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We have previously demonstrated a rapid secretion of matrix metalloproteinase-2 (MMP-2) in the ischemic brain. Since Scube2 can interact with Sonic hedgehog (Shh) to maintain blood-brain barrier (BBB) integrity via regulating the interaction between brain capillary endothelial cells (ECs) and perivascular astrocytes, and it is also a substrate of MMP-2, we hypothesized that the secreted MMP-2 could degrade Scube2 and contribute to ischemic BBB disruption. Using an in vitro ischemic model of 90-min oxygen-glucose deprivation/3-h reoxygenation (OGD/R) and an in vivo mouse stroke model of 90-min middle cerebral artery occlusion (MCAO) with 3-h reperfusion, we established an important role of MMP-2-mediated Scube2 degradation in early ischemic BBB disruption. Exposure of C8-D1A cells and bEnd.3 cells to OGD/R increased MMP secretion in both cells, and C8-D1A cells appeared to secrete more MMPs than bEnd.3 cells. Co-IP and double-immunostaining revealed that Scube2 co-localized well with MMP-2 in C8-D1A cells and could be pulled down by MMP-2 antibodies. In MCAO mice, Scube2 protein showed a drastic reduction in ischemic brain tissue, which was accompanied by suppressed expression of Shh and its downstream molecules. Of note, specific knockdown of astrocytic Scube2 with AAV-shScube2 augmented MCAO-induced Shh suppression and exacerbated BBB leakage and inflammatory reactions in the ischemic brain. Last, incubation of bEnd.3 cells with conditioned medium derived from OGD-treated C8-D1A cells led to a significant inhibition of the Shh pathway in bEnd.3 cells and degradation of VE-cadherin and ZO-1. Inhibition of MMP-2 with SB-3CT or over-expression of Scube2 with plasmids in C8-D1A cells alleviated the above effect of C8-D1A cells-derived conditioned medium. Taken together, our data indicate that ischemia-induced secretion of MMP-2 may contribute to early BBB disruption in ischemic stroke via interrupting the shared Scube2-Shh pathway between brain capillary ECs and perivascular astrocytes., (© 2023 International Society for Neurochemistry.)

Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: The value of the systemic immune‐inflammatory index (SII) in assessing adverse outcomes in various cardiovascular diseases has been extensively discussed. This study aims to evaluate the predictive value and risk stratification ability of SII for 30 day mortality in patients with acute decompensated heart failure (ADHF). Methods: This analysis included 1452 patients hospitalized for ADHF, all the participants being part of the China Jiangxi‐acute decompensated heart failure1 project. The risk stratification capability of the SII in patients with ADHF, as well as its correlation with the 30 day mortality risk among ADHF patients, was evaluated utilizing Kaplan–Meier survival analysis and multivariable Cox regression models. A restricted cubic spline was employed to model the dose–response relationship between the two, and the receiver operating characteristic curve was utilized to assess the predictive ability of SII for 30 day mortality. Results: The Kaplan–Meier analysis revealed that the risk of mortality in the high SII group (SII ≥ 980 × 109/L) was significantly greater than that in the low SII group (SII < 980 × 109/L, log‐rank P < 0.001). After adjusting for various confounding factors, a higher SII was associated with an increased risk of 30 day mortality in ADHF patients [hazard ratio (HR) = 2.03, 95% confidence interval (CI): 1.34–3.08]. Further restricted cubic spline analysis revealed a non‐linear dose–response relationship between the two (P for non‐linear = 0.006). Receiver operating characteristic analysis demonstrated that SII had a high accuracy in predicting 30 day mortality events in ADHF patients (AUC = 0.7479), and the optimal predictive threshold was calculated to be 980 × 109/L, a sensitivity of 0.7547 and a specificity of 0.7234. Conclusions: This study found a significant positive association between SII and 30 day all‐cause mortality in ADHF patients. We determined the SII cut‐off point for predicting 30 day all‐cause mortality in patients with ADHF to be 980 × 109/L. [ABSTRACT FROM AUTHOR]

Introduction: Monoiodoacetate (MIA)-induced osteoarthritis (OA) is the most commonly used rodent model for testing anti-OA drug candidates. Herein, we investigated the effects of our patented multitarget drug candidate SZV-1287 (3- (4,5-diphenyl-1,3-oxazol-2-yl) propanal oxime) that is currently under clinical development for neuropathic pain and characterized the mouse model through complex functional, in vivo imaging, and morphological techniques. Methods: Knee OA was induced by intraarticular MIA injection (0.5 and 0.8 mg). Spontaneous pain was assessed based on weight distribution, referred pain by paw mechanonociception (esthesiometry), edema by caliper, neutrophil myeloperoxidase activity by luminescence, matrix metalloproteinase activity, vascular leakage and bone remodeling by fluorescence imaging, bone morphology by micro-CT, histopathological alterations by semiquantitative scoring, and glia activation by immunohistochemistry. Then, SZV-1287 (20 mg/kg/day) or its vehicle was injected intraperitoneally over a 21-day period. Results: MIA induced remarkably decreased thresholds of weight bearing and paw withdrawal, alterations in the tibial and femoral structures (reactive sclerosis, increased trabeculation, and cortical erosions), histopathological damage (disorganized cartilage structure, hypocellularity, decreased matrix staining and tidemark integrity, and increased synovial hyperplasia and osteophyte formation), and changes in the astrocyte and microglia density in the lumbar spinal cord. There were no major differences between the two MIA doses in most outcome measures. SZV-1287 inhibited MIA-induced weight bearing reduction, hyperalgesia, edema, myeloperoxidase activity, histopathological damage, and astrocyte and microglia density. Conclusion: SZV-1287 may have disease-modifying potential through analgesic, anti-inflammatory, and chondroprotective effects. The MIA mouse model is valuable for investigating OA-related mechanisms and testing compounds in mice at an optimal dose of 0.5 mg. [ABSTRACT FROM AUTHOR]

Background: The uncertainty regarding the correlation between the weight-adjusted waist index (WWI) and diabetes within the National Health and Nutrition Examination Survey (NHANES) necessitates further exploration. As indicators of obesity, the differences in the intensity of association between WWI, body mass index (BMI), and waist circumference (WC) with diabetes are worth exploring. This investigation is undertaken to elucidate the association between WWI and diabetes in the NHANES dataset and to compare the extent to which BMI, WC, and WWI were closely associated with diabetes. Then, choose an obesity index that is more strongly associated with diabetes. Methods: A comprehensive cross-sectional stratified survey of 7,973 participants from the 2017–2020 NHANES was conducted. WWI is an anthropometric measure based on WC and weight. The formula is WWI (cm/√kg) = WC/√weight. The association between WWI and diabetes was investigated using weighted multiple logistic regression, smooth curve fitting, stratified analysis, and interaction testing. Results: The participants' average age was 50.84±17.34 years, and 50.68% of them were female. The detection rate of diabetes was 15.11%. This positive association was particularly notable among non-diabetic patients. For each unit increase in BMI and WC as continuous variables, the likelihood of developing diabetes in the fully adjusted model increased by 5% (OR = 1.05; 95%CI, 1.03–1.07) and 3% (OR = 1.03; 95%CI, 1.02–1.04), respectively, but for each one-unit increase in WWI, the likelihood of developing diabetes increased by 111% (OR = 2.11; 95% CI, 1.68–2.65). Tests of interactions revealed that in various subgroups, the association between diabetes and WWI remained steady. Conclusions: We analyzed 2017–2020 NHANES data to explore the link between WWI and diabetes, finding a consistent positive correlation. The correlation between WWI and diabetes was stronger than that between WC and BMI. WWI seems to offer better potential aid in disease prevention and diagnosis. [ABSTRACT FROM AUTHOR]

