-Levy,1,2 Jacob Haviv,1 Yehezkel G Caine1 1Herzog Medical Center, Jerusalem, Israel; 2Psychiatry Department, Hadassah Medical School, Hebrew University, Jerusalem, IsraelCorrespondence: Uriel Heresco-Levy, Herzog Medical Center, POBox 3900, Jerusalem, 91305, Israel, Tel +972-2-5316906, Fax +972-26075653, Email urielh@ekmd.huji.ac.ilAbstract: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by sustained airflow limitation that represents one of the main causes of disability in modern society. Depression affects approximately 40% of COPD patients. Both COPD and depression are associated with chronic systemic inflammation and their comorbidity represents a critical unmet treatment need. N-methyl-D-aspartate glutamatergic receptors (NMDAR) are well characterized in the central nervous system (CNS) and widely expressed in lung tissue and inflammation-related cells. Accumulating evidence indicates that pathologic NMDAR up-regulation, leading to pro-inflammatory pathways activation and tissue damage, may play a crucial role in chronic lung injury as well as in depression. D-cycloserine, a bacteriostatic antibiotic used since the 1950’s in tuberculosis, acts at therapeutic dosages also as a NMDAR functional antagonist and has antidepressant and anti-inflammatory effects. We hypothesize that NMDAR down-regulation may represent a unified molecular target for the treatment of COPD – depression comorbidity and may simultaneously alleviate both respiratory and depression symptomatology. We postulate that D-cycloserine treatment may achieve these dual – hit objectives and envisage that our hypotheses may apply to additional inflammation disorders that are frequently accompanied by depression.Keywords: inflammation, depression, chronic obstructive pulmonary disease, N-methyl-D-aspartate receptor, D-cycloserine

Mesenchymal stem cell (MSC)-based therapies have emerged as promising methods for regenerative medicine; however, how to precisely enhance their tissue repair effects is still a major question in the field. Circulating extracellular vesicles (EVs) from diseased states carry diverse pathological information and affect the functions of recipient cells. Based on this unique property, we report that disease-derived circulating EV (disease-EV) preconditioning is a potent strategy for precisely enhancing the tissue repair potency of MSCs in diverse disease models. Briefly, plasma EVs from lung or kidney tissue injuries were shown to contain distinctly enriched molecules and were shown to induce tissue injury-specific gene expression responses in cultured MSCs. Disease-EV preconditioning improved the performance (including proliferation, migration, and growth factor production) of MSCs through metabolic reprogramming (such as via enhanced oxidative phosphorylation and lipid metabolism) without inducing an adverse immune response. Consequently, compared with normal MSCs, disease-EV-preconditioned MSCs exhibited superior tissue repair effects (including anti-inflammatory and antiapoptotic effects) in diverse types of tissue injury (such as acute lung or kidney injury). Disease-derived EVs may serve as a type of “off-the-shelf” product due to multiple advantages, such as flexibility, stability, long-term storage, and ease of shipment and use. This study highlights the idea that disease-EV preconditioning is a robust strategy for precisely enhancing the regenerative capacity of MSC-based therapies.

Zhuhong Lai, Tingqiao Ye, Mingjun Zhang, Ying Mu Department of Cardiology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of ChinaCorrespondence: Ying Mu, Department of Cardiology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China, Email muyingdr123@yeah.netAbstract: Exosomes have grown as promising carriers for noncoding RNAs (ncRNAs) in the treatment of inflammation, particularly in conditions like ischemic stroke and myocardial infarction. These ncRNAs, which include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play a crucial role in regulating inflammatory pathways, presenting new therapeutic opportunities. In both ischemic stroke and myocardial infarction, inflammation significantly influences disease progression and severity. Exosomes can deliver ncRNAs directly to specific cells and tissues, providing a targeted approach to modulate gene expression and reduce inflammation. Their biocompatibility and low risk of inducing immune responses make exosomes ideal therapeutic vehicles. Ongoing research is focused on optimizing the loading of ncRNAs into exosomes, ensuring efficient delivery, and understanding the mechanisms by which these ncRNAs mitigate inflammation. In ischemic stroke, exosome-derived ncRNAs originate from various cell types, including neurons, M2 microglia, patient serum, genetically engineered HEK293T cells, and mesenchymal stromal cells. In the case of myocardial infarction, these ncRNAs are sourced from mesenchymal stem cells, endothelial cells, and patient plasma. These exosome-loaded ncRNAs play a significant role in modulating inflammation in both ischemic stroke and myocardial infarction. As this research advances, therapies based on exosomes may completely change how diseases linked to inflammation are treated, offering new avenues for patient care and recovery. This review explores the latest advancements in understanding how exosomes impact specific inflammatory components, with a particular emphasis on the role of ncRNAs contained in exosomes. The review concludes by highlighting the clinical potential of exosome-derived ncRNAs as innovative therapeutic and diagnostic tools.Keywords: exosomes, noncoding RNA, inflammation, ischemic stroke, myocardial infarction

