Systemic Inflammatory State Research Articles

The Association Between Periodontitis and Respiratory Diseases: A Comprehensive Review

Periodontal disease is a significant factor in periodontal destruction, primarily initiated by a multi-bacterial infection that progresses through a cascade of chronic inflammatory responses. This persistent inflammation not only affects periodontal tissues but also has systemic implications, heightening the risk of various systemic diseases. Among these, respiratory diseases—which are closely linked to inflammatory processes, are of particular concern. Conditions such as asthma, pneumonia, chronic obstructive pulmonary disease (COPD), and lung cancer have been increasingly associated with the chronic inflammatory state induced by periodontitis. The aim of this review was to elucidate the mechanisms underlying the association between periodontitis and respiratory diseases. Chronic periodontitis creates a state of systemic inflammation that can disseminate through the bloodstream, impacting distant organs, including the lungs. Emerging evidence from recent studies highlights the role of periodontitis in both the initiation and exacerbation of respiratory diseases. Microbial pathogens associated with periodontitis, such as Porphyromonas gingivalis, can be aspirated into the lower respiratory tract, leading to either direct infection or modulation of the local immune response. This can increase susceptibility to respiratory conditions such as pneumonia and exacerbate pre-existing diseases like COPD and asthma. In summary, the relationship between periodontitis and respiratory diseases is complex and multifaceted, involving direct microbial interactions, systemic inflammation, and immune modulation. Understanding these connections is crucial for developing integrated therapeutic strategies that address both oral and respiratory health.

High neutrophil-to-lymphocyte ratio at Helicobacter pylori eradication increases the risk of eradication failure and post-eradication gastric cancer

Introduction Vonoprazan has been known to have a high Helicobacter pylori (H. pylori) eradication rate since its launch in 2015. Yet, the risk factors for eradication failure and development of post-eradication gastric cancer (GC) using VPZ regimen remain unclear. Methods This single-center cohort study included 934 consecutive patients who underwent H. pylori eradication using VPZ between February 2015 and June 2017 and were followed up for five years by the end of 2022. We examined several indicators of systemic immune, inflammatory, and nutritional status at the time of eradication to identify those indicators could predict eradication success, risk of post-eradication GC development, and long-term prognosis. Results The successful eradication rates were 92.6% (intention-to-treat) and 98.7% (per-protocol). Multivariate analysis showed that only a high peripheral blood neutrophil-to-lymphocyte ratio (NLR) was significantly associated with eradication failure. The 5-year GC incidence rate was 1.67%, and all GCs were stage IA. The mean (standard deviation [SD]) time from eradication to diagnosis was 40.5 (6.1) months. Multivariate analysis showed that high NLR and history of GC and hypertension were significantly associated with GC development. Patients with elevated NLR post-eradication had a higher risk of newly developed GC. Twelve patients died during the study period, and a high NLR was associated with a significantly higher mortality rate. Conclusions NLR has the potential to be a biomarker that predicts the failure of eradication and development of post-eradication GC. High NLR was also associated with poor long-term prognosis after H. pylori eradication.

The Prognostic Role of Pre-Treatment Neutrophil-to-Lymphocyte Ratio in an Asian Cohort of Patients with Oropharyngeal Squamous Cell Carcinoma