Although liver transplantation (LT) is an effective strategy for end-stage liver diseases, the shortage of donor organs and the immune rejection hinder its widespread implementation in clinical practice. Mesenchymal stem cells (MSCs) transplantation offers a promising approach for patients undergoing liver transplantation due to their immune regulatory capabilities, hepatic protection properties, and multidirectional differentiation potential. In this review, we summarize the potential applications of MSCs transplantation in various LT scenarios. MSCs transplantation has demonstrated effectiveness in alleviating hepatic ischemia-reperfusion injury, enhancing the viability of liver grafts, preventing acute graft-versus-host disease, and promoting liver regeneration in split LT therapy. We also discuss the clinical progress, and explore the immunomodulatory functions of MSCs in response to both adaptive and innate immune responses. Furthermore, we emphasize the interactions between MSCs and different immune cells, including T cells, B cells, plasma cells, natural killer cells, dendritic cells, Kupffer cells, and neutrophils, to provide new insights into the immunomodulatory properties of MSCs in adoptive cell therapy. [ABSTRACT FROM AUTHOR]

Aims: The aim of the research was to look into the connection between the occurrence of gallstones in adult US citizens and lipid accumulation products (LAP). Methods: We conducted a cross-sectional study of 3,582 U.S. adults with relevant indicators collected from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) database. Multifactorial logistic regression was used to investigate the linear relationship between LAP and gallstone incidence, while smoothed curve fitting was used to describe the nonlinear relationship, and subgroup and interaction analyses were used to evaluate the potential differences between groups. Results: Among the 3582 participants aged ≥ 20 years included, there was a positive association between LAP and gallstones. Following adjustments for all covariates, the likelihood of getting gallstones rose by 29% for each unit rise in log2-LAP (OR = 1.29, 95% CI: 1.13‒1.49). Compared to those in the lowest tertile, those in the highest LAP tertile had a significantly higher risk of developing gallstones (OR = 1.97, 95% CI: 1.31‒2.95). Subgroup analyses indicated that the association between LAP and gallstones was not affected by the stratification of the variables examined. Conclusion: Gallstones and LAP exhibited a positive association in our investigation, indicating that LAP may be utilized as a clinical indicator to determine the occurrence of gallstones. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis. [ABSTRACT FROM AUTHOR]

Obesity and type 2 diabetes mellitus are global public health issues. Although males show higher obesity and insulin resistance prevalence, current treatments often neglect sex-specific differences. White adipose tissue (WAT) is crucial in preventing lipotoxicity and inflammation and has become a key therapeutic target. Rosiglitazone (RSG), a potent PPARγ agonist, promotes healthy WAT growth and mitochondrial function through MitoNEET modulation. Recent RSG-based strategies specifically target white adipocytes, avoiding side effects. Our aim was to investigate whether sex-specific differences in the insulin-sensitizing effects of RSG exist on WAT during obesity and inflammation. We used Wistar rats of both sexes fed a high-fat diet (HFD, 22.5% fat content) for 16 weeks. Two weeks before sacrifice, a group of HFD-fed rats received RSG treatment (4 mg/kg of body weight per day) within the diet. HFD male rats showed greater insulin resistance, inflammation, mitochondrial dysfunction, and dyslipidemia than females. RSG had more pronounced effects in males, significantly improving insulin sensitivity, fat storage, mitochondrial function, and lipid handling in WAT while reducing ectopic fat deposition and enhancing adiponectin signaling in the liver. Our study suggests a significant sexual dimorphism in the anti-diabetic effects of RSG on WAT, correlating with the severity of metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Background: The relationship between healthy lifestyle and frailty remains unclear. Healthy weight is crucial for overall well-being, but using body mass index (BMI) to evaluate weight management is inefficient. This study clarifies the association between healthy lifestyle or its factors (non-smoking, moderate drinking, healthy weight, healthy diet, sufficeint physical activity, and non-sedentary) and frailty, and the feasibility of using the weight-adjusted waist index (WWI) reflecting central obesity as an intermediate indicator. Methods: This study included 4,473 participants from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). Healthy lifestyle quality was assessed by summing the scores of each healthy lifestyle factor. Frailty was assessed using a 49-item frailty index (FI), categorizing participants into robust, pre-frail, and frail. Logistic regression to investigate the association between healthy lifestyle or its factors, WWI, and frailty. Smooth curve fitting and threshold effect analyses were used to elucidate the nonlinear association. Subgroup and two other sensitivity analyses were conducted to confirm the stability of the results. A causal mediation model examined the proportion of frailty mediated by WWI. Results: The study identified 13.98% of the participants as frail. Optimal healthy lifestyle and frailty were negatively associated (OR: 0.39, 95%CI: 0.27–0.58). Five healthy lifestyle factors (non-smoking, healthy weight, healthy diet, sufficient physical activity, and non-sedentary) were associated with a lower prevalence of frailty, with odds ratios (OR) ranging from 0.48 to 0.61. We also analyzed the association between a healthy lifestyle and WWI (OR: 0.32, 95%CI: 0.27–0.37), WWI and frailty (OR: 1.85, 95%CI: 1.59–2.16). A positive association between WWI and FI was observed beyond the inflection point (9.99) (OR: 0.03, 95%CI: 0.02–0.03). Subgroup and sensitivity analyses confirmed stable associations between healthy lifestyle, WWI, and frailty. WWI partially mediated the association between a healthy lifestyle and frailty (mediating ratio = 20.50–20.65%). Conclusions: An optimal healthy lifestyle and positive healthy lifestyle factors are associated with a lower incidence of frailty. WWI may mediate the relationship between a healthy lifestyle and frailty. [ABSTRACT FROM AUTHOR]

Background: Podocyte injury is a common pathologic mechanism in diabetic kidney disease (DKD) and obesity-related glomerulopathy (ORG). Our previous study confirmed that Inonotus obliquus (IO) improved podocyte injury on DKD rats. The current study explored the pharmacological effects, related mechanisms and possible active components of IO on ORG mice. Methods: Firstly, by combining ultra-high performance liquid chromatography tandem mass spectrometry analysis (UPLC-Q-TOF-MS) with network pharmacology to construct the human protein-protein interaction mechanism and enrich the pathway, which led to discover the crucial mechanism of IO against ORG. Then, ORG mice were established by high-fat diet and biochemical assays, histopathology, and Western blot were used to explore the effects of IO on obesity and podocyte injury. Finally, network pharmacology-based findings were confirmed by immunohistochemistry. The compositions of IO absorbed in mice plasma were analyzed by UPLC-Q-TOF-MS and molecular docking was used to predict the possible active compounds. Results: The network pharmacology result suggested that IO alleviated the inflammatory response of ORG by modulating TNF signal. The 20-week in vivo experiment confirmed that IO improved glomerular hypertrophy, podocyte injury under electron microscopy, renal nephrin, synaptopodin, TNF-α and IL-6 expressions with Western blotting and immunohistochemical staining. Other indicators of ORG such as body weight, kidney weight, serum total cholesterol, liver triglyceride also improved by IO intervention. The components analysis showed that triterpenoids, including inoterpene F and trametenolic acid, might be the pharmacodynamic basis. Conclusion: The research based on UPLC-Q-TOF-MS analysis, network pharmacology and in vivo experiment suggested that the amelioration of IO on podocyte injury in ORG mice via its modulation on TNF signal. Triterpenoids were predicated as acting components. [ABSTRACT FROM AUTHOR]