旨在为油茶籽油与高油酸葵花籽油在化妆品中的应用提供数据支撑，通过体外3D表皮模型EpiKutis构建体外急性损伤及类湿疹表皮模型，以低温压榨高油酸葵花籽油和油茶籽油处理模型，检测其组织活力、炎症因子释放量、组织形态结构和胸腺基质淋巴细胞生成素（TSLP）含量，评价高油酸葵花籽油和油茶籽油的抗炎、抗刺激、抗湿疹功效。结果表明：高油酸葵花籽油与油茶籽油对模型组织活力均无显著影响；油茶籽油能显著降低模型炎症因子释放量，而高油酸葵花籽油不能显著降低模型炎症因子释放量；高油酸葵花籽油与油茶籽油对模型组织形态结构均有一定改善；高油酸葵花籽油与油茶籽油均能极显著降低模型TSLP含量。综上，油茶籽油与高油酸葵花籽油对皮肤刺激性炎症均具有一定的抑制和缓解作用，具有显著的抗湿疹功效；同时，油茶籽油对皮肤刺激性损伤具有一定的抑制和缓解作用。Aiming to provide data support for the application of oil-tea camellia seed oil and high oleic acid sunflower seed oil in cosmetics,3D epidermal model EpiKutis was used to construct acute injury and eczema-like epidermal models in vitro, the models were treated by cold-pressed high oleic acid sunflower seed oil and oil-tea camellia seed oil, and the anti-inflammatory, anti-irritation and anti-eczema effects of high oleic acid sunflower seed oil and oil-tea camellia seed oil were evaluated by examining the tissue vitality, the release of inflammatory factors, the changes of tissue morphology and structure, and the content of thymus stromal lymphogenesis hormone (TSLP) of the models.The results showed that high oleic acid sunflower seed oil and oil-tea camellia seed oil had no significant effect on tissue vitality, oil-tea camellia seed oil could significantly reduce the release of inflammatory factors, but high oleic acid sunflower seed oil could not. High oleic acid sunflower seed oil and oil-tea camellia seed oil could improve tissue morphology and structure to some extent, and significantly reduce the content of TSLP. To sum up, both oil-tea camellia seed oil and high oleic acid sunflower seed oil have certain inhibition and relief effects on skin irritant inflammation, and have significant anti-eczema effects. At the same time,oil-tea camellia seed oil also has a certain inhibition and relief effect on skin irritant damage.