Purpose: The neutrophil-to-lymphocyte ratio is a simple biomarker that reflects the balance between the systemic inflammatory and immunity status. Here we investigate the prognostic role of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in an Asian cohort of oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: A retrospective review of OPSCC patients from a tertiary institution was conducted. The NLR was calculated from the haematological specimen taken within a month before treatment. Survival rates were estimated via the Kaplan–Meier method, and Cox proportional hazards regression was performed for univariable and multivariable analyses. The NLR cutpoint was determined using maximally selected log-rank statistics. Results: In a cohort of 148 OPSCC patients, 43% were p16-positive and 44% were p16-negative, with a median follow-up of 24 months. The p16-positive patients were younger (median age 62 vs. 67 years) and exhibited a lower prevalence of heavy smoking (47% vs. 69%). The p16-negative cases frequently presented at an advanced disease stage (74% vs. 41%), with a history of previous radiotherapy (26% vs. 3%). The p16-negative patients displayed a higher median NLR (2.91 vs. 2.49). The 3-year disease-specific survival (DSS) in p16-positive was higher compared to p16-negative patients (89.9% vs. 41.6%). The optimal NLR cutpoint was determined as 3.56 and predicted for decreased DSS (hazard ratio [HR] 2.59, p = 0.004). Multivariable analysis revealed smoking, high NLR ≥ 3.56, and p16-negativity as independent variables associated with poorer DSS and overall survival (OS) across the cohort. Conclusion: A high NLR is independently prognostic of poorer DSS in OPSCC, independent of p16 and smoking status. A NLR of more than 3.56 was highly prognostic for poorer survival and warrants further validation in larger cohorts of OPSCC.

Abstract 4132149: Elevated Levels of Plasma Mitochondrial DNA Damage-Associated Molecular Patterns (DAMPS) in Humans and Dogs with Heart Failure and Reduced Ejection Fraction

Background: Heart failure (HF) with reduced ejection fraction (HFrEF) is associated with increased inflammatory response that contributes to progressive worsening of the HF state. Potential endogenous triggers of this process include damage-associated molecular patterns (DAMPs). DAMPs originate from within cells following tissue stress or injury and activate pattern recognition receptors of the immune system, triggering an inflammatory response. Mitochondria are the major cell organelles that release DAMPs into the circulation. Chronic HF is associated with multi-organ mitochondrial dysfunction and cell injury and death. Purpose: The present study sought to quantify differences in mitochondrial DNA (mtDNA) DAMPs in the setting of HFrEF in humans and dogs compared to normal humans and dogs. Methods: Plasma samples were obtained from 9 HFrEF patients with left ventricular ejection fraction (LVEF) ≤35% and 9 age-matched healthy subjects, and from 6 dogs with coronary microembolization-induced HF (LVEF ≤35%) and 6 normal dogs. DNA fragments were isolated from 1 ml of plasma using a commercially available kit. Quantitative PCR and specifically designed primers were used to measure the amount of DNA in plasma from COX1 (cytochrome c oxidase subunit 1), ND1 (NADH dehydrogenase subunit 1) and ND6 (NADH dehydrogenase subunit 6) using an Applied Biosystems 7500 Fast-PCR unit. The relative abundances of plasma mtDNA DAMPs were expressed as threshold cycles (C T ). Results: Compared to normal human subjects, mtDNA DAMPs levels of COX1 , ND1 and ND6 in plasma of HFrEF patients was 4-fold, 9-fold and 8-fold greater, respectively. Similarly, compared to normal dogs, mtDNA DAMPs levels of COX1 , ND1 and ND6 in plasma of HFrEF dogs was increased 48-fold, 12-fold and 4-fold, respectively. Conclusions: These findings indicate a marked increase of mtDNA DAMPs in plasma of humans and dogs with HFrEF. The increase of mtDNA DAMPs is consistent with the elevated systemic inflammatory state of HFrEF. The results underscore mitochondrial abnormalities as integral players in the progressive worsening of HFrEF.

Dietary exposure to di (2-ethylhexyl) phthalate (DEHP) for 6months alters markers of female reproductive aging in mice.