The study aimed to identify predictors of 6 -month outcomes in acute ischemic stroke (AIS) patients using the modified Rankin Scale (mRS). A prospective observational cohort study was conducted on 277 AIS patients admitted to the Neurology Departments of Cluj-Napoca Emergency County Clinical Hospital between December 2020 and July 2021. After excluding those lost to follow-up or who withdrew due to COVID-19 concerns, 121 patients were followed for six months. Data collected included demographic details, clinical assessments (including NIHSS and mRS scores), laboratory tests, and imaging results. The study found significant differences between patients with mild/moderate disability (mRS 0-3) and those with severe disability (mRS 4-5) at six months. Age, heart failure, NIHSS score, resistin levels, C-reactive protein, and lesion volume were significantly associated with worse outcomes. Multivariate logistic regression revealed that heart failure was an independent predictor of severe disability, increasing the risk by over seven times. Specific clinical and biochemical markers at admission may be able to predict long-term functional outcomes in AIS patients, which may inform individualized patient management and rehabilitation strategies. [ABSTRACT FROM AUTHOR]

NAD+-dependent deacetylase sirtuin-1 (Sirt1) belongs to the sirtuins family, known to be longevity regulators, and exerts a key role in the prevention of vascular aging. By aging, the expression levels of Sirt1 decline with a severe impact on vascular function, such as the rise of endothelial dysfunction, which in turn promotes the development of cardiovascular diseases. In this context, the impact of Sirt1 activity in preventing endothelial senescence is particularly important. Given the key role of Sirt1 in counteracting endothelial senescence, great efforts have been made to deepen the knowledge about the intricate cross-talks and interactions of Sirt1 with other molecules, in order to set up possible strategies to boost Sirt1 activity to prevent or treat vascular aging. The aim of this review is to provide a proper background on the regulation and function of Sirt1 in the vascular endothelium and to discuss the recent advances regarding the therapeutic strategies of targeting Sirt1 to counteract vascular aging. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), a commonly used anticancer agent, causes cardiotoxicity that begins with the first dose and may progress to heart failure years after treatment. An inflammatory response associated with neutrophil recruitment has been recognized as a mechanism of DOX-induced cardiotoxicity. This study aimed to validate mRNA expression of the previously identified biomarkers of DOX-induced cardiotoxicity, PGLYRP1, CAMP, MMP9, and CEACAM8, and to assay their protein expression in the peripheral blood of breast cancer patients. Blood samples from 40 breast cancer patients treated with DOX-based chemotherapy were collected before and after the first chemotherapy cycle and > 2 years after treatment. The protein and gene expression of PGLYRP1/Tag7, CAMP/LL37, MMP9/gelatinase B, and CEACAM8/CD66b were determined using ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of each candidate biomarker. Patients with cardiotoxicity (n = 20) had significantly elevated levels of PGLYRP1, CAMP, MMP9, and CEACAM8 at baseline, after the first dose of DOX-based chemotherapy, and at > 2 years after treatment relative to patients without cardiotoxicity (n = 20). The first dose of DOX induced significantly higher levels of all examined biomarkers in both groups of patients. At > 2 years post treatment, the levels of all but MMP9 dropped below the baseline. There was a good correlation between the expression of mRNA and the target proteins. We demonstrate that circulating levels of PGLYRP1, CAMP, MMP9, and CEACAM8 can predict the cardiotoxicity of DOX. This novel finding may be of value in the early identification of patients at risk for cardiotoxicity. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory disease that may lead to dilated cardiomyopathy. Viral infection of the myocardium triggers immune responses, which involve, among others, macrophage infiltration, oxidative stress, expression of pro-inflammatory cytokines, and microRNAs (miRNAs). The cardioprotective role of estrogen in myocarditis is well documented; however, sex differences in the miRNA expression in chronic myocarditis are still poorly understood, and studying them further was the aim of the present study. Male and female ABY/SnJ mice were infected with CVB3. Twenty-eight days later, cardiac tissue from both infected and control mice was used for real-time PCR and Western blot analysis. NFκB, IL-6, iNOS, TNF-α, IL-1β, MCP-1, c-fos, and osteopontin (OPN) were used to examine the inflammatory state in the heart. Furthermore, the expression of several inflammation- and remodeling-related miRNAs was analyzed. NFκB, IL-6, TNF-α, IL-1β, iNOS, and MCP-1 were significantly upregulated in male mice with CVB3-induced chronic myocarditis, whereas OPN mRNA expression was increased only in females. Further analysis revealed downregulation of some anti-inflammatory miRNA in male hearts (let7a), with upregulation in female hearts (let7b). In addition, dysregulation of remodeling-related miRNAs (miR27b and mir199a) in a sex-dependent manner was observed. Taken together, the results of the present study suggest a sex-specific expression of pro-inflammatory markers as well as inflammation- and remodeling-related miRNAs, with a higher pro-inflammatory response in male CVB3 myocarditis mice. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is characterized by a steady decline in kidney function and affects roughly 10% of the world's population. This review focuses on the critical function of cyclic adenosine monophosphate (cAMP) signaling in CKD, specifically how it influences both protective and pathogenic processes in the kidney. cAMP, a critical secondary messenger, controls a variety of cellular functions, including transcription, metabolism, mitochondrial homeostasis, cell proliferation, and apoptosis. Its compartmentalization inside cellular microdomains ensures accurate signaling. In kidney physiology, cAMP is required for hormone-regulated activities, particularly in the collecting duct, where it promotes water reabsorption through vasopressin signaling. Several illnesses, including Fabry disease, renal cell carcinoma, nephrogenic diabetes insipidus, Bartter syndrome, Liddle syndrome, diabetic nephropathy, autosomal dominant polycystic kidney disease, and renal tubular acidosis, have been linked to dysfunction in the cAMP system. Both cAMP analogs and phosphodiesterase inhibitors have the potential to improve kidney function and reduce kidney damage. Future research should focus on developing targeted PDE inhibitors for the treatment of CKD. [ABSTRACT FROM AUTHOR]

Obesity is a global health crisis that is closely interrelated to many chronic diseases, such as cardiovascular disease and diabetes. This review provides an in-depth analysis of specific chemokines involved in the development of obesity, including C-C motif chemokine ligand 2 (CCL2), CCL3, CCL5, CCL7, C-X-C motif chemokine ligand 8 (CXCL8), CXCL9, CXCL10, CXCL14, and XCL1 (lymphotactin). These chemokines exacerbate the symptoms of obesity by either promoting the inflammatory response or by influencing metabolic pathways and recruiting immune cells. Additionally, the research highlights the positive effect of exercise on modulating chemokine expression in the obese state. Notably, it explores the potential effects of both aerobic exercises and combined aerobic and resistance training in lowering levels of inflammatory mediators, reducing insulin resistance, and improving metabolic health. These findings suggest new strategies for obesity intervention through the modulation of chemokine levels by exercise, providing fresh perspectives and directions for the treatment of obesity and future research. [ABSTRACT FROM AUTHOR]