The gut microbiota harbors a complex ecosystem of bacteria that govern host health homeostasis. Alterations to the intestinal environment, known as gut dysbiosis, is associated with several diseases. Targeting the gut with microbiome-engineered therapeutics, such as probiotics, is a promising approach to restore microbial homeostasis and host health. Probiotics can effectively improve the gut environment, although strain-specific mechanisms remain largely unknown. Thus, this study aims to identify beneficial action of select probiotics to modulate the gut environment through antioxidative and anti-inflammatory properties. To this end, we tested the interaction among three probiotic strains – Lactobacillus gasseri A237 (LgA237), Lactobacillus plan-tarum WCFS1 (LpWCFS1) and Lactobacillus fermentum NCIMB 5221 (Lf5221) – and a human intestinal epithelial cell line, HT-29, for adhesion properties, radical scavenging abilities and anti-inflammatory activities. All three probiotics adhere well to HT-29 cells, indicating proper gut colonization. LpWCFS1 demonstrated the greatest adhesion capacity (68.3%), followed by LgA237 (35.5%) and Lf5221 (25.9%). The probiotics also exhibit excellent antioxidant properties via DPPH radical scavenging activity, comparable to quercetin, a known and potent antioxidant. Moreover, LgA237, LpWCFS1 and Lf5221 decrease interleukin-8 expression in lipopolysaccharide (LPS)-damaged HT-29 cells (41.19, 34.53 and 14.80% reduction, respectively), compared to non-treated cells. Further investigation of LpWCFS1 and LgA237 revealed a significant (p

Abstract Introduction Mesenchymal stromal cell (MSC)-based cell therapy is a promising approach for various inflammatory disorders based on their immunosuppressive capacity. Osteopontin (OPN) regulates several cellular functions including tissue repair, bone metabolism and immune reaction. However, the biological function of OPN in regulating the immunosuppressive capacity of MSCs remains elusive. Objectives This study aims to highlight the underlying mechanism of the proinflammatory cytokines affect the therapeutic ability of MSCs through OPN. Methods MSCs in response to the proinflammatory cytokines were collected to determine the expression profile of OPN. In vitro T-cell proliferation assays and gene editing were performed to check the role and mechanisms of OPN in regulating the immunosuppressive capacity of MSCs. Inflammatory disease mouse models were established to evaluate the effect of OPN on improving MSC-based immunotherapy. Results We observed that OPN, including its two isoforms iOPN and sOPN, was downregulated in MSCs upon proinflammatory cytokine stimulation. Interestingly, iOPN, but not sOPN, greatly enhanced the immunosuppressive activity of MSCs on T-cell proliferation and thus alleviated the inflammatory pathologies of hepatitis and colitis. Mechanistically, iOPN interacted with STAT1 and mediated its deubiquitination, thereby inducing the master immunosuppressive mediator inducible nitric oxide synthase (iNOS) in MSCs. In addition, iOPN expression was directly downregulated by activated STAT1, which formed a negative feedback loop to restrain MSC immunosuppressive capacity. Conclusion Our findings demonstrated that iOPN expression modulation in MSCs is a novel strategy to improve MSC-based immunotherapy.

Abstract Introduction Non-alcoholic fatty liver disease (NAFLD) and obesity have become one of the most common chronic diseases, and the global prevalence is increasing year by year. Both are accompanied by hypersensitive C-reactive protein (hs-CRP). At present, there are many predictors of NAFLD. Exploring the relationship between hs-CRP and nonalcoholic fatty liver disease in non-obese people will be helpful for risk prediction and clinical screening in high-risk populations. Objective To explore the relationship between levels of serum hs-CRP and the presence of NAFLD in non-obese people. Methods A total of 6558 participants who underwent physical examination from March 2017 to November 2017. Multivariate logistic regression was utilized to analyze the risk factors associated with NAFLD. Results This study including 4240 males and 2318 females ranging from 20 to 94 years. In 1396 patients with NAFLD, the prevalence rate was 21.3%, among which 1056 (24.9%) males and 340 (14.7%) females had NAFLD. The prevalence of NAFLD was much higher in males compared to females (χ 2 = 93.748, P