The female reproductive system ages before any other physiological system, making it a sensitive indicator of aging. Early reproductive aging is associated with the early onset of infertility and an increased risk of several diseases. During aging, systemic and reproductive oxidative stress and inflammation levels increase through inflammasome activation, leading to ovarian follicle loss. Other markers of reproductive aging include increased fibrosis and shortening of telomeres in ovarian cells. The factors that accelerate reproductive aging are unclear, but likely involve exposure to endocrine-disrupting chemicals such as phthalates. Di(2-ethylhexyl) phthalate (DEHP) is a widely used phthalate and humans are exposed to it daily. Several studies show that DEHP induces reproductive toxicity by affecting estrous cyclicity, follicle numbers, and hormone levels. However, little is known about the mechanisms underlying DEHP-induced early onset of reproductive aging. Thus, this study tested the hypothesis that dietary exposure to DEHP induces early reproductive aging by affecting inflammation, fibrosis, and the expression of telomere regulators and antioxidant enzymes. Adult CD-1 female mice were exposed to vehicle (corn oil) or DEHP (0.5, 1.5, or 1500ppm) via the chow for six months. Exposure to DEHP increased the expression of antioxidant enzymes and Casp3, increased expression of telomere-associated genes, and increased fibrosis levels in the ovary. In addition, DEHP exposure for 6months altered ovarian and systemic inflammatory status. Collectively, our novel data suggest that 6-month dietary exposure to DEHP may accelerate reproductive aging by affecting several reproductive aging markers in female mice.

Contribution of gut microbiota to the development of Crohn's disease: Insights gained from fecal microbiota transplantation studies in mice.

We would like to present some new thoughts on the publication in the journal published in August 2024 in World Journal of Gastroenterology. We specifically focused on the alterations in the intestinal tract, mesenteric adipose tissue (MAT), and systemic inflammatory changes in mice following fecal flora transplantation into a mouse model of Crohn's disease (CD). Accumulating evidence suggests that the occurrence of CD is influenced by environmental factors, host immune status, genetic susceptibility, and flora imbalance. One microbiota-based intervention, fecal microbiota transplantation, has emerged as a potential treatment option for CD. The MAT is considered a "second barrier" around the inflamed intestine. The interaction between gut microbes and inflammatory changes in MAT has attracted considerable interest. In the study under discussion, the authors transplanted fetal fecal microorganisms from patients with CD and clinically healthy donors, respectively, into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice. The research explored the complex interplay between MAT, creeping fat, inflammation, and intestinal flora in CD by evaluating intestinal and mesenteric lesions, along with the systemic inflammatory state in the mice. This article provides several important insights. First, the transplantation of intestinal flora holds significant potential as a therapeutic strategy for CD, offering hope for patients with CD. Second, it presents a novel approach to the diagnosis and treatment of CD: The inflammatory response in CD could potentially be assessed through pathological or imaging changes in the MAT, and CD could be treated by targeting the inflammation of the MAT.

Electrochemical Profiling of vWFA2 for Systemic Inflammatory State Detection

Electrochemical Profiling of vWFA2 for Systemic Inflammatory State Detection

The prognostic value of advanced lung cancer inflammation index in cancer survivors complicated with cardiovascular disease

Abstract Background The advanced lung cancer inflammation index (ALI) reflects systemic inflammatory and nutritional status, both of which are related to the prognosis of the disease. However, the prognostic value of ALI in cancer survivors with cardiovascular disease (CVD) remains unclear. Purpose This study was conducted to investigate the association of ALI with mortality in cancer survivors with CVD. Methods This study enrolled 955 cancer survivors with CVD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018), and followed mortality status until December 31, 2019. Cox proportional hazards regression analysis and threshold effect analysis were applied to evaluate the relationship between ALI and all-cause, CVD-specific, and cancer-specific mortality. The prognostic value of ALI was further examined by time-dependent receiver operating characteristic (ROC) curve analysis. Results During a median follow-up period of 66.65 months, 490 all-cause deaths were observed, including 181 CVD-specific deaths and 121 cancer-specific deaths. After multivariate adjustment, ALI was inversely associated with all-cause, CVD-specific, and cancer-specific mortality in cancer survivors with CVD. Furthermore, L-shaped associations of ALI with mortality were discovered, with inflection points of 74.18 for all-cause and CVD-specific mortality and 55.50 for cancer-specific mortality. When the ALI was less than the inflection points, a 10-unit increase of ALI was associated with a 16%, 16%, and 25% decreased HR for all-cause, CVD-specific, and cancer-specific mortality, respectively. The time-dependent ROC curve analysis showed that the ALI had moderate predictive value for short- and long-term mortality. Conclusions The ALI is a significant prognostic indicator of mortality for cancer survivors with CVD. The findings allow for early prevention to improve the overall prognosis in such populations.

