Xinmailong injection on left ventricular remodeling and inflammatory mediators in patients with CHF: a systematic review and meta-analysis.

Background: Chronic heart failure (CHF) is a prevalent and highly challenging cardiovascular disease associated with high mortality rates. The occurrence and progression of CHF are closely linked to left ventricular remodeling (LVR) and inflammation. Addressing LVR and reducing inflammation can significantly slow down the progression of CHF and improve patient prognosis. Objective: To evaluate the effects of Xinmailong injection (XMLI) on LVR and inflammatory mediators in CHF patients. Method: The randomized controlled trials investigating the effectiveness of XMLI treatment for CHF were retrieved from eight databases up until 31 December 2023. To evaluate the methodological quality of included studies, the Cochrane bias risk tool was employed. Furthermore, statistical analysis, sensitivity analysis, and publication bias assessment were conducted using Stata 17.0 software. Result: Compared with conventional treatment (CT), the combination therapy of XMLI and CT significantly improved LVR and reduced inflammatory mediators, mainly manifested by an increase in LVEF (MD = 6.40, 95% CI: 5.25 to 7.55, p = 0.000), a decrease in LVEDD (MD = -4.63, 95% CI: -5.69 to -3.57, p = 0.000) and LVESD (MD = -4.00, 95% CI: -5.50 to -2.50, p = 0.000), as well as a decrease in TNF-α (MD = -7.93, 95% CI: -9.86 to -6.00, p = 0.000), IL-6 (MD = -5.25, 95% CI: -6.59 to -3.92, p = 0.000), IL-18 (MD = -36.07, 95% CI: -46.76 to -25.38, p = 0.000), CRP (MD = -4.41, 95% CI: -6.40 to -2.42, p = 0.000), hs-CRP (MD = -4.90, 95% CI: -5.71 to -4.08, p = 0.000), and an increase in IL-10 (MD = 20.19, 95% CI: 10.42 to 29.97, p = 0.000). In addition, the combination therapy showed enhanced clinical efficacy (OR = 4.08, 95% CI: 3.10 to 5.37, p = 0.000), decreased expression levels of BNP (MD = -138.48, 95% CI: -155.48 to -121.48, p = 0.000), and NT-pro BNP (MD = -315.63, 95% CI: -359.25 to -272.00, p = 0.000), and increased the 6-MWD (MD = 71.02, 95% CI: 57.23 to 84.81, p = 0.000). It is noteworthy that the combination therapy did not lead to an increase in the incidence of adverse reactions (OR = 1.01, 95% CI: 0.68 to 1.50, p = 0.97). Conclusion: This systematic review and meta-analysis demonstrated the superiority of combining XMLI and CT therapies over CT alone in improving LVR and reducing inflammatory mediators in patients with CHF. Importantly, this combination therapy does not increase adverse reactions. However, it is crucial to exercise caution while interpreting the survey results due to the limited quality of the included studies.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=492715, Identifier CRD42023492715.

Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties.

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial-mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient's age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences.

Mediators of Periodontitis complementing the development of Neural Disorders.

As a common oral health concern, periodontitis has been a source of attention for the global health community because of its linkage with systemic and neurological diseases. The purpose of the present study is to reveal the mediating role of specific cytokines, neuropeptides, and pathogens in the association of chronic periodontitis and neural disorders. To find the related literature different search engines namely PMC, Science Direct, PubMed, Research Gate, and Google Scholar were explored for a study period of five months from October 2022 to February 2023. This review offers a summary of those neuronal diseases that were more related to human behaviors in association with chronic periodontitis. Those neuronal pathologies mainly included Alzheimer's disease, psychosis, stress, anxiety, dementia, Alzheimer's, major depressive disorder, and diabetic peripheral neuropathy, which may otherwise remain subside or even control in the absence of chronic periodontitis and its mediators. Specifically, periodontitis related specific cytokines i.e. IL-6, IL-1, Tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and alpha1-antichymotrypsin, neuropeptides such as insulin-like growth factor-2 (IGF-2), neuropeptide Y, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP), and a polybacterial pathogenic consortium of porphyromonas gingivalis, tannerella forsythia, and treponema denticola, were involved in the mediation and exacerbation of the associated neuronal cognitive pathologies.

Interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein for optimal immunometabolic profiling of the lifestyle-related cardiorenal risk.

OBJECTIVES: The present study aimed to identify optimal inflammatory biomarkers involved in cardiorenal risk in response to major lifestyle factors. METHODS: One hundred and twenty-nine adults aged 35-77 years participated voluntarily from 2017 to 2019 (Córdoba, Argentina) in a cross-sectional study to collect sociodemographic, clinical, and lifestyle data. Blood biomarkers (different cytokines, monocyte chemoattractant protein-1 [MCP-1], and high-sensitivity C-reactive protein [hs-CRP]) were measured using standard methods and then evaluated by principal component analysis and structural equation modeling (SEM) according to Mediterranean diet adherence, physical activity level, and waist circumference, while cardiorenal risk involved blood diastolic pressure, HDL-cholesterol, triacylglycerols, creatinine, and glycosylated hemoglobin. RESULTS: A principal component included TNF-α (tumor necrosis factor-alpha), IL-8 (interleukin-8), IL-6 (interleukin-6), hs-CRP, and MCP-1, with absolute rotated factor loadings >0.10. SEM showed that IL-6 (ß=0.38, 95 % IC=0.08-0.68), hs-CRP (ß=0.33, 95 % IC=0.17-0.48), and TNF-α (ß=0.22, 95 % IC=0.11-0.32) were the mediators that better explained an inflammatory profile positively related to waist circumference (ß=0.77, 95 % IC=0.61-0.94). Moreover, this profile was associated with an increased cardiorenal risk (ß=0.78, 95 % IC=0.61-0.94), which was well-defined by the variable used. CONCLUSIONS: Immune mediators are key elements in profiling the cardiorenal risk associated with lifestyle factors, for which the combination of hs-CRP, IL-6, and TNF-α has emerged as a robust indicator. This work reaffirms the need for biomarker optimization for early diagnosis and risk assessment.

Inhibition of sepsis-induced pancreatic injury by leukotriene receptor antagonism via modulation of oxidative injury, and downregulation of inflammatory markers in experimental rats.

The purpose of this study is to investigate the effect of montelukast on lipopolysaccharide (LPS)-induced pancreatitis. Adult male Wistar rats were divided into 5 groups: normal control, control montelukast, LPS group, and two LPS + montelukast-treated groups. Acute pancreatitis (AP) was induced by a single dose of LPS (6 mg/kg, i.p.), while montelukast was given in two different doses (10 and 20 mg/kg/day) for 3 consecutive days prior to the injection of LPS. AP was demonstrated by significant increases in serum levels of lactate dehydrogenase (LDH) and pancreatic enzymes lipase and amylase. Proinflammatory response activation was evident by elevated serum levels of nitric oxide (NO) and increased pancreatic concentrations of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1ß), and intercellular adhesion molecule-1 (ICAM-1). The activity of myeloperoxidase (MPO), a neutrophil infiltration marker, has also been increased. Oxidative stress was confirmed by significant increases in the concentrations of lipid peroxides measured as thiobarbituric acid reactive substances (TBARS) and decreases in the concentrations of reduced glutathione (GSH) in the pancreatic tissues of animals treated with LPS. Histological examination confirmed the biochemical alterations. Montelukast treatment reversed all these biochemical indices and histopathological changes that LPS induced. Montelukast reduced the increase in serum levels of lipase, amylase, LDH, total nitrite/nitrate, TNF-α, IL-1ß, and ICAM-1. MPO activities and TBARS concentrations were also suppressed while GSH content was increased in pancreatic tissues. These results show that montelukast may be a beneficial pharmacological agent in protection against LPS-induced oxidative pancreatic injury by inhibiting neutrophil infiltration, counteracting oxidative stress, and suppressing inflammatory mediators.

New perspectives in cancer immunotherapy: targeting IL-6 cytokine family.

Chronic inflammation has been recognized as a canonical cancer hallmark. It is orchestrated by cytokines, which are master regulators of the tumor microenvironment (TME) as they represent the main communication bridge between cancer cells, the tumor stroma, and the immune system. Interleukin (IL)-6 represents a keystone cytokine in the link between inflammation and cancer. Many cytokines from the IL-6 family, which includes IL-6, oncostatin M, leukemia inhibitory factor, IL-11, IL-27, IL-31, ciliary neurotrophic factor, cardiotrophin 1, and cardiotrophin-like cytokine factor 1, have been shown to elicit tumor-promoting roles by modulating the TME, making them attractive therapeutic targets for cancer treatment.The development of immune checkpoint blockade (ICB) immunotherapies has radically changed the outcome of some cancers including melanoma, lung, and renal, although not without hurdles. However, ICB shows limited efficacy in other solid tumors. Recent reports support that chronic inflammation and IL-6 cytokine signaling are involved in resistance to immunotherapy. This review summarizes the available preclinical and clinical data regarding the implication of IL-6-related cytokines in regulating the immune TME and the response to ICB. Moreover, the potential clinical benefit of combining ICB with therapies targeting IL-6 cytokine members for cancer treatment is discussed.

Periodontal Effects of the Reversible Dipeptidyl Peptidase 1 Inhibitor Brensocatib in Bronchiectasis.

AIMS: Brensocatib is a reversible inhibitor of dipeptidyl peptidase 1 (cathepsin C), in development to treat chronic non-cystic fibrosis bronchiectasis. The phase 2, randomized, placebo-controlled WILLOW trial (NCT03218917) was conducted to examine whether brensocatib reduced the incidence of pulmonary exacerbations. Brensocatib prolonged the time to the first exacerbation and led to fewer exacerbations than placebo. Because brensocatib potentially affects oral tissues due to its action on neutrophil-mediated inflammation, we analyzed periodontal outcomes in the trial participants. MATERIALS AND METHODS: Patients with bronchiectasis were randomized 1:1:1 to receive once-daily oral brensocatib 10 or 25 mg or placebo. Periodontal status was monitored throughout the 24-week trial in a prespecified safety analysis. Periodontal pocket depth (PPD) at screening, week 8, and week 24 was evaluated. Gingival inflammation was evaluated by a combination of assessing bleeding upon probing and monitoring the Löe-Silness Gingival Index on 3 facial surfaces and the mid-lingual surface. RESULTS: At week 24, mean ± SE PPD reductions were similar across treatment groups: -0.07 ± 0.007, -0.06 ± 0.007, and -0.15 ± 0.007 mm with brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively. The distribution of changes in PPD and the number of patients with multiple increased PPD sites were similar across treatment groups at weeks 8 and 24. The frequencies of gingival index values were generally similar across treatment groups at each assessment. An increase in index values 0-1 and a decrease in index values 2-3 over time and at the end of the study were observed in all groups, indicating improved oral health. CONCLUSIONS: In patients with non-cystic fibrosis bronchiectasis, brensocatib 10 or 25 mg had an acceptable safety profile after 6 months' treatment, with no changes in periodontal status noted. Improvement in oral health at end of the study may be due to regular dental care during the trial and independent of brensocatib treatment. KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that 24 weeks of treatment with brensocatib does not affect periodontal disease progression. This information can be used by clinicians when considering treatment approaches for bronchiectasis and suggests that the use of brensocatib will not be limited by periodontal disease risks. Nevertheless, routine dental/periodontal care should be provided to patients irrespective of brensocatib treatment.

Association of dietary and blood inflammatory indicators with depression, anxiety, and stress in adults with vitamin D deficiency.

BACKGROUND: There is growing evidence that vitamin D may be related to mental health. The aim of the current study was to investigate the association of dietary and blood inflammatory factors with mental health disorders in subjects with vitamin D deficiency, shedding further light on the complex interplay of these conditions. METHOD: In this cross-sectional study, 306 subjects completed the validated Depression, Anxiety, and Stress Scale questionnaire to evaluate their depression, anxiety, and stress scores. Dietary inflammatory index (DII) and healthy eating index (HEI) were calculated using a validated 65-item food frequency questionnaire. Blood samples were taken and vitamin D, cytokine, and hs-CRP levels were measured using enzyme-linked immunosorbent assay kits. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) were calculated using standard laboratory methods. RESULTS: The subjects were divided into two groups based on their vitamin D levels: a vitamin D < 20 µg/dl group (N = 257) and a vitamin D ≥ 20  µg/dl group (N = 49). Between group analysis revealed that only DII (p = 0.015), platelet (p = 0.04), and hs-CRP (p = 0.015) were significantly different. In adults with vitamin D levels below 20 µg/dl, NLR and DII were significantly higher in subjects with anxiety (p < 0.05), and this relationship remained significant only for NLR after adjusting for age and sex. Additionally, PLR and HEI were significantly different in depressed compared to non-depressed subjects, and this association remained significant only for HEI after adjusting for age and sex. CONCLUSION: In subjects with vitamin D deficiency, increased levels of PLR, NLR, and DII were associated with depression and anxiety, while HEI was negatively associated with depression. These associations were not found in subjects with vitamin D levels ≥20 µg/dl.

Toxic retrobulbar neuritis due to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-based chronic sinusitis in the left sphenoid sinus: a case report.

BACKGROUND: Abrupt visual impairment constitutes a medical urgency, necessitating an interdisciplinary diagnostic and therapeutic approach owing to the broad spectrum of potential etiologies, thereby engaging numerous medical specialties. CASE PRESENTATION: A 21-year-old Mixed White and Asian female patient, with medical history of nonsteroidal antiinflammatory drug-exacerbated respiratory disease necessitating previous sinus surgery, reported sudden monocular vision loss. Unremarkable ophthalmological examination of the fellow eye and hematological parameters, save for a slight elevation in lymphocytes and eosinophils, were observed. Imaging studies indicated recurrence of bilateral chronic rhinosinusitis with nasal polyps and a mucocele in the left sphenoid sinus, accompanied by bony structural deficits. Emergency revision sinus surgery, guided by navigation, was promptly performed. The patient received treatment with methylprednisolone, ceftriaxone, cyanocobalamin, pyridoxine, thiamine, and acetylsalicylic acid. During the hospital stay, she developed steroid-induced glaucoma, which was subsequently managed successfully. Negative microbiological swabs, along with pathohistological evidence of increased tissue eosinophilia and the patient's clinical history, led to the diagnosis of toxic retrobulbar neuritis secondary to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-associated chronic rhinosinusitis of the left sphenoid sinus. CONCLUSIONS: In cases of acute unilateral vision loss, optic neuritis is a highly probable differential diagnosis and may be induced by pathologies of the paranasal sinuses. Nonsteroidal antiinflammatory drug-exacerbated respiratory disease, a subtype of chronic rhinosinusitis, is associated with type 2 inflammation, which is increasingly recognized for its role in the pathogenesis of bronchial asthma, eosinophilic esophagitis, and atopic eczema. Clinicians should consider chronic rhinosinusitis as a potential differential diagnosis in unilateral visual loss and be cognizant of the rising significance of type 2 inflammations, which are relevant to a variety of diseases.

Elevated Serum Galectin-1 and Galectin-3 Levels in Children With Specific Learning Disorder: A Case Control Study.

OBJECTIVE: Specific learning disorder (SLD) is a neurodevelopmental disorder in which underlying pathogenesis and etiological factors are not fully understood. Neuroinflammatory response (measured with serum levels of galectin-1 and galectin-3), which is associated with learning and memory, may play an important role in the etiopathogenesis of SLD. Aim of the present study is to examine whether serum galectin-1 and galectin-3 levels are related to SLD. METHODS: The current study consisted of 42 treatment-naive children with SLD and 42 control subjects. All of the subjects were assessed using semi-structured psychiatric examination to diagnose SLD and exclude attention-deficit hyperactivity disorder. Serum galectin-1 and galectin-3 levels were measured via venous blood samples. RESULTS: The SLD and control group did not differ significantly in terms of age, sex, and body mass index (BMI). The SLD group had significantly higher serum levels of galectin-1 (8.78±2.97 vs. 7.40±2.03, p=0.019) and galectin-3 (1.86±0.93 vs. 1.32±0.69, p=0.003) than the control group when controlled for age, sex, and BMI. CONCLUSION: Higher serum levels of galectin-1 and galectin-3 in children with SLD may indicate the role of neuroinflammatory response in the pathogenesis of SLD. Other mechanisms involving galectin-1 and galectin-3 related to learning may play a part in the etiology of SLD.

Kangfuxin alleviates ulcerative colitis in rats by inhibiting NF-κB p65 activation and regulating T lymphocyte subsets.

Objectives: Ulcerative colitis (UC) remains an enduring, idiopathic inflammatory bowel disease marked by persistent mucosal inflammation initiating from the rectum and extending in a proximal direction. An ethanol extract of Periplaneta americana L., namely Kangfuxin (KFX), has a significant historical presence in Traditional Chinese Medicine and has been broadly utilized in clinical practice for the treatment of injury. Here, we aimed to determine the effect of KFX on 2,4,6-trinitro'benzene sulfonic acid (TNBS)-induced UC in Sprague-Dawley rats. Materials and Methods: We established the UC model by TNBS/ethanol method. Then, the rats were subject to KFX (50, 100, 200 mg/kg/day) for 2 weeks by intragastric gavage. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), and histopathological score were evaluated. The colonic tissue interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), IL-10, transforming growth factor-1 (TGF-ß1), and epidermal growth factor (EGF) were determined by Elisa. To study T-lymphocyte subsets, flow cytometry was performed. In addition, the expression level of NF-κB p65 was evaluated by immunohistochemistry and western blot analysis. Results: Compared with the TNBS-triggered colitis rats, the treatment of rats with KFX significantly increased the body weight, and decreased DAI, CMDI, and histopathological score. Also, KFX elicited a reduction in the secretion of colonic pro-inflammatory cytokines, namely IL-1ß, IL-6, and TNF-α, concomitant with up-regulation of IL-10, TGF-ß1, and EGF levels. Upon KFX treatment, the CD3+CD4+/CD3+CD8+ ratio in the spleen decreased, while the CD3+CD8+ subset and the CD3+CD4+CD25+/CD3+CD4+ ratio demonstrated an increase. In addition, the expression of NF-κB p65 in the colon was decreased. Conclusion: KFX effectively suppresses TNBS-induced colitis by inhibiting the activation of NF-κB p65 and regulating the ratio of CD4+/CD8+.

Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies.

Cytokine storm induced by anti-human epidermal growth factor receptor-2 (HER2) therapies has not been reported. We report a patient with breast cancer treated with trastuzumab/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1ß, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this FcγR-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2 months of initial presentation, together with a resolution of the myocardial inflammation on MRI.

2,5-dimethylcelecoxib alleviated NK and T-cell exhaustion in hepatocellular carcinoma via the gastrointestinal microbiota-AMPK-mTOR axis.

BACKGROUND: 2,5-dimethylcelecoxib (DMC), a derivative of celecoxib, is an inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1). Our previous studies have demonstrated that DMC inhibits the expression of programmed death-ligand 1 on hepatocellular carcinoma (HCC) cells to prevent tumor progression. However, the effect and mechanism of DMC on HCC infiltrating immune cells remain unclear. METHODS: In this study, single-cell-based high-dimensional mass cytometry was performed on the tumor microenvironment of HCC mice treated with DMC, celecoxib and MK-886 (a known mPGES-1 inhibitor). Moreover, 16S ribosomal RNA sequencing was employed to analyze how DMC improved the tumor microenvironment of HCC by remodeling the gastrointestinal microflora. RESULTS: We found that (1) DMC significantly inhibited the growth of HCC and improved the prognosis of the mice, and this depended on the stronger antitumor activity of natural killer (NK) and T cells; (2) compared with celecoxib and MK-886, DMC significantly enhanced the cytotoxic and stem-like potential, and inhibited exhaustion of NK and T cells; (3) mechanistically, DMC inhibited the expression of programmed cell death protein-1 and upregulated interferon-γ expression of NK and T cells via the gastrointestinal microbiota (Bacteroides acidifaciens, Odoribacter laneus, and Odoribacter splanchnicus)-AMPK-mTOR axis. CONCLUSIONS: Our study uncovers the role of DMC in improving the tumor microenvironment of HCC, which not only enriches the relationship between the mPGES-1/prostaglandin E2 pathway and the antitumor function of NK and T cells, but also provide an important strategic reference for multitarget or combined immunotherapy of HCC.Cite Now.

Pathogenesis of Extraarticular Manifestations in Rheumatoid Arthritis-A Comprehensive Review.

Rheumatoid arthritis (RA) is among the most prevalent and debilitating autoimmune inflammatory chronic diseases. Although it is primarily characterized by destructive peripheral arthritis, it is a systemic disease, and RA-related extraarticular manifestations (EAMs) can affect almost every organ, exhibit a multitude of clinical presentations, and can even be asymptomatic. Importantly, EAMs largely contribute to the quality of life and mortality of RA patients, particularly substantially increased risk of cardiovascular disease (CVD) which is the leading cause of death in RA patients. In spite of known risk factors related to EAM development, a more in-depth understanding of its pathophysiology is lacking. Improved knowledge of EAMs and their comparison to the pathogenesis of arthritis in RA could lead to a better understanding of RA inflammation overall and its initial phases. Taking into account that RA is a disorder that has many faces and that each person experiences it and responds to treatments differently, gaining a better understanding of the connections between the joint and extra-joint manifestations could help to create new treatments and improve the overall approach to the patient.

The Influence of Fixed Dental Prostheses on the Expression of Inflammatory Markers and Periodontal Status-Narrative Review.

A dental prosthesis will only be successful if the restoration lasts for a long period and does not cause any illness. The presence of permanent prosthetic restorations has been linked to an increased risk of periodontal infections, according to a large body of research that has been gathered. When chronic inflammation is brought on by fixed prosthetic constructions, both cellular and noncellular immunity are activated as adaptive immune mechanisms. It has previously been stated that both clinically adequate and inadequate restorations might cause gingival inflammation. Areas surrounding the abutment teeth presented periodontal pockets, attachment loss, congestion, bleeding on probing, and gingival hyperplasia after fixed restorations were removed. The depth of pockets, bleeding on probing, and bone loss are all closely correlated with disease's severity and IL-1ß concentration in gingival crevicular fluid; IL-1ß shows higher values in disease sites than in healthy ones. hs-CRP and TNF-α blood levels showed a considerable reduction one day after fixed restorations were applied, in comparison with the pre-treatment values. Collaboration between prosthodontists and periodontists is essential for a good treatment outcome since it will increase the restoration's lifespan, enhance periodontal health, and improve the quality of life for dental patients.

The effects of Chlorella vulgaris on cardiovascular risk factors: A comprehensive review on putative molecular mechanisms.

High incidence rate of cardiovascular disease (CVD) make this condition as an important public health concern. The use of natural products in treating this chronic condition has increased in recent years one of which is the single-celled green alga Chlorella. Chlorella vulgaris (CV) has been studied for its potential benefits to human health due to its biological and pharmacological features. CV contains a variety of macro and micronutrients, including proteins, omega-3, polysaccharides, vitamins, and minerals. Some studies have indicated that taking CV as a dietary supplement can help reduce inflammation and oxidative stress. In some studies, cardiovascular risk factors that are based on hematological indices did not show these benefits, and no molecular mechanisms have been identified. This comprehensive review summarized the research on the cardio-protective benefits of chlorella supplementation and the underlying molecular processes.

Updated Trans-Ethnic Meta-Analysis of Associations between Inflammation-Related Genes and Intracranial Aneurysm.

OBJECTIVE: We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. METHODS: We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. RESULTS: Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56-0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80-1.47; p=0.5929). Three other variants, rs16944 (IL-1ß), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01

Development of Acute Transverse Myelitis following COVID-19 Infection: A Review on the Potential Pathways.

BACKGROUND: Acute transverse myelitis (ATM) is a rare neurological disorder in adults characterized by localized inflammation of gray and white matter in one or more contiguous spinal cord segments in the absence of a compressive injury. Several reports have connected the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the pathophysiology of ATM. SUMMARY: Direct invasion of the spinal cord, cytokine storm, or an autoimmune response are the possible pathways by which the SARS-CoV-2 virus can affect the spinal cord and lead to ATM. Direct invasion is facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) receptors on the membranes of the spinal cord neurons. Cytokine storm syndrome could be derived from elevated levels of several immunological factors following severe involvement with coronavirus disease 2019 (COVID-19). Finally, autoimmune responses can cause post-infectious ATM through several hypothesized processes, including molecular mimicry, epitope spreading, bystander activation, and polyclonal B-cell activation. KEY MESSAGES: COVID-19-induced ATM is mostly a longitudinally-extensive ATM (LEATM), in which more spinal cord segments are damaged, which results in a worse sequel compared to short-segment ATM. Therefore, it is suggested that COVID-19 patients, particularly severe cases, be followed up for a probable incidence of ATM, even long after recovery from the disease and elimination of the virus from the host, because an early diagnosis and effective therapy may stop the spread of inflammation to adjacent segments.

Systemic inflammatory syndromes as life-threatening side effects of immune checkpoint inhibitors: case report and systematic review of the literature.

Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events. As oncological indications for ICIs widen, their rare side effects become increasingly visible in clinical practice and impact therapy decisions.Here, we report a rare case of early-onset, mild cytokine release syndrome (CRS) in a patient who received ICIs for a metastasized renal cell carcinoma, which led to treatment discontinuation.We further provide a systematic review of the literature of CRS and related life-threatening side effects of ICI treatment, such as hemophagocytic lymphohistiocytosis (HLH). We searched Medline, Embase and the Web of Science Core Collection from inception to October 2021 for reports on CRS, cytokine storm, macrophage activation syndrome, HLH, and related hyperinflammatory disorders in patients with solid cancers receiving ICIs. We found n=1866 articles, which were assessed for eligibility independently by two examiners. Of those, n=49 articles reporting on n=189 individuals were eligible for review. We found that the median time from last infusion to the occurrence of CRS/HLH was approximately nine days, while the onset of symptoms varied from immediately after infusion to one month after treatment. Most patients were treated with either corticosteroids or the anti-interleukin 6 (IL-6) antibody tocilizumab, and although the majority of patients recovered, a few cases were fatal. Concomitant IL-6 and ICI treatment were reported as beneficial for both the antitumoral effect and for limiting side effects. Data from international pharmacovigilance databases underscored that ICI-related CRS and HLH are rare events, but we identified significant differences in reported frequencies, which might suggest substantial under-reporting.The results from this first systematic review of CRS/HLH due to ICI therapy highlight that life-threatening systemic inflammatory complications of ICIs are rare and might be associated with fatal outcome in approximately 10% of patients. Limited data support the use of IL-6 inhibitors in combination with ICIs to augment the antitumoral effect and reduce hyperinflammation.

Association of Interleukin-6 and Interleukin-8 with Cognitive Decline in an Asian Memory Clinic Population.

BACKGROUND: Neuroinflammation has been postulated to play an important role in cognitive impairment, cognitive decline, and dementia. Inflammatory biomarkers such as interleukin-6 (IL-6) and IL-8 are found to be associated with the neuro-inflammatory process and worse cognitive function. However, it is unknown whether these interleukins are associated with long-term cognitive function. OBJECTIVE: To investigate the association of baseline IL-6 and IL-8 with cognitive function at baseline as well as its association with cognitive decline over five-year follow-up. METHODS: 387 patients were recruited from an ongoing memory clinic-based study who underwent comprehensive physical, medical, neuropsychological and blood assessments together with brain MRI. IL-6 and IL-8 were measured using LUMINEX assays. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network neuropsychological battery was used to assess cognitive decline across multiple domains. RESULTS: Among the 387 (mean age = 72.9 years and 53.7% males) participants, 322 had at least two follow-up assessments and were included in the longitudinal analysis. Negative linear trend associations were found between tertiles of IL-8 with baseline global cognition (p-trend< 0.001), attention (p-trend = 0.005), executive function (p-trend< 0.001), and visuospatial function (p-trend = 0.002) domains. No association was found between baseline IL-8 and cognitive decline. IL-6 was not associated with both baseline and follow-up cognition. CONCLUSION: IL-8 was associated with worse cognition especially in attention, executive function, and visuospatial function, suggesting the role of neuroinflammation in cognitive impairment. Hence, blood inflammatory biomarkers may be useful indicators in identifying patients at risk of cognitive impairment and warrant consideration for inclusion in treatment trials.