Abstract Background Porphyromonase gingivalis (P. gingivalis) is a type of bacteria that causes periodontitis, which is strongly correlated with systemic diseases such as diabetes. However, the effect of hyperglycemia on periodontitis are unclear. The present study examined the effects of high glucose levels on the response to P. gingivalis infection. Results The expression of P. gingivalis-induced interleukin-1β (IL-1β) and inflammasomes increased as the glucose concentration increased. High glucose conditions suppressed P. gingivalis–induced autophagy in human acute monocytic leukemia cell line (THP-1) macrophages. Zingerone increased autophagy and alleviated P. gingivalis-induced inflammatory response in THP-1 macrophages under high glucose conditions. In addition, P. gingivalis- induced inflammation in bone marrow-derived macrophages of diabetic mice was higher than in wild-type mice, but a zingerone treatment decreased the levels. Alveolar bone loss due to a P. gingivalis infection was significantly higher in diabetic mice than in wild-type mice. Conclusions High-glucose conditions aggravated the inflammatory response to P. gingivalis infection by suppressing of autophagy, suggesting that autophagy induction could potentially to treat periodontitis in diabetes. Zingerone has potential use as a treatment for periodontal inflammation induced by P. gingivalis in diabetes patients.

Abstract Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p

Abstract Background Cerebrovascular accidents (CVAs), or strokes, are major global health concerns associated with oxidative stress, inflammation, and gastrointestinal complications. This study aimed to explore the impact of postbiotic supplementation in CVA patients, specifically in terms of oxidative stress, inflammation, and clinical outcomes, as an alternative to probiotics with potential advantages. Method A prospective, single-center, randomized, controlled trial was conducted with 120 CVA patients in Iran. These patients were admitted to the ICU to assess the severity of their strokes. Patients were randomly assigned to receive either postbiotic supplementation (n = 60) or a placebo (n = 60). Various biomarkers related to oxidative stress, inflammation, and clinical outcomes were assessed. Data on demographic characteristics, nosocomial infections, and laboratory measurements were collected. Gut microbiota analysis was also performed on fecal samples. Results After the 7-day intervention, postbiotic supplementation resulted in significant improvements in inflammatory markers, oxidative stress, and a reduced incidence of pneumonia compared with those in the control group, with the postbiotic group demonstrating notable decreases in the serum IL-1β levels (-1.79; 95% CI: = -2.9 to -0.64, p = 0.002 ), MDA levels (-30.5; 95% CI: -54.8 to -6.1, p = 0.015), Hs-CRP levels (-0.67; 95% CI:-1.1 to -0.26 mg/dl, p = 0.001) and TAC levels (62.5; 95%CI: 34.1 to 90.9, p

Abstract The C-reactive protein-albumin-lymphocyte (CALLY) index, which integrates albumin, lymphocytes, and C-reactive protein levels, has emerged as a novel method to assess nutritional and inflammatory statuses in patients. This study examined the correlation between the CALLY index and sarcopenia risk using two cohorts: 1804 community dwellers from the NHANES database in the United States and 139 patients from the Department of Gerontology at Kunshan Hospital, China. In the US community cohort, RCS curve analysis was used to examine the non-linear relationship between inflammatory/nutritional markers and sarcopenia, subgroup analysis was also conducted. Logistic regression was employed to evaluate the association between the CALLY index and the risk of sarcopenia in both cohorts. Results demonstrated a significant non-linear relationship between the CALLY index and the risk of sarcopenia (P

Abstract Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639–1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633–1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5–15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis.

Abstract Our research explores the detrimental effects of microplastic (MP) exposure on adipose tissue aging and function, emphasizing the potential health risks associated with environmental pollutants. Utilizing both in vivo and in vitro models, we discovered that MPs accumulate in adipose tissues, leading to cellular senescence, inflammation, and hindered adipogenic differentiation. Notably, our findings demonstrate that MPs prompt an aging response in both epididymal and inguinal white adipose tissue, increase senescence-associated β-galactosidase activity, and upregulate key senescence and inflammatory markers. Furthermore, we show that MPs disrupt normal adipogenic differentiation by reducing lipid droplet formation and downregulating critical adipogenic markers. These insights highlight the urgent need for further investigation into the long-term consequences of MP pollution on biological aging and underscore the importance of developing public health strategies to mitigate these effects.