Evaluation of naples prognostic score to predict long-term mortality in patients with pulmonary embolism

Abstract Background/Introduction APE mortality rates are still not satisfactory despite new diagnosis and treatment methods (1). Thus, risk classification is crucial due to the wide range of clinical presentations. Several risk stratifications have been developed such as simplified Pulmonary Embolism Severity Index (sPESI) (2). Nonetheless, there remains a need for an optimal indicator that can be conveniently measured with a high degree of precision to predict clinical outcomes. Naples prognostic score (NPS) is a newly defined index that is developed to determine the prognosis of cancer patients and reflects the inflammatory and nutritional status of the patients (3). Purpose The aim of our study was to determine the long-term prognostic value of NPS in APE patients. Methods Two hundred ninety-three patients diagnosed with APE between November 2016 and February 2022 were included in the study. NPS consists of 4 parameters: serum albumin, total cholesterol (TC) concentration, neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Naples scores of all patients were calculated and the patients were divided into 2 groups according to their NPS and their long-term mortality was compared. The primary endpoint of the study was long-term mortality. Results The long-term mortality was observed in 38 patients out of 293 patients in the mean follow-up of 24 (16-42) months. In the low-Naples risk group (group 1), there were 215 patients, while the high-Naples risk group (group 2) had 78 patients. Multivariate analysis showed that NPS as a categorical parameter (HR: 3.458, 95%CI:1.734-6.896, p<0.001), NPS as a numerical parameter, (HR:1.651, 95%CI:1.217-2.241, p=0.001) and simplified pulmonary embolism severity index (sPESI) (HR:1.887, 95%CI:1.223-2.911), p=0.004) score were independent predictors of long-term mortality. The receiver operating characteristic curve analysis showed that the model 2 with NPS as continuous had higher discriminative ability than the baseline model for detecting patients with mortality (Area under curve (AUC) values = 0.791 vs. 0.723, respectively, p=0.04) (Figure 1A). The long-term predictive capability of NPS was non-inferior than the sPESI score (Figure 1B). Conclusions The current study highlights that NPS, which reflects systemic inflammation and nutritional status may have potential to predict long-term mortality in APE patients. To our knowledge, this is the first study to show the relationship between long-term mortality and NPS in APE patients.

Identification of the optimal method for measuring left atrium volume as a marker of undetected atrial fibrillation in patients with cryptogenic stroke and high prevalence of overweight

Abstract Introduction Paroxysmal atrial fibrillation (AF) is detected in approximately one-third of patients diagnosed with cryptogenic stroke undergoing prolonged ECG monitoring. Several risk factors for AF have been described, including left atrium (LA) enlargement, LA deformation, age, cardiovascular risk factors, and biomarkers as N-pro-BNP and troponin. Specifically, LA enlargement is a direct marker of atrial cardiopathy, which predisposes to AF. However, the methods to calculate LA enlargement vary. While LA biplane volume indexed to body surface area (BSA) remains the standardized method of choice according to current guidelines, it may underestimate the degree of enlargement in overweight patients. Additionally, overweight produces a systemic inflammatory state which is also associated with AF. Purpose The primary objective of the study was to define the best parameter among LA end systolic volume (LAESV), LAESV indexed to BSA (LAESV/BSA), and LAESV indexed to ideal BSA for identifying patients admitted for cryptogenic stroke with undetected paroxysmal AF. The secondary objective was to assess the accuracy of these parameters in both normal-weight and overweight patients. Methods Consecutive patients over 65 years-old diagnosed with cryptogenic stroke in our tertiary hospital were enrolled. All patients underwent 15-days ambulatory ECG monitoring to screen for undetected paroxysmal AF. Clinical, echocardiographic and laboratory data were prospectively collected. Ideal BSA was calculated using the Devine method. The accuracy of LA volume parameters in classifying patients with undetected paroxysmal AF was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The analysis was stratified for overweight status (BMI < 25 or BMI ≥ 25). Results A total of 66 patients (Mean age 78.4 ± 7.6 years; 48% male) were included. Of them, 39 (59%) had hypertension, 16 (24%) had diabetes and 39 (59%) were overweight. AF was present in 21 (32%) patients. The mean LAESV, LAESV/BSA, LAESV/ideal BSA were 56.2 ± 23.0 ml, 34.2 ± 12.6 ml/m2, and 34.7 ± 14.1 ml/m2, respectively. Figure 1 illustrates the ROC curves for LA volume parameters in the main cohort and stratified by overweight status. Overall, no relevant differences in AUC were observed among LAESV, LAESV/BSA, LAESV/ideal BSA in each scenario. However, BMI significantly altered the discrimination performance of LA volume measures, which resulted optimal in normal-weight patients (AUC from 0.838 to 0.886) and absent in overweight patients (AUC from 0.838 to 0.521 to 0.564). Conclusions LAESV, LAESV/BSA, LAESV/ideal BSA show similar discrimination performance in identifying undetected AF in patients with cryptogenic stroke. However, the presence of overweight considerably impacts on the predictive value of LA volume parameters in this clinical scenario.ROC curves