Looking at the development status of Nigeria and other developing nations, most low-income and rural households often use coal as a source of energy which necessitates its trade very close to the communities. Moreover, the effects of exposure to coal mining activities are rarely explored or yet to be studied, not to mention the numerous street coal vendors in Nigeria. This study investigated the oxidative stress levels in serum and urine through the biomarker 8-OHdG and DNA damage via single cell gel electrophoresis (alkaline comet assay). Blood and urine levels of 8-OHdG from 130 coal vendors and 130 population-based controls were determined by ELISA. Alkaline comet assay was also performed on white blood cells for DNA damage. The average values of 8-OHdG in serum and urine of coal vendors were 22.82 and 16.03 ng/ml respectively, which were significantly greater than those detected in controls (p < 0.001; 15.46 and 10.40 ng/ml of 8-OHdG in serum and urine respectively). The average tail length, % DNA in tail and olive tail moment were 25.06 μm, 18.71% and 4.42 respectively for coal vendors. However, for controls, the average values were 4.72 μm, 3.63% and 1.50 for tail length, % DNA in tail and olive tail moment respectively which were much lower than coal vendors (p < 0.001). Therefore, prolonged exposure to coal dusts could lead to higher serum and urinary 8-OHdG and significant DNA damage in coal vendors observed in tail length, % DNA in tail, and olive tail moment by single cell gel electrophoresis. It is therefore established that coal vendors exhibit a huge risk from oxidative stress and assessment of 8-OHdG with single cell gel electrophoresis has proven to be a feasible tool as biomarkers of DNA damage. [ABSTRACT FROM AUTHOR]

Background and Objectives: Acute ischemic stroke (AIS) is a leading cause of death and disability with poor long-term outcomes. Creating a predictive score for long-term mortality in AIS might be important for optimizing treatment strategies. The aim of this study is to develop and validate a predictive score for three-year mortality in patients with AIS using several demographic, clinical, laboratory and imaging parameters. Materials and Methods: This study included 244 AIS patients admitted to a tertiary center and followed up for three years. The patients' data included demographics, clinical features, laboratory tests (including resistin and leptin levels) and imaging parameters. The patients were randomly divided into a predictive group (n = 164) and a validation group (n = 80). Results: Advanced age, a high NIHSS score, low levels of hemoglobin, elevated resistin levels and the presence of carotid plaques were independently associated with three-year mortality. The predictive model incorporated these variables, and it was validated in a separate cohort. Leptin levels did not significantly predict mortality. Conclusions: This study developed and validated a promising predictive score for three-year mortality in patients with AIS. Advanced age, high NIHSS scores, low hemoglobin levels, elevated resistin levels and the presence of carotid plaques were the independent predictors of long-term mortality. [ABSTRACT FROM AUTHOR]

Background: The global prevalence of obesity has escalated into a formidable health challenge intricately linked with the risk of developing cardiac diastolic disfunction and heart failure with preserved ejection fraction (HFpEF). Abnormal fat distribution is potentially strongly associated with an increased risk of cardiac diastolic dysfunction, and we aimed to scrutinize and elucidate the correlation between them. Methods: Following the Cochrane Handbook and PRISMA 2020 guidelines, we systematically reviewed the literature from PubMed, Embase, and Web of Science. We focused on studies reporting the mean and standard deviation (SD) of abnormal fat in HFpEF or cardiac diastolic dysfunction patients and the Pearson/Spearman correlation coefficients for the relationship between abnormal fat distribution and the risk of developing cardiac diastolic dysfunction. Data were standardized to the standard mean difference (SMD) and Fisher's z value for meta-analysis. Results: After progressive filtering and selection, 63 studies (43,113 participants) were included in the quantitative analyses. Abnormal fat distribution was significantly greater in participants with cardiac diastolic dysfunction than in controls [SMD 0.88 (0.69, 1.08)], especially in epicardial adipose tissue [SMD 0.99 (0.73, 1.25)]. Abnormal fat distribution was significantly correlated with the risk of developing cardiac diastolic dysfunction [E/E': 0.23 (0.18, 0.27), global longitudinal strain: r=-0.11 (-0.24, 0.02)]. Meta-regression revealed sample size as a potential heterogeneous source, and subgroup analyses revealed a stronger association between abnormal fat distribution and the risk of developing cardiac diastolic dysfunction in the overweight and obese population. Conclusion: Abnormal fat distribution was significantly associated with the risk of developing cardiac diastolic dysfunction. Trial registration: CRD42024543774. [ABSTRACT FROM AUTHOR]

Despite efforts to elucidate the cellular adaptations induced by obesity, cellular bioenergetics is currently considered a crucial target. New strategies to delay the onset of the hazardous adaptations induced by obesity are needed. Therefore, we evaluated the effects of 4 weeks of melatonin treatment on mitochondrial function and lipid metabolism in the livers of leptin-deficient mice. Our results revealed that the absence of leptin increased lipid storage in the liver and induced significant mitochondrial alterations, which were ultimately responsible for defective ATP production and reactive oxygen species overproduction. Moreover, leptin deficiency promoted mitochondrial biogenesis, fusion, and outer membrane permeabilization. Melatonin treatment reduced the bioenergetic deficit found in ob/ob mice, alleviating some mitochondrial alterations in the electron transport chain machinery, biogenesis, dynamics, respiration, ATP production, and mitochondrial outer membrane permeabilization. Given the role of melatonin in maintaining mitochondrial homeostasis, it could be used as a therapeutic agent against adipogenic steatosis. [ABSTRACT FROM AUTHOR]

Obesity is an epidemic worldwide. Overweight and multiple obesity-related mechanisms, including dysmetabolic alterations, contribute to cardiovascular deleterious effects. Hence, overweight and obesity have been independently associated with increased cardiovascular risk, whose assessment is crucial for preserving life quality and reducing mortality, and to address appropriate therapeutic strategies in obese patients. Beyond the standard of care in managing overweight and obesity in adults (i.e., diet and physical exercise), several relevant pharmacotherapies have been approved, and several procedures and device types for weight loss have been recommended. In such a contest, medical weight management remains one option for treating excess weight. Most drugs used for obesity reduce appetite and increase satiety and, secondarily, slow gastric emptying to reduce body weight and, therefore, act also to improve metabolic parameters. In this contest, agonists of the glucagon-like peptide-1 receptor (GLP-1RAs) modulate different metabolic pathways associated with glucose metabolism, energy homeostasis, antioxidation, and inflammation. Moreover, this class of drugs has shown efficacy in improving glycemic control, reducing the incidence of cardiovascular events in type 2 diabetic patients, and reducing body weight independently of the presence of diabetes. Recently, in overweight or obese patients with pre-existing cardiovascular disease but without diabetes, the GLP-1RA semaglutide reduced the incidence of cardiovascular and cerebrovascular events and death from cardiovascular causes. Thus, semaglutide has been approved for secondary prevention in obese people with cardiovascular disease. Nevertheless, whether this class of drugs is equally effective for primary prevention in obese people has to be demonstrated. In this review, we will summarize updates on the pathophysiology of obesity, the effects of obesity on cardiovascular risk, the impact of different obesity phenotypes on cardiovascular diseases, and the novelties in the clinical management of obesity for cardiovascular prevention. [ABSTRACT FROM AUTHOR]