Abstract In patients with major depressive disorder, various functional areas are impaired, negatively impacting the quality of life. Remission can restore pre-depression functions; however, some patients may still have residual impairments. Distinguishing between near-normal recovery and residual impairment helps identify those at a high risk of relapse risk and helps tailor treatment. Accordingly, we aimed to discover and validate biomarkers that distinguish between near-normal recovery and residual impairment in remission states through serum proteome analysis. Pooled serum and individual serum samples from three groups (depression status, remission status with residual impairment, and remission status with normal recovery) were analyzed using liquid chromatography-tandem mass spectrometry. The combination of four proteins—antithrombin-III, serum amyloid A4 protein, C1q subcomponent subunit B, and serum amyloid P-component—was selected as a candidate biomarker. The trend of protein changes suggests complement C1q subcomponent subunit B and serum amyloid P-component as potential biomarkers for distinguishing remission from residual impairment. Changes in complement C1q subcomponent subunit B and serum amyloid P-component suggest that the complement system and inflammation-related immune mechanisms are associated with residual impairment in remittent major depressive disorder.

Abstract Although Alzheimer’s disease (AD) and intracranial aneurysm (IA) were two different types of diseases that occurred in the brain, ruptured IA (RIA) survivors may experience varying degrees of cognitive dysfunction. Neither AD nor IA is easily recognizable by an early onset so that the incidence of adverse clinical outcomes would be on the rise. Therefore, we focused on the exploration of the shared genes and molecular mechanisms between AD and IA, which would be significant for the efficiency of co-screening and co-diagnosis. Two GEO datasets were selected for the weighted gene co-expression network analysis (WGCNA) and differentially expressed gene screening, obtaining 78 overlapped genes. Next, 9 hub genes were identified by the protein-protein interaction network, including PIK3CA, GAB1, IGF1R, PLCB1, PGR, PDGFRB, PLCE1, FGFR3, and SYNJ1. The interactions among the hub genes, miRNA, and TFs were also explored. Meanwhile, we performed GO and KEGG pathway enrichment analyses for the results of WGCNA and hub genes, which showed that the Ras signaling and Rap1 signaling were the main shared pathogenesis. In conclusion, the present bioinformatics analysis revealed that AD and IA had the shared genes and molecular mechanisms, and these outcomes were associated with inflammation and calcium homeostasis, which could provide research clues for further studies.

Abstract Periodontitis exacerbates Alzheimer’s disease (AD) through multiple pathways. Both periodontitis and AD are intricately correlated to intestinal homeostasis, yet there is still a lack of direct evidence regarding whether periodontitis can regulate the progression of AD by modulating intestinal homeostasis. The current study induced experimental periodontitis in AD mice by bilaterally ligating the maxillary second molars with silk and administering Pg-LPS injections in APPswe/PS1ΔE9 (APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. Gut microbiota was analyzed and colon tissue were also evaluated. Then, fecal microbiota from mice with periodontitis was transplanted into antibiotic-treated mice to confirm the effects of periodontitis on AD and the potential mechanism was explored. The results indicated periodontitis exacerbated cognitive impairment and anxious behaviour in APP/PS1 mice, with increased Aβ deposition, microglial overactivation and neuroinflammation in brain. Moreover, the intestinal homeostasis of AD mice was altered by periodontitis, including affecting gut microbiota composition, causing colon inflammation and destroyed intestinal epithelial barrier. Furthermore, AD mice that underwent fecal transplantation from mice with periodontitis exhibited worsened AD progression and disrupted intestinal homeostasis. It also impaired intestinal barrier function, elevated peripheral inflammation, damaged blood-brain barrier (BBB) and caused neuroinflammation and synapses impairment. Taken together, the current study demonstrated that periodontitis could disrupt intestinal homeostasis to exacerbate AD progression potential via causing gut microbial dysbiosis, intestinal inflammation and intestinal barrier impairment to induce peripheral inflammation and damage BBB, ultimately leading to neuroinflammation and synapse impairment. It underscores the importance of maintaining both periodontal health and intestinal homeostasis to reduce the risk of AD.