Metataxonomics and Metabolomics Profiles in Metabolic Dysfunction-Associated Fatty Liver Disease Patients on a “Navelina” Orange-Enriched Diet

Background/Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD) is currently the most common cause of chronic liver disease. Systemic inflammatory status and peripheral metabolic symptoms in the clinical picture have an impact on gut commensal bacteria. Methods: Our designed clinical trial was based on a cohort of patients with MAFLD whose diet included the daily consumption of 400 g of “Navelina” oranges for 28 days, compared with a control group of patients with the same pathologic conditions whose diet did not include the consumption of oranges and other foods containing similar nutrients/micronutrients. We used 16S metataxonomics and GC/MS analyses to identify taxa and urine/fecal VOCs, respectively. Results: A set of micronutrients from the diet were inspected, and some specific fatty acids were identified as the main contributors in terms of cluster sample separation. Metataxonomics and metabolomics profiles were obtained, and a stringent statistical approach allowed for the identification of significant taxa/VOCs, which emerged from pairwise group comparisons in both fecal and urine samples. Conclusions: In conclusion, a set of taxa/VOCs can be directly referred to as a marker of dysbiosis status and other comorbidities that, together, make up the pathologic burden associated with MAFLD. The investigated variables can be a target of therapeutic strategies.

Exploring the association between hemoglobin, albumin, lymphocyte, and platelet score and all-cause mortality among middle-aged and older patients with osteoarthritis.

Integrating hemoglobin, albumin, lymphocyte, and platelets (HALP) scores can simultaneously reflect systemic inflammation and nutritional status. Some evidence suggests its prognostic value in certain malignancies, however, the impact of HALP on individuals with osteoarthritis (OA) who are middle-aged and older remains unknown. This retrospective cohort study included 3566 individuals from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. The study endpoint was the all-cause mortality of OA patients. Weighted Cox models were used to assess the relationship between HALP score and all-cause mortality. Subgroup analyses stratified by age, gender, diabetes, dyslipidemia, and cardiovascular disease were conducted. After the follow-up was terminated, 920 participants experienced all-cause mortality, and 2646 participants survived. After adjusting for covariates, the continuous analysis revealed an inverse association between HALP score and all-cause mortality (hazard ratio (HR) = 0.89, 95% confidence interval (CI): 0.83-0.95). The categorical analysis indicated that the lowest quartile of HALP score was related to higher all-cause mortality by using the highest quartile of HALP score as a reference (HR = 1.46, 95% CI: 1.18-1.81). The association between HALP score with lowest quartile and all-cause mortality remained significant across different subgroups. This study suggested that HALP score was linked with all-cause mortality among middle-aged and older individuals diagnosed with OA, thereby indicating its potential as a reliable prognostic indicator for this patient population.

Thrombotic, Cardiovascular, and Microvascular Complications of Myeloproliferative Neoplasms and Clonal Hematopoiesis (CHIP): A Narrative Review.