Background: As a novel biomarker for cardiovascular diseases, epicardial adipose tissue (EAT) has been linked to psoriasis. We conducted an updated systematic review, building upon a previous report on the relationship between EAT and psoriasis. Methods: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials. The methodological quality of each study was assessed using the Newcastle–Ottawa Scale. The pooled mean difference (MD) or standardized mean difference (SMD) and the corresponding confidence interval (CIs) were calculated. Results: We included 10 studies with 1287 participants. Five of the included studies were of high methodological quality, while the other five were of moderate quality. The pooled data indicated that psoriasis patients had significantly increased EAT compared to individuals in the control group (SMD 1.53, 95% CI 0.61 to 2.45, 9 studies, 1195 participants). The subgroup analysis showed that psoriasis patients had significantly increased EAT thickness compared with the controls (SMD 2.45, 95% CI 0.73 to 4.17, 5 studies, 657 participants). Similarly, EAT area in single-slice CT images was significantly higher in the psoriasis group than in the control group (SMD 0.45, 95% CI 0.14 to 0.76, 2 studies, 195 participants). The EAT volume based on CT images appeared to be higher in the psoriasis group than in the control group, but the difference was not statistically significant (SMD 0.32, 95% CI −0.06 to 0.70, 2 studies, 343 participants). Conclusions: EAT, especially echocardiographic EAT thickness and CT-determined EAT area, was significantly associated with psoriasis, but CT-determined EAT volume was not. [ABSTRACT FROM AUTHOR]

Insulin signaling is vital for regulating cellular metabolism, growth, and survival pathways, particularly in tissues such as adipose, skeletal muscle, liver, and brain. Its role in the heart, however, is less well-explored. The heart, requiring significant ATP to fuel its contractile machinery, relies on insulin signaling to manage myocardial substrate supply and directly affect cardiac muscle metabolism. This review investigates the insulin–heart axis, focusing on insulin's multifaceted influence on cardiac function, from metabolic regulation to the development of physiological cardiac hypertrophy. A central theme of this review is the pathophysiology of insulin resistance and its profound implications for cardiac health. We discuss the intricate molecular mechanisms by which insulin signaling modulates glucose and fatty acid metabolism in cardiomyocytes, emphasizing its pivotal role in maintaining cardiac energy homeostasis. Insulin resistance disrupts these processes, leading to significant cardiac metabolic disturbances, autonomic dysfunction, subcellular signaling abnormalities, and activation of the renin–angiotensin–aldosterone system. These factors collectively contribute to the progression of diabetic cardiomyopathy and other cardiovascular diseases. Insulin resistance is linked to hypertrophy, fibrosis, diastolic dysfunction, and systolic heart failure, exacerbating the risk of coronary artery disease and heart failure. Understanding the insulin–heart axis is crucial for developing therapeutic strategies to mitigate the cardiovascular complications associated with insulin resistance and diabetes. [ABSTRACT FROM AUTHOR]

Peritoneal washing cytology (CY) in patients with pancreatic cancer is mainly used for staging; however, it may also be used to evaluate the intraperitoneal status to predict a more accurate prognosis. Here, we investigated the potential of deep learning of CY specimen images for predicting the 1-year prognosis of pancreatic cancer in CY-positive patients. CY specimens from 88 patients with prognostic information were retrospectively analyzed. CY specimens scanned by the whole slide imaging device were segmented and subjected to deep learning with a Vision Transformer (ViT) and a Convolutional Neural Network (CNN). The results indicated that ViT and CNN predicted the 1-year prognosis from scanned images with accuracies of 0.8056 and 0.8009 in the area under the curve of the receiver operating characteristic curves, respectively. Patients predicted to survive 1 year or more by ViT showed significantly longer survivals by Kaplan–Meier analyses. The cell nuclei found to have a negative prognostic impact by ViT appeared to be neutrophils. Our results indicate that AI-mediated analysis of CY specimens can successfully predict the 1-year prognosis of patients with pancreatic cancer positive for CY. Intraperitoneal neutrophils may be a novel prognostic marker and therapeutic target for CY-positive patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Ischemic heart disease, manifesting as myocardial infarction (MI), remains the leading cause of death in the western world. Both ischemia and reperfusion (I/R) cause myocardial injury and result in cardiac inflammatory responses. This sterile inflammation in the myocardium consists of multiple phases, involving cell death, tissue remodeling, healing, and scar formation, modulated by various cytokines, including the macrophage migration inhibitory factor (MIF). Meanwhile, different immune cells participate in these phases, with myeloid cells acting as first responders. They migrate to the injured myocardium and regulate the initial phase of inflammation. The MIF modulates the acute inflammatory response by affecting the metabolic profile and activity of myeloid cells. This review summarizes the role of the MIF in regulating myeloid cell subsets in MI and I/R injury and discusses emerging evidence of metabolism-directed cellular inflammatory responses. Based on the multifaceted role of the MIF affecting myeloid cells in MI or I/R, the MIF can be a therapeutic target to achieve metabolic balance under pathology and alleviate inflammation in the heart. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease increasing cardiovascular disease (CVD) morbidity and mortality. Autoantibodies against apolipoprotein A-1 (AAA-1) are a possible novel CVD risk factor promoting inflammation and disrupting cellular lipid homeostasis, two prominent pathogenic features of NAFLD. We explored the role of AAA-1 in NAFLD and their association with CVD risk., Methods: HepaRG cells and liver sections from ApoE-/- mice exposed to AAA-1 were used for lipid quantification and conditional protein expression. Randomly selected sera from 312 subjects of the Prevention of Renal and Vascular End-stage Disease (PREVEND) general population cohort were used to measure AAA-1. A Fatty Liver Index (FLI) ≥ 60 and a 10-year Framingham Risk Score (FRS) ≥ 20% were used as proxy of NAFLD and high CVD risk, respectively., Results: In-vitro and mouse models showed that AAA-1 increased triglyceride synthesis leading to steatosis, and promoted inflammation and hepatocyte injury. In the 112 PREVEND participants with FLI ≥ 60, AAA-1 were associated with higher FRS, alkaline phosphatase levels, lower HDL cholesterol and tended to display higher FLI values. Univariate linear and logistic regression analyses (LRA) confirmed significant associations between AAA-1, FLI and FRS ≥ 20%, while in adjusted LRA, FLI was the sole independent predictor of FRS ≥ 20% (OR: 1.05, 95%CI 1.01-1.09, P = 0.003). AAA-1 was not an independent FLI predictor., Conclusions: AAA-1 induce a NAFLD-compatible phenotype in vitro and in mice. Intricate associations exist between AAA-1, CVD risk and FLI in the general population. Further work is required to refine the role of AAA-1 in NAFLD and to determine if the AAA-1 association with CVD is affected by hepatic steatosis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Obesity epidemic reached the dimensions of a real global health crisis with more than one billion people worldwide living with obesity. Multiple obesity-related mechanisms cause structural, functional, humoral, and hemodynamic alterations with cardiovascular (CV) deleterious effects. A correct assessment of the cardiovascular risk in people with obesity is critical for reducing mortality and preserving quality of life. The correct identification of the obesity status remains difficult as recent evidence suggest that different phenotypes of obesity exist, each one associated with different degrees of CV risk. Diagnosis of obesity cannot depend only on anthropometric parameters but should include a precise assessment of the metabolic status. Recently, the World Heart Federation and World Obesity Federation provided an action plan for management of obesity-related CV risk and mortality, stressing for the instauration of comprehensive structured programs encompassing multidisciplinary teams. In this review we aim at providing an updated summary regarding the different obesity phenotypes, their specific effects on CV risk and differences in clinical management., (© 2023. The Author(s).)

Objective: Previous studies investigated the effect of pericardial fat on cardiovascular diseases. However, until now there was no systematic review and meta-analysis investigated this association, thus we conducted this article to assess the relationship between pericardial fat and cardiovascular diseases., Methods: We searched PubMed, The Cochrane Library, Scopus, Google Scholar and Clinicaltrials.gov to select observational studies reported the relationship between pericardial fat and cardiovascular diseases including coronary artery disease (CAD), ventricular dysfunction, heart failure (HF), atrial fibrillation (AF), major adverse cardiac events (MACE), coronary artery calcifications (CAC), arrhythmias other than atrial fibrillation, and cardiovascular events prediction scores. Meta XL 5.3 was used for data analysis., Results: A total of 83 articles that included 73,934 patients were included in our analysis. The results showed that pericardial fat was significantly associated with CAD (OR = 1.38; 95% CI: 1.28-1.50), ventricular dysfunction (OR = 1.53 per 1 mm 3 ; 95% CI: 1.17-2.01), HF (OR = 1.32 per 1 mm 3 ; 95% CI: 1.23-1.41), AF (OR = 1.16 per 1 mm 3 ; 95% CI: 1.09-1.24), MACE (OR = 1.39 per 1 mm 3 ; 95% CI: 1.22-1.57), and CAC (OR = 1.15 per 1 mm 3 ; 95% CI: 1.05-1.27). On the other hand, there was no enough data about the relationship between pericardial fat with arrhythmias other than atrial fibrillation or cardiovascular risk scores., Conclusion: The analysis demonstrated that the relationship between pericardial fat volume and cardiovascular diseases was significant. Since pericardial fat is a good predictor of obesity, it suggests investigating its relationship and adds on effect to previously established risk factor to evaluate the possibility of incorporating it with cardiovascular risk scores., (© 2023 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most common liver disorder worldwide, with an estimated global prevalence of more than 31%. Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a progressive form of MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide a comprehensive analysis of the extrahepatic manifestations of MASH, focusing on chronic diseases related to the cardiovascular, muscular, and renal systems. A systematic review of published studies and literature was conducted to summarize the findings related to the systemic impacts of MASLD and MASH. The review focused on the association of MASLD and MASH with metabolic comorbidities, cardiovascular mortality, sarcopenia, and chronic kidney disease. Mechanistic insights into the concept of lipotoxic inflammatory "spill over" from the MASH-affected liver were also explored. MASLD and MASH are highly associated (50%-80%) with other metabolic comorbidities such as impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, and hypertension. Furthermore, more than 90% of obese patients with type 2 diabetes have MASH. Data suggest that in middle-aged individuals (especially those aged 45-54), MASLD is an independent risk factor for cardiovascular mortality, sarcopenia, and chronic kidney disease. The concept of lipotoxic inflammatory "spill over" from the MASH-affected liver plays a crucial role in mediating the systemic pathological effects observed. Understanding the multifaceted impact of MASH on the heart, muscle, and kidney is crucial for early detection and risk stratification. This knowledge is also timely for implementing comprehensive disease management strategies addressing multiorgan involvement in MASH pathogenesis. [ABSTRACT FROM AUTHOR]

Background. Type 2 diabetes is a condition in which the body becomes resistant to the effects of insulin, leading to reduced insulin production in the pancreas. It has genetic‐ and family‐related risk factors that cannot be changed, along with modifiable lifestyle factors. The precise genetic causes of type 2 diabetes are still unknown. However, individuals can potentially slow or stop the progression of the condition by making dietary adjustments and increasing physical activity levels. Material and Methods. Forty‐five type II diabetic patients in the study included participants between 40 and 60 years old, with a minimum duration of one year, as well as 45 healthy control subjects who were matched in terms of age and sex, and had no underlying systemic diseases. Oral examination is done for the symptoms including burning sensation, candidiasis, and a reduction in the production of saliva. The rate of saliva flow (in milliliters per minute) was measured in samples of saliva that were not stimulated. The salivary trace elements and levels of adipocytokines were evaluated using colorimetric and Ethylenediaminetetraacetic acid (ELISA) testing. The quantification of Candida colony numbers, an enrichment and culture approach, was used to achieve a concentration of 100,000 colony‐forming units per milliliter (CFU/ml). The ShowNovo WG1 halimeter was used to measure volatile sulfur compounds in breath. The salivary glucose oxidase assay was conducted using a colorimetric technique, while the determination of trace elements was also performed using a colorimetric assay method. Result. The diabetic group exhibited a significant increase in the number of Candida spp colonies due to elevated levels of glucose in the saliva (p > 0.05). However, the variables being examined, such as body mass index (BMI), burning mouth syndrome (BMS), salivary flow rate (SFR), salivary leptin, salivary copper, and salivary magnesium, did not exhibit any significant variations in quantities between the diabetic and healthy groups (p > 0.05). Conclusion. The data collected in this research aid in the creation of a preventative program for oral fungal infections in individuals with type 2 diabetes. The program utilizes saliva and its constituents. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the effects of High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) on weight, body composition, blood lipid indicators, and metabolic status in college students living with obesity. The study focused on a sample of 40 college students living with obesity, including 20 males and 20 females, aged between 18 and 25. Participants were randomly assigned to either the HIIT group or the MICT group. Both groups underwent an 8-week intervention, consisting of three sessions per week with alternate-day training. The MICT group's training consisted of continuous aerobic exercise for 35 min at 60–70% of maximum heart rate. The HIIT group engaged in 28 min of alternating high-intensity and low-intensity exercise, where the high-intensity phase was at 85–90% of maximum heart rate for 4 min, followed by a 3-min recovery period at 50–60% of maximum heart rate, repeated four times. Both groups underwent heart rate monitoring before and after the training sessions to ensure the accuracy of the training intensity. Within each group, further distinctions were made based on gender, resulting in the following subgroups: Male HIIT group (n = 10), Female HIIT group (n = 10), Male MICT group (n = 10), and Female MICT group (n = 10). Differences in anthropometric and biochemical indicators among the groups were analyzed, and the different effects of the two intervention strategies on the obese college student population were comprehensively evaluated. Compared to the baseline assessment, the HIIT group showed a more favorable declining trend than the MICT group in terms of body morphology and body composition, particularly in the aspect of body fat percentage (BF%). The male HIIT group, female HIIT group, male MICT group, and female MICT group respectively reduced by − 23.71%, − 26.76%, − 9.81%, − 7.16%. Male and female HIIT group experienced a more pronounced decrease compared to the MICT group, with the female HIIT group reducing an additional 3.75% more than the male HIIT group. Regarding intergroup differences, BF% significant differences were shown between male MICT group and the HIIT group (P < 0.05), and female MICT group and the HIIT group (P < 0.01). In terms of biochemical indicators, the HIIT group also presented a more favorable declining trend compared to the MICT group, with male HIIT participants showing more reduction than female HIIT participants, especially in total cholesterol (TC) (10.64%), low-density lipoprotein cholesterol (LDL-C) (11.73%), alanine aminotransferase (ALT) (11.99%), and uric acid (UA) (11.76%). Regarding triglycerides (TG), significant intergroup differences were observed between male MICT and HIIT groups (P < 0.01) and female MICT and HIIT groups (P < 0.01). Concerning ALT, a significant difference was shown between female MICT and HIIT groups (P < 0.01), while no significant difference was observed among male participants. Overall, for college students living with obesity, both HIIT and MICT have shown positive effects. Among these, HIIT demonstrates greater effectiveness compared to MICT in BF% and biochemical markers. [ABSTRACT FROM AUTHOR]