Abstract Background The purpose of this research was to evaluate the efficacy of Narcotrend (NT) monitoring on cognitive dysfunction in patients undergoing anesthesia blockade for gastrointestinal tumors and its effect on cerebral oxygen metabolism and inflammatory response. Methods Patients preparing to undergo resection of gastrointestinal tumor resection were included and randomly divided into a control group (depth of anesthesia assessed by physician experience) and a research group (depth of anesthesia monitored by NT). HR and MAP were monitored at the preoperatively (T0), 12 h postoperative (T1), 24 h postoperative (T2), and 48 h postoperative (T3) stages. MMSE score was recorded to assess changes in cognitive function. Intracerebral oxygenation indicators (CjvO2, CERO2, and rSO2) were assessed by a blood gas analyzer. ELISA assay was conducted to explore the serum inflammatory indexes (CRP, IL-1β, and TNF-α) and neurological function indicators (NSE and MBP). Results MAP was higher in the research group than in the control group at T1 and T2 (P

Abstract Background Congenital diaphragmatic hernia (CDH) is a rare disease that affects the development of the diaphragm, leading to abnormal lung development. Unfortunately, there is no established therapy for CDH. Retinoic acid pathways are implicated in the ethology of CDH and macrophages are known to play a role in repairing organ damage. Methods We have analyzed the effect of several Toll like receptor (TLR) ligands in the nitrofen-induced CDH model in pregnant rats widely used to study this disease and in the G2-GATA4Cre;Wt1fl/fl CDH genetic mice model. Morphometric and histological studies were carried out. Immune cell infiltration was assayed by immunochemistry and immunofluorescence and retinoic pathway gene expression analyzed in vivo and in vitro in macrophages. Results We found that administering a single dose of atypical TLR2/4 ligands (CS1 or CS2), 3 days after nitrofen, cured diaphragmatic hernia in 73% of the fetuses and repaired the lesion with complete diaphragm closure being on the other hand nontoxic for the mothers or pups. Moreover, these immunomodulators also improved pulmonary hypoplasia and alveolar maturation and vessel hypertrophy, enhancing pulmonary maturity of fetuses. We also found that CS1 treatment rescued the CDH phenotype in the G2-GATA4Cre;Wt1fl/fl CDH genetic mice model. Only 1 out of 11 mutant embryos showed CDH after CS1 administration, whereas CDH prevalence was 70% in untreated mutant embryos. Mechanistically, CS1 stimulated the infiltration of repairing M2 macrophages (CD206+ and Arg1+) into the damaged diaphragm and reduced T cell infiltration. Additionally, those TLR ligands induced retinol pathway genes, including RBP1, RALDH2, RARα, and RARβ, in the affected lungs and the diaphragm and in macrophages in vitro. Conclusions Our research has shown that TLR ligand immunomodulators that influence anti-inflammatory macrophage activation can be effective in treating CDH, being nontoxic for the mothers or pups suggesting that those TLR ligands are a promising solution for CDH leading to orphan drug designation for CS1. The immune system of the fetus would be responsible for repairing the damage and closure of the hernia in the diaphragm and enhanced proper lung development after CS1 treatment.

Abstract Introduction Several blood markers of inflammation are elevated in prostate cancer (PCa) and have prognostic value. Little is known about the relationship between these markers, PCa, and other factors associated with chronic inflammation, such as smoking and obesity. We analyzed the interaction between neutrophil and platelet counts indexed to lymphocyte count (NLR and PLR, resp.) and clinically significant PCa (csPCa), accounting for the potential confounding factors of systemic inflammation. Methods NLR and PLR were evaluated in a multicenter prospective study in 443 patients. CsPCa was defined as a Gleason ≥ 4 + 3. Differences between patients with csPCa and non-csPCA were evaluated using the chi-square test, analysis of variance or the Kruskal-Wallis test. Multivariable logistic regression analysis adjusted for smoking, hypertension, diabetes, and cardiovascular disease, and in separate models, either body mass index or waist-to-hip ratio was used to characterize the relationship between inflammation and csPCa. Results None of the factors such as plateletcrit, NLR, and PLR were significantly different between patients with csPCa or non-significant PCa. After adjustment, there was no association between PLR, NLR, plateletcrit or platelet count and csPCa. In an exploratory analysis, there was no association between markers of inflammation and PSA levels > 10 ng/mL. When testing different NLR cutoffs to predict csPCa in ROC analysis, none reached a clinically meaningful value. Conclusion In contrast to previous studies, we found no significant association between easily available blood markers of inflammation and indices of PCa aggressiveness. Further research is required to determine whether inflammation promotes PCa. (ClinicalTrials.gov: NCT03127631. Date of registration: April 25, 2017.

Abstract Background The main characteristic of asthma is chronic inflammation. We examined cellular senescence by histology and molecular assay in the lungs of a rat model of asthma. This model comprises sensitization by several intraperitoneal injections of ovalbumin with aluminium hydroxide, followed by aerosol challenges every other day. Results Data showed that asthma induction caused histological changes including, hyperemia, interstitial pneumonia, fibrinogen clots, and accumulation of inflammatory cells in the pleura. There is an elevation of IL-1β and NF-kB proteins in the asthmatic group (P

Abstract Background Breast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients. Methods Plasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements. Results Before initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ2 = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15–48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy. Conclusion Postmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy. Trial registration The clinical trial (registration number NCT03784651) was registered on www.clinicaltrials.gov on 24 December 2018.

Glaucoma is one of the main causes of irreversible vision loss worldwide, its prevalence is increasing with age, reaching 10 % in individuals over 90 years old. Combined surgical treatment of cataract and glaucoma has proven to be safe and effective, reducing overall treatment costs. Minimally invasive glaucoma surgery (MIGS) combined with cataract surgery has become a popular alternative to traditional methods. One such intervention is endoscopic laser cyclodestruction (ELCD), aimed at reducing the production of aqueous humor.Objective: To evaluate the conditions for achieving maximum efficacy and safety of endoscopic laser cyclodestruction (ELCD) in the combined surgical treatment of glaucoma and cataract.Methods. A clinical study was conducted involving 110 patients (56 males and 54 females) with a mean age of 73.7 years, who underwent combined surgery (phacoemulsification + ELCD). Inclusion criteria were stages I-IV glaucoma and initial complicated cataract, while exclusion criteria included lens subluxation and presence of uveal processes or their consequences. ELCD was performed using the Endo Optiks Inc (USA) video-endoscopic ophthalmic laser device. Patients were evaluated preoperatively and followed up at 1, 3, 6, 9, 12, 18, 24, 36, 48, and 60 months postoperatively. The primary safety outcomes included the frequency of intraand postoperative complications, and efficacy outcomes were based on intraocular pressure (IOP) reduction.Results. No hemorrhagic complications were noted. An inflammatory reaction was observed in 18.2% cases, which was managed with subconjunctival injections of prourokinase. The frequency of postoperative IOP elevation correlated negatively with preoperative IOP levels. ELCD demonstrated a statistically significant reduction in IOP and medication burden, with a complete success rate of 52.7 % and a partial success rate of 90.3 %. The extent of cyclodestruction (180–360°) did not significantly affect IOP reduction outcomes.Conclusion. ELCD, performed as part of combined surgery for glaucoma and cataract, proved to be effective and safe, achieving significant IOP reduction and decreasing the need for antiglaucoma medications. Recommendations include avoiding vaporization effects during surgery and preferring patients with preoperative IOP above 27 mm Hg for optimal outcomes.

Abstract Introduction VEXAS syndrome is a rare condition characterized by somatic mutations in the ubiquitin‐like modifier activating enzyme 1 (UBA1) gene and a constellation of clinical/morphologic findings, including the presence of cytoplasmic vacuoles within bone marrow hematopoietic cells. Methods and objectives In this report, we present a case of a male patient diagnosed with VEXAS‐associated myelodysplastic syndrome following the detection of a non‐canonical UBA1 p.Gly477Ala variant whose bone marrow biopsy revealed a conspicuous absence of cytoplasmic vacuolization in hematopoietic cells. This case prompts a comprehensive review of the existing literature on the significance and pathobiology of vacuolization in the context of VEXAS and UBA1 mutations.

Maodong Leng,1 Lu Xu,1 Zhen Dong,2 Junmei Yang1 1Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou, Henan, People’s Republic of China; 2Pediatric Internal Medicine Department, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Junmei Yang, Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, No. 33 of Longhu Outer Street, Zhengzhou East District, Zhengzhou, Henan Province, People’s Republic of China, Email yangjunmei7683@163.comObjective: Mycoplasma pneumoniae (M. pneumoniae) pneumonia presses a serious threat on children’s health. This study was aimed to investigate the clinical significance of pathogen loads and macrolide resistance levels for macrolide-resistant M. pneumoniae (MRMP)-induced pneumonia in children.Methods: Serum levels of inflammatory markers including lactic dehydrogenase (LDH), D-dimer, C-reactive protein (CRP) were tested. RT‒PCR was used for the detection of M. pneumoniae infection and the macrolide resistance levels. The patients were classified into high pathogen load and low pathogen load groups based on the Ct values of the p1 gene, and high macrolide resistance level and low macrolide resistance level groups based on the relative levels of macrolide resistance associated mutations to that of the p1 gene. The rates of alternative antibiotic use and hospitalization days were recorded, and the leukocyte counts were tested.Results: The rates of elevated inflammatory markers from high to low were LDH, CRP and D-dimer. The Ct values of the p1 gene ranged from 19 to 35, and patients with higher pathogen loads had greater rates of alternative antibiotic use; higher levels of LDH, D-dimer, CRP and neutrophil counts (NEUT); and longer hospitalization durations. The range of the macrolide resistance levels was 0.31– 2.11, and the rates of alternative antibiotic use, NEUT, CRP and D-dimer levels were higher in patients with higher macrolide resistance levels.Conclusion: LDH was a more frequently elevated serum inflammatory marker than D-dimer and CRP, and the pathogen load and macrolide resistance levels possessed important clinical significance for MRMP-induced pneumonia in children.Keywords: Mycoplasma pneumoniae pneumonia, children, inflammation, macrolide resistance levels, pathogen load

Objective To investigate the clinical value of peripheral eosinophil count (PEC) in predicting the outcome of diabetic nephropathy (DN). Methods A retrospective cohort trial was conducted on 220 DN patients identified by renal biopsy in Department of Nephrology of Second Affiliated Hospital from Army Medical University from March 2021 to March 2023. Clinical data, results of routine blood test and renal function were collected. X-tile bioinformatics software version 3.6.1 was used to determine the optimal cut-off value of PEC for predicting survival. Cox proportional hazards model and Kaplan-Meier survival analysis were applied to analyze the prognosis. Results The level of PEC in DN patients was positively correlated with the levels of serum creatinine (Scr) (r=0.245), blood urea nitrogen (BUN) (r=0.237) and blood uric acid (UA) (r=0.252), and negatively with estimated glomerular filtration rate (eGFR) (r=-0.236). According to the optimal PEC cut-off value, DN patients were divided into high-level group (>0.29×109/L, n=41) and low-level group (≤0.29×109/L, n=179). The levels of Scr (P < 0.001), BUN (P=0.001) and UA (P=0.005) were significantly higher, while the eGFR (P < 0.001) was obviously lower in the high-level group than the low-level group. Multivariate Cox regression analysis showed that the high level of PEC was associated with poor prognosis of DN (HR=2.20, 95%CI: 1.05~4.60, P=0.036). Kaplan-Meier survival analysis demonstrated that the incidence of end-stage renal disease (ESRD) was notably higher in the high-level group than the low-level group (P=0.024). Conclusion PEC level of DN patients is closely associated with the progression and prognosis of DN, and the count is a potential biomarker for predicting the prognosis of DN.

Sleep regulates inflammatory responses, and the innate immune system affects sleep. Interleukin-1 beta, tumor necrosis factor alpha, growth hormone-releasing hormone, prolactin, and nitric oxide are somnogenic substances. Sleep deprivation, such as chronic insomnia or obstructive sleep apnea, affects cytokine production, glial function, natural killer cell activity, and inflammasome function. This review will discuss the relationship between sleep and innate immunity.