The most common causes of morbidity and mortality in the myeloproliferative neoplasms (MPNs), with the exception of myelofibrosis, are venous and arterial thrombosis, as well as more recently discovered cardiovascular disease (CVD). Clonal hematopoiesis of indeterminate potential (CHIP) is the subclinical finding in an individual of somatic mutations that are also found in clinically overt MPNs and other myeloid malignancies. The prevalence of "silent" CHIP increases with age. CHIP can transform into a clinically overt MPN at an estimated rate of 0.5 to 1% per year. It is likely, therefore, but not proven, that many, if not all, MPN patients had antecedent CHIP, possibly for many years. Moreover, both individuals with asymptomatic CHIP, as well as clinically diagnosed patients with MPN, can develop thrombotic complications. An unexpected and remarkable discovery during the last few years is that even CHIP (as well as MPNs) are significant, independent risk factors for CVD. This review discusses up-to-date information on the types of thrombotic and cardiovascular complications that are found in CHIP and MPN patients. A systemic inflammatory state (that is often subclinical) is most likely to be a major mediator of adverse reciprocal bone marrow-cardiovascular interplay that may fuel the development of progression of MPNs, including its thrombotic and vascular complications, as well as the worsening of cardiovascular disease, possibly in a "vicious cycle". Translating this to clinical practice for hematologists and oncologists who treat MPN patients, attention should now be paid to ensuring that cardiovascular risk factors are controlled and minimized, either by the patient's cardiologist or primary care physician or by the hematologist/oncologist herself or himself. This review is intended to cover the clinical aspects of thrombosis and cardiovascular complications in the MPN, accompanied by pathobiological comments.

Is the hemoglobin, albumin, lymphocyte, and platelet (HALP) score a novel biomarker for predicting mortality in patients with middle cerebral artery infarctions undergoing mechanical thrombectomy?

BackgroundThe hemoglobin, albumin, lymphocyte, and platelet (HALP) score, easily calculated parameter, indicating systemic inflammation and nutritional status IntroductionIn this study, we used the HALP score in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT) to predict 90-day mortality. Method122 patients with AIS who underwent either MT or MT and tissue plasminogen activator (tPA) for middle cerebral artery (MCA) M1 occlusion. The HALP score was calculated, demographic data, modified Rankin Scale (mRS) score, and mortality status in retrospectively reviewed. The effectiveness of the HALP score in predicting mortality within 90 days was assessed using the receiver operating characteristic ( ROC) curves. The optimal cutoff value for HALP was 13.10. ResultsA HALP score <13.10 increased the risk of death within 90 days and was associated with a higher incidence of large artery thrombosis. Cardioembolism and hyperlipidemia were more common in patients with high (>13) HALP scores. In addition to the HALP score, the length of hospital stay, 24-h National Institutes of Health Stroke Scale score (NIHSS), number of days of intubation, acute physiologic assessment and chronic health evaluation (APACHE) II score, and symptom-to-groin time were statistically significant risk factors for mortality within 90 days. DiscussionThe HALP score is an easily calculated, inexpensive, and noninvasive parameter that can be used to predict mortality in patients with MCA M1 occlusion undergoing reperfusion therapy. Low HALP scores indicate a poor prognosis. Thus, there is a relationship between the HALP score and survival.

The prognostic role of pan-immune inflammation value in patients with metastatic castration resistance prostate cancer treated with Lutetium-177 (177Lu)-PSMA-617.

Pan-immune inflammation value (PIV) is a newly defined biomarker that includes whole cellular components that are indicators of systemic inflammation in complete blood count (CBC), easily accessible and has the potential to reflect both the body's immune response and systemic inflammation status. This study evaluated the pretreatment PIV for its prognostic impact on overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (177Lu)-PSMA-617. The PIV was based on the earliest CBC obtained within 1 month before treatment initiation. Patients were categorized into low and high PIV groups based on the median pretreatment PIV, and the relationship between OS and PIV groups was assessed by multivariable analysis. A total of 43 patients with mCRPC treated with (177Lu)-PSMA-617 were included. The median OS was longer in the low PIV group (15.1 months [95% confidence interval [CI] 10.6-19.5]) than in the high PIV group (4.2 months [95% CI 1.7-6.6]) (p < 0.001). In multivariable analysis, high PIV (hazard ratio [HR]: 4.3, 95% CI 1.194-15.93, p = 0.026) and high Eastern Cooperative Oncology Group performance score (HR: 7.05, 95% CI 1.48-33.46, p = 0.014) were associated with shorter OS. This study showed that pretreatment PIV might be a prognostic factor in patients with mCRPC treated with (177Lu)-PSMA-617.

Targeting leptin/CCL3-CCL4 axes in NAFLD/MAFLD: A novel role for BPF in counteracting thalamic inflammation and white matter degeneration

Non-alcoholic fatty liver disease (NAFLD), redefined as Metabolic Associated Fatty Liver Disease (MAFLD), is characterized by an extensive multi-organ involvement. MAFLD-induced systemic inflammatory status and peripheral metabolic alteration lead to an impairment of cerebral function. Herein, we investigated a panel of leptin-related inflammatory mediators as predictive biomarkers of neuroinflammation and evaluated the possible role of Bergamot Polyphenolic Fraction (BPF) in counteracting this MAFLD-induced inflammatory cascade. Male DIAMOND mice were randomly assigned to fed chow diet and tap water or high fat diet with sugar water. Starting from week 16, mice were further divided and treated with vehicle or BPF (50 mg/kg/day), via gavage, until week 30. Magnetic resonance imaging was performed at the baseline and at week 30. Correlation and regression analyses were performed to discriminate the altered lipid metabolism in the onset of cerebral alterations. Steatohepatitis led to an increase in leptin levels, resulting in a higher expression of proinflammatory mediators. The inflammatory biomarkers involved in leptin/CCL3-CCL4 axes were correlated with the altered thalamus energetic metabolism and the white matter degeneration. BPF administration restored leptin level, improved glucose and lipid metabolism, and reduced chronic low-grade inflammatory mediators, resulting in a prevention of white matter degeneration, alterations of thalamus metabolism and brain atrophy. The highlighted positive effect of BPF, mediated by the downregulation of the inflammatory biomarkers involved in leptin/CCL3-CCL4 axes, affording novel elements to candidate BPF for the development of a therapeutic strategy aimed at counteracting MAFLD-related brain inflammation.

Autonomic neuromodulation for cardiomyopathy associated with metabolic syndrome - Prevention of precursors for heart failure with preserved ejection fraction.

Metabolic syndrome (MetS) induces a systemic inflammatory state which can lead to cardiomyopathy, manifesting clinically as heart failure (HF) with preserved ejection fraction (HFpEF). MetS components are intricately linked to the pathophysiologic processes of myocardial remodeling. Increased sympathetic nervous system activity, which is noted as an upstream factor of MetS, has been linked to adverse myocardial structural changes. Since renal denervation and vagus nerve stimulation have a sympathoinhibitory effect, attention has been paid to the cardioprotective effects of autonomic neuromodulation. In this review, the pathophysiology underlying the relationship between MetS and HF is elucidated, and the evidence regarding autonomic neuromodulation in HFpEF is summarized.

Association of the systemic inflammation and anthropometric measurements with cancer risk: a prospective study in MJ cohort.

To investigate the specific role of inflammation in the connection between obesity and the overall incidence of cancer. A total of 356,554 participants in MJ cohort study were included. Systemic inflammation markers from blood samples and anthropometric measurements were determined using professional instruments. The Cox model was adopted to evaluate the association. Over a median follow-up of 8.2 years, 9,048 cancer cases were identified. For individual systemic inflammation biomarkers, the overall cancer risk significantly escalated as blood C-reactive protein (CRP) (hazard ratio (HR)=1.036 (1.017-1.054)) and globulin (GLO) (HR=1.128 (1.105-1.152)) levels increased, and as hemoglobin (HEMO) (HR=0.863 (0.842-0.884)), albumin (ALB) (HR=0.846 (0.829-0.863)) and platelets (PLA) (HR=0.842 (0.827-0.858)) levels decreased. For composite indicators, most of them existed a significant relationship to the overall cancer risk. Most indicators were correlated with the overall cancer and obesity-related cancer risk, but there was a reduction of association with non-obesity related cancer risk. Most of indicators mediated the association between anthropometric measurements and overall cancer risk. Systemic inflammatory state was significantly associated with increased risks of cancer risk. Inflammation biomarkers were found to partly mediate the association between obesity and cancer risk.

Association of Biomarkers with the Severity of Depression

Background: The pathogenesis of depression remains elusive and uncertain. The literature suggests that low-grade systemic inflammation might contribute to the etiology of depression. Other markers that are studied are serum magnesium and serum cortisol. The association between these factors might help understand the etiology. Methods: This was a cross-sectional study conducted on a sample of 40 participants. Socio-demographic data was noted, and the Hamilton depression rating scale was applied to rate the severity of depression. Blood samples were drawn at 8 a.m. to record a complete blood picture (to derive the neutrophil–lymphocyte ratio (NLR)), C-reactive protein, serum magnesium, and serum cortisol. Results: In this study, conducted on a sample size of 40, inflammatory markers such as C-reactive protein (CRP: mg/dl) and NLR were significantly increased to 15.52 ± 13.10 and 6.46 ± 2.92, respectively, showing an underlying inflammatory pathology. Serum cortisol (µg/dl) was also raised to 22.30 ± 5.46, and there was a fall in serum magnesium. Also, it is noteworthy that all these markers were significantly associated with the severity of depression, as the Pearson correlation between the Hamilton depression rating scale-21 item (HAM-D-21) score and CRP, NLR, and serum cortisol was positive and statistically significant ( r = 0.55, p &lt; .01; r = 0.51, p = .01; r = 0.46, p = .002). The Pearson correlation between the HAM-D score and serum magnesium was negative and statistically significant ( r = -0.82, p &lt; .01) Conclusion: There is a state of systemic inflammation, hypercortisolemia, and hypomagnesemia in depressive disorders.

Systemic Immune-inflammation Index in Evaluation of Inflammation in Rheumatoid Arthritis Patients.

To evaluate the systemic immune-inflammation (SII) index in patients with rheumatoid arthritis (RA) stratified by systemic inflammatory status. Seropositive patients with RA (n=58) were divided into two groups based on serum hs-C-reactive protein (hs-CRP) levels: RA patients with hs-CRP levels of at or 3 mg/L or above (high systemic inflammatory status; n=38) and RA patients with hs-CRP levels of less than 3 mg/L (low systemic inflammatory status; n=20). The control group comprised 31 healthy individuals. Blood samples were tested for the next parameters: leukocytes, neutrophilic granulocytes, lymphocytes, thrombocytes [platelet (PLT)], high-sensitivity hs-CRP, sed rate [erythrocyte sedimentation rate (ESR)], neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). The SII index was derived as Neu x PLT/Lym. In patients with RA, the SII index was elevated compared with that of healthy individuals and positively correlated with hs-CRP, erythrocyte sedimentation rate, NLR, MLR, PLR, tender joint count, and swollen-to-tender joint count ratio. Patients with RA who had hs-CRP levels of 3 mg/L above exhibited a statistically significant increase in the SII compared with those with hs-CRP levels below 3 mg/L. Additionally, within the cohort of RA patients with hs-CRP levels at or above 3 mg/L, a positive correlation was found between the SII index and both NLR and PLR. The SII index was positively correlated with NLR, MLR, and PLR in RA patients with hs-CRP levels below 3 mg/L. The cut-off point of the SII index for distinguishing between RA cases with hs-CRP levels 3 mg/L and those with hs-CRP levels 3 mg/L or higher was ≥323.4, with a sensitivity of 77.6% and a specificity of 54.8%. The serum SII index can be a potentially useful marker for evaluating the inflammatory process and clinical progression of RA.