Immunoinflammatory Response Research Articles

Sleeve Gastrectomy and Gastric Bypass Impact in Patient's Metabolic, Gut Microbiome, and Immuno-inflammatory Profiles-A Comparative Study.

Bariatric surgery is the most long-term effective treatment option for severe obesity. The role of gut microbiome (GM) in either the development of obesity or in response to obesity management strategies has been a matter of debate. This study aims to compare the impact of two of the most popular procedures, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (GB), on metabolic syndrome parameters and gut bacterial microbiome and in systemic immuno-inflammatory response. A prospective observational study enrolled 24 patients with severe obesity, 14 underwent SG and 10GB. Evaluations before (0M) and 6months (6M) after surgical procedures included clinical and biochemical parameters, expression of 17 immuno-inflammatory genes in peripheral blood leukocytes, and assessment of gut microbiome profile using 16s rRNA next-generation sequencing approach. Statistical significance was set to a p value < 0.05 with an FDR < 0.1. A significant and similar decrease in weight-associated parameters and for most metabolic markers was achieved with both surgeries. Considering the gut microbiome in the whole study population, there was an increase in alpha diversity at family-level taxa. Beta diversity between SG and GB at 6M showed near significant differences (p = 0.042) at genus levels. Analysis of the relative abundance of individual taxonomic groups highlighted differences between pre- and post-surgical treatment and between both approaches, namely, a higher representation of family Enterobacteriaceae and genera Veillonella and Enterobacteriaceae_unclassified after GB. Increased expression of immune-inflammatory genes was observed mainly for SG patients. We conclude that SG and GB have similar clinical and metabolic outcomes but different impacts in the gut bacterial microbiome. Results also suggest reactivation of immune response after bariatric surgery.

Immunomodulatory effect of selective COX-2 inhibitor celecoxib on the neuropathological disorders and immunoinflammatory response induced by Kaliotoxin from Androctonus australis venom.

The immune response is increasingly being linked to the pathogenic processes underlying neurological disorders including potassium channel malfunction. Few investigations, meanwhile, have shown how cyclooxygenase-2 (COX-2) is involved in the neuroimmunopathology linked to potassium channel failure. Thus, using an animal model of neuropathology caused by kaliotoxin, an exclusive blocker of voltage-gated potassium channels from the scorpion venom of Androctonus australis hector, we examined the immunomodulatory impact of celecoxib (selective inhibitor of COX-2). The neural and systemic pathogenic effects of KTX can be considerably reduced by celecoxib-mediated COX-2 inhibition, according to the results. It most certainly works via controlling the immunoinflammatory exposure by raising IL-10 levels; decreasing proinflammatory cytokine levels including mostly TNFα and IL-6, and balancing oxidative status. Along with that, by significantly promoting tissue healing, COX-2 inhibitor also enhances cellular metabolism. One potential treatment approach for immunoinflammatory exacerbations linked to neurodegenerative is the COX-2 inhibitor.

Influence of the Gut Microbiota, Metabolism and Environment on Neuropsychiatric Disorders.

The two-way communication between intestinal microbiota and the central nervous system (the microbiota-gut-brain axis) is involved in the regulation of brain function, neurodevelopment, and aging. The microbiota-gut-brain axis dysfunction may be a predisposition factor for Parkinson's disease (PD), Alzheimer's disease (AD), Autism spectrum disorder (ASD), and other neurological diseases. However, it is not clear whether gut microbiota dysfunction contributes to neuropsychiatric disorders. Changes in the gut microbiota may modulate or modify the effects of environmental factors on neuropsychiatric disorders. Factors that impact neuropsychiatric disorders also influence the gut microbiota, including diet patterns, exercise, stress and functional gastrointestinal disorders. These factors change microbiome composition and function, along with the metabolism and immune responses that cause neuropsychiatric disorders. In this review, we summarized epidemiological and laboratory evidence for the influence of the gut microbiota, metabolism and environmental factors on neuropsychiatric disorders incidence and outcomes. Furthermore, the role of gut microbiota in the two-way interaction between the gut and the brain was also reviewed, including the vagus nerve, microbial metabolism, and immuno-inflammatory responses. We also considered the therapeutic strategies that target gut microbiota in the treatment of neuropsychiatric disorders, including prebiotics, probiotics, Fecal microbiota transplant (FMT), and antibiotics. Based on these data, possible strategies for microbiota-targeted intervention could improve people's lives and prevent neuropsychiatric disorders in the future.