Background and purpose: Malignant cerebral edema (MCE) is one of serious complications with high mortality following endovascular treatment (EVT) for acute ischemic stroke (AIS) with large vessel occlusion. We aimed to investigate the relationship between postoperative neutrophil-to-lymphocyte ratio (NLR) and MCE after EVT. Methods: The clinical and imaging data of 175 patients with AIS of anterior circulation after EVT were studied. Admission and postoperative NLR were determined. The presence of MCE was evaluated on the computed tomography performed 24  h following EVT. The clinical outcomes were measured using the modified Rankin Scale (mRS) at 90-day after onset. Univariate and multivariate regression analyses were used to analyze the relationship between postoperative NLR and MCE. Optimal cutoff values of postoperative NLR to predict MCE were defined using receiver operating characteristic analysis. Results: MCE was observed in 24% of the patients who underwent EVT and was associated with a lower rate of favorable clinical outcomes at 90-day. Multivariate logistic regression analysis demonstrated that baseline Alberta Stroke Program Early CT Score (ASPECT) score (OR  =  0.614, 95% CI 0.502–0.750, p  =  0.001), serum glucose (OR  =  1.181, 95% CI 1.015–1.374, p  =  0.031), and postoperative NLR (OR  =  1.043, 95% CI 1.002–1.086, p  =  0.041) were independently associated with MCE following EVT for AIS with large vessel occlusion. Postoperative NLR had an area under the receiver operating characteristic curve of 0.743 for prediction MCE, and the optimal cutoff value was 6.15, with a sensitivity and specificity of 86.8% and 55%. Conclusion: Elevated postoperative NLR is independently associated with malignant brain edema following EVT for AIS with large vessel occlusion, and may serve as an early predictive indicator for MCE after EVT. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease (ASCVD) has become the leading cause of death worldwide, and early diagnosis and treatment of atherosclerosis (AS) are crucial for reducing the occurrence of acute cardiovascular events. However, early diagnosis of AS is challenging, and oral anti‐AS drugs suffer from limitations like imprecise targeting and low bioavailability. To overcome the aforementioned shortcomings, Cur/MOF@DS is developed, a nanoplatform integrating diagnosis and treatment by loading curcumin (Cur) into metal−organic frameworks with nanozymes and magnetic resonance imaging (MRI) properties. In addition, the surface‐modification of dextran sulfate (DS) enables PCN‐222(Mn) effectively target scavenger receptor class A in macrophages or foam cells within the plaque region. This nanoplatform employs mechanisms that effectively scavenge excessive reactive oxygen species in the plaque microenvironment, promote macrophage autophagy and regulate macrophage polarization to realize lipid regulation. In vivo and in vitro experiments confirm that this nanoplatform has outstanding MRI performance and anti‐AS effects, which may provide a new option for early diagnosis and treatment of AS. [ABSTRACT FROM AUTHOR]

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC. Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, and TIMER database, were employed to assess the diagnostic and prognostic value of FAM20A in LUSC. These tools also helped evaluate immune cell infiltration, immune checkpoint genes, DNA repair-related genes, DNA methylation, and tumor-related pathways. Results: FAM20A expression was found to be significantly reduced in LUSC, correlating with lower survival rates. It exhibited a negative correlation with key proteins in DNA repair signaling pathways, potentially contributing to LUSC's radiotherapy resistance. Additionally, FAM20A showed a positive correlation with immune checkpoints like CTLA-4, indicating potential heightened sensitivity to immunotherapies targeting these checkpoints. Conclusion: FAM20A emerges as a promising diagnostic and prognostic biomarker for LUSC, offering potential clinical applications. [ABSTRACT FROM AUTHOR]

This publication presents the effect of hypochlorous acid dry mist as a disinfectant on selected bacteria, viruses, spores, and fungi as well as on portable Microlife OXY 300 finger pulse oximeters and electronic systems of Raspberry Pi Zero microcomputers. The impact of hypochlorous acid on microbiological agents was assessed at concentrations of 300, 500, and 2000 ppm of HClO according to PN-EN 17272 (Variant I). Studies of the impact of hypochlorous acid fog on electronic components were carried out in an aerosol chamber at concentrations of 500 ppm and 2000 ppm according to two models consisting of 30 (Variant II) and 90 fogging cycles (Variant III). Each cycle included the process of generating a dry mist of hypochlorous acid (25 mL/m3), decontamination of the test elements, as well as cleaning the chamber of the disinfectant agent. The exposure of the materials examined on hypochlorous acid dry mist in all variants resulted in a decrease in the number of viruses, bacteria, spores, and fungi tested. In addition, the research showed that in the variants of hypochlorous acid fogging cycles analyzed, no changes in performance parameters and no penetration of dry fog of hypochlorous acid into the interior of the tested medical devices and electronic systems were observed. [ABSTRACT FROM AUTHOR]

Background: The identification of clinical factors affecting the gray-scale median (GSM) and determination of GSM diagnostic utility for differentiating between symptomatic and asymptomatic internal carotid artery (ICA) stenosis. Methods: This study included 45 patients with asymptomatic and 40 patients with symptomatic ICA stenosis undergoing carotid endarterectomy (CEA). Echolucency of carotid plaque was determined using computerized techniques for the GSM analysis. Study groups were compared in terms of clinical risk factors, coexisting comorbidities, and used pharmacotherapy. Results: Mean GSM values in the symptomatic group were significantly lower than in the asymptomatic group (p < 0.001). Both in the univariate as well as in the multiple regression analysis, GSM was significantly correlated with D-dimers and fasting plasma glucose levels and tended to correlate with β-adrenoceptor antagonist use in the symptomatic group. In asymptomatic patients, GSM was associated with the presence of grade 2 and grade 3 hypertension, and tended to correlate with the use of metformin, sulfonylureas, and statin. Independent factors for GSM in this group remained as grade 3 hypertension and statin's therapy. The receiver operating characteristic (ROC) analysis revealed that GSM differentiated symptomatic from asymptomatic ICA stenosis with sensitivity and specificity of 73% and 80%, respectively. Conclusion: The completely diverse clinical parameters may affect GSM in symptomatic and asymptomatic patients undergoing CEA, whose clinical characteristics were similar in terms of most of the compared parameters. GSM may be a clinically useful parameter for differentiating between symptomatic and asymptomatic ICA stenosis. [ABSTRACT FROM AUTHOR]

ASD is a complex condition primarily rooted in genetics, although influenced by environmental, prenatal, and perinatal risk factors, ultimately leading to genetic and epigenetic alterations. These mechanisms may manifest as inflammatory, oxidative stress, hypoxic, or ischemic damage. To elucidate potential variances in gene expression in ASD, a transcriptome analysis of peripheral blood mononuclear cells was conducted via RNA-seq on 12 ASD patients and 13 healthy controls, all of Sicilian ancestry to minimize environmental confounds. A total of 733 different statistically significant genes were identified between the two cohorts. Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) terms were employed to explore the pathways influenced by differentially expressed mRNAs. GSEA revealed GO pathways strongly associated with ASD, namely the GO Biological Process term "Response to Oxygen-Containing Compound". Additionally, the GO Cellular Component pathway "Mitochondrion" stood out among other pathways, with differentially expressed genes predominantly affiliated with this specific pathway, implicating the involvement of different mitochondrial functions in ASD. Among the differentially expressed genes, FPR2 was particularly highlighted, belonging to three GO pathways. FPR2 can modulate pro-inflammatory responses, with its intracellular cascades triggering the activation of several kinases, thus suggesting its potential utility as a biomarker of pro-inflammatory processes in ASD. [ABSTRACT FROM AUTHOR]

Background: The weight-adjusted waist index (WWI) is a recently developed obesity metric, and the aim of this study was to investigate the relationship between physical activity (PA) and WWI and the homeostasis model assessment of insulin resistance (HOMA-IR) in adolescents, as well as the joint association of HOMA-IR. Methods: This study was based on the National Health and Nutrition Survey conducted between 2013 and 2016 and included 1024 adolescents whose median age was 15.4. Multivariate linear regression was used to examine the associations between HOMA-IR and PA and WWI. Using generalized additive models, a potential nonlinear link between WWI and HOMA-IR was evaluated. Subgroup analysis was also carried out. Results: The fully adjusted model revealed a positive association (β: 0.48, 95% CI: 0.43, 0.53) between the WWI and HOMA-IR. The HOMA-IR was lower in physically active (β: -0.16, 95% CI: -0.26, -0.05) participants versus inactive participants. Participants who had higher WWI and were not physically active (β: 0.69; 95% CI: 0.56, 0.82) had the highest levels of HOMA-IR compared to participants who had lower WWI and were physically active. Subgroup analysis revealed that these correlations were similar in males and females. Conclusion: Our results demonstrated that higher WWI and PA were associated with a lower HOMA-IR and that WWI and PA had a combined association with HOMA-IR. The findings of this study are informative for the preventing insulin resistance in adolescents. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a multifactorial condition that significantly increases the risk of cardiovascular disease and chronic kidney disease (CKD). Recent studies have emphasized the role of lipid dysregulation in activating cellular mechanisms that contribute to CKD progression in the context of MetS. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated efficacy in improving various components of MetS, including obesity, dyslipidemia, and insulin resistance. While SGLT2i have shown cardioprotective benefits, the underlying cellular mechanisms in MetS and CKD remain poorly studied. Therefore, this review aims to elucidate the cellular mechanisms by which SGLT2i modulate lipid metabolism and their impact on insulin resistance, mitochondrial dysfunction, oxidative stress, and CKD progression. We also explore the potential benefits of combining SGLT2i with other antidiabetic drugs. By examining the beneficial effects, molecular targets, and cytoprotective mechanisms of both natural and synthetic SGLT2i, this review provides a comprehensive understanding of their therapeutic potential in managing MetS-induced CKD. The information presented here highlights the significance of SGLT2i in addressing the complex interplay between metabolic dysregulation, lipid metabolism dysfunction, and renal impairment, offering clinicians and researchers a valuable resource for developing improved treatment strategies and personalized approaches for patients with MetS and CKD. [ABSTRACT FROM AUTHOR]

Annexin A2 (ANXA2) is a multifunctional calcium- and phospholipid-binding protein that plays an important role in various cells. During pathogen infections, ANXA2 modulates the nuclear factor kappa-B (NF-κB) and cell apoptosis signaling pathways and guides the chemotaxis of inflammatory cells toward inflammation sites, thereby protecting the host organism through the modulation of the inflammatory response. In addition, ANXA2 can regulate immune responses, and in certain pathogen infections, it can interact with pathogen proteins to facilitate their invasion and proliferation. This review provides an overview of the research progress on how ANXA2 regulates pathogen infections. [ABSTRACT FROM AUTHOR]

Obesity is an important condition affecting the quality of life of numerous patients and increasing their associated risk for multiple diseases, including tumors and immune-mediated disorders. Inflammation appears to play a major role in the development of obesity and represents a central point for the activity of cellular and humoral components in the adipose tissue. Macrophages play a key role as the main cellular component of the adipose tissue regulating the chronic inflammation and modulating the secretion and differentiation of various pro- and anti-inflammatory cytokines. Inflammation also involves a series of signaling pathways that might represent the focus for new therapies and interventions. Weight loss is essential in decreasing cardiometabolic risks and the degree of associated inflammation; however, the latter can persist for long after the excess weight is lost, and can involve changes in macrophage phenotypes that can ensure the metabolic adjustment. A clear understanding of the pathophysiological processes in the adipose tissue and the interplay between obesity and chronic inflammation can lead to a better understanding of the development of comorbidities and may ensure future targets for the treatment of obesity. [ABSTRACT FROM AUTHOR]

Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke is more common. However, there is still a lack of effective methods to improve the prognosis and reduce the incidence of its complications. At present, there is evidence that peripheral organs are involved in the inflammatory response after stroke. Moreover, the interaction between central and peripheral inflammation includes the activation of resident and peripheral immune cells, as well as the activation of inflammation-related signaling pathways, which all play an important role in the pathophysiology of stroke. In this review, we discuss the mechanisms of inflammatory response after ischemic stroke, as well as the interactions through circulatory pathways between peripheral organs (such as the gut, heart, lung and spleen) and the brain to mediate and regulate inflammation after ischemic stroke. We also propose the potential role of meningeal lymphatic vessels (MLVs)-cervical lymph nodes (CLNs) as a brain-peripheral crosstalk lymphatic pathway in ischemic stroke. In addition, we also summarize the mechanisms of anti-inflammatory drugs in the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: This study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the older population. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we further explored the potential mediating effect of inflammation within these associations. Methods: A cohort of 3029 participants aged over 65 years old, spanning six NHANES cycles from 2005 to 2016, was enrolled and assessed. The primary endpoints of the study included all-cause mortality and cardiovascular mortality utilizing data from National Center for Health Statistics (NCHS). Cox regression model and subgroup analysis were conducted to assess the associations of CMI with all-cause and cardiovascular mortality. The mediating effect of inflammation-related indicators including leukocyte, neutrophil, lymphocyte, systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) were evaluated to investigate the potential mechanism of the associations between CMI and mortality through mediation package in R 4.2.2. Results: The mean CMI among the enrolled participants was 0.74±0.66, with an average age of 73.28±5.50 years. After an average follow-up period of 89.20 months, there were 1,015 instances of all-cause deaths and 348 cardiovascular deaths documented. In the multivariable-adjusted model, CMI was positively related to all-cause mortality (Hazard Ratio (HR)=1.11, 95% CI=1.01-1.21). Mediation analysis indicated that leukocytes and neutrophils mediated 6.6% and 13.9% of the association of CMI with all-cause mortality. Conclusion: Elevated CMI is positively associated with all-cause mortality in the older adults. The association appeared to be partially mediated through inflammatory pathways, indicating that CMI may serve as a valuable indicator for poor prognosis among the older population. [ABSTRACT FROM AUTHOR]