ASGR1 deficiency improves atherosclerosis but alters liver metabolism in ApoE-/- mice

The asialoglycoprotein receptor 1 (ASGR1), a multivalent carbohydrate-binding receptor that primarily is responsible for recognizing and eliminating circulating glycoproteins with exposed galactose (Gal) or N-acetylgalactosamine (GalNAc) as terminal glycan residues, has been implicated in modulating the lipid metabolism and reducing cardiovascular disease burden. In this study, we investigated the impact of ASGR1 deficiency (ASGR1−/−) on atherosclerosis by evaluating its effects on plaque formation, lipid metabolism, circulating immunoinflammatory response, and circulating N-glycome under the hypercholesterolemic condition in ApoE-deficient mice. After 16 weeks of a western-type diet, ApoE−/−/ASGR1−/− mice presented lower plasma cholesterol and triglyceride levels compared to ApoE−/−. This was associated with reduced atherosclerotic plaque area and necrotic core formation. Interestingly, ApoE−/−/ASGR1−/− mice showed increased levels of circulating immune cells, increased AST/ALT ratio, and no changes in the N-glycome profile and liver morphology. The liver of ApoE−/−/ASGR1−/− mice, however, presented alterations in the metabolism of lipids, xenobiotics, and bile secretion, indicating broader alterations in liver homeostasis beyond lipids. These data suggest that improvements in circulating lipid metabolism and atherosclerosis in ASGR1 deficiency is paralleled by a deterioration of liver injury. These findings point to the need for additional evaluation before considering ASGR1 as a pharmacological target for dyslipidemia and cardiovascular disorders.Graphical abstract

Abstract 170: A Correlation Between Intracranial Aneurysm and Immunoinflammatory Status with the Imaging Characteristics of Periodontitis

IIntroduction/Purpose Intracranial aneurysms (IAs) are abnormal vascular dilations that often result in severe intracranial bleeding, contributing to morbidity and mortality worldwide. It is believed that IA development, growth, and rupture originate from endothelial dysfunction. A high prevalence of periodontal diseases (PDs) has been linked to both unruptured and ruptured IAs, suggesting that PDs‐associated bacterial invasion, followed by a local immunoinflammatory response, may play a role in IA formation. However, the pathophysiological link between PDs and IAs remains unclear. While some studies have explored the association between PDs and IAs, the relationship between imaging findings suggestive of periodontitis and the status of IAs has not been adequately examined. This study aims to correlate imaging manifestations suggestive of periodontitis with the immunoinflammatory status and aneurysm characteristics in patients with both ruptured and unruptured IAs. Materials and Methods A cross‐sectional study was conducted, classifying patients with IAs and controls (no aneurysms) into six subgroups: 1) Control group, 2) Stable aneurysms, 3) Previously unruptured, currently unruptured treated aneurysms, 4) Previously ruptured, currently unruptured treated aneurysms, 5) Previously unruptured, currently ruptured aneurysms, and 6) Previously ruptured, currently ruptured aneurysms. Computerized Tomography (CT) scans were acquired to evaluate teeth and adjacent alveolar bone for signs of PD. All CT scans were evaluated by a trained dentist. Saliva samples were collected and analyzed for inflammatory markers (e.g., IL‐1β, IL‐6, TNF‐α) and periodontopathic microorganisms. Peripheral blood samples from all groups, and intra‐aneurysmal blood from Groups 3‐6, were collected and analyzed for inflammatory biomarkers and microorganisms. Results This study is a subanalysis of the DentIA study, focusing on periodontal imaging findings in patients with and without IAs. The prevalence and severity of PD markers, such as alveolar bone loss and periodontal pocket, will be analyzed across different patient subgroups. The correlation between the quantity and severity of alveolar bone loss, suggestive of periodontitis, detected on CT and elevated immunoinflammatory biomarkers in saliva, peripheral blood, and intra‐aneurysmal blood will be examined. The levels of IL‐1β, IL‐6, and TNF‐α will be compared amongst patients, stratifying by degree of alveolar bone loss. Additionally, the presence of periodontopathic microorganisms, particularly Porphyromonas gingivalis and Treponema denticola , will be analyzed in patients with and without identifiable aneurysms. Furthermore, extensive alveolar bone loss on imaging will be compared among patients with IAs, evaluating the prevalence and association in patients with advanced aneurysm status, whether in terms of growth, previous rupture, or post‐treatment recurrence. These results may further clarify the potential connection between oral health and the immunoinflammatory environment conducive to aneurysm development and progression. Conclusion This study will provide a detailed analysis of the relationship between IA status, immunoinflammatory biomarkers, and CT imaging characteristics of periodontitis. These preliminary results will indicate how the CT images suggestive of periodontitis are correlated with immunoinflammatory biomarkers in patients with IAs, discussing the potential association between periodontitis imaging characteristics and the presence of IAs, in addition to an elevated immunoinflammatory and periodontopathogenic profile.

Quantitative proteomics and multi-omics analysis identifies potential biomarkers and the underlying pathological molecular networks in Chinese patients with multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj < 0.05). However, they were negatively correlated with the amounts of other metabolites such as L-tyrosine and sphingosine 1-phosphate, as well as the concentrations of IL-8 and MIP-1α. This study outlined the underlying multi-omics integrated mechanisms that might regulate peripheral immunoinflammatory responses and MS progression. These findings are potentially helpful for developing new assisting diagnostic biomarker and therapeutic strategies for MS.

Quorum Sensing Molecule Autoinducer-2 Promotes Macrophage Classical Polarization and Exacerbates Periodontal Inflammation Via Nf-Κb Signalling.

The role of quorum sensing signaling in the immunoinflammatory response during the development of periodontitis is not yet known. This study aimed to explore the effect of Autoinducer-2, a quorum sensing signaling molecule, on macrophage phenotypic remodeling in the immune microenvironment of periodontitis, to further elucidate its mechanism and to discover inhibitors against periodontitis. Bioluminescence experiments and periodontitis model were used to demonstrate the association between periodontitis progression with AI-2. Next, AI-2 challenged macrophage was introduced to transcriptomic sequence and the immune profile was characterized in combination with flow cytometry, qPCR, and immunofluorescence. Activation of NF-κB signalling by AI-2 was confirmed by fluorescence co-localization and immunoblotting. Finally, morphological methods such as Micro-CT and HE, TRAP staining and immunological methods such as immunohistochemistry/fluorescence staining were used to assess the mechanisms by which AI-2 regulates periodontitis progression. AI-2 level was positively correlated with the progression of periodontitis stages and was significantly higher in periodontitis stage III and IV patients. AI-2 promotes macrophage classical polarization and facilitates the secretion of inflammatory factors in vitro, which is dependent on the activation of the NF-κB signaling pathway. AI-2 promotes alveolar bone resorption, but D-ribose acts as a quorum sensing inhibitor to alleviate macrophage classical polarization and attenuates alveolar bone resorption and inflammatory responses in periodontitis mice. Our study demonstrates that AI-2 promoted classical polarization of macrophage and exacerbated periodontal inflammation which could be reversed by D-ribose.

Taiwan Chingguan Yihau may improve post-COVID-19 respiratory complications through PI3K/AKT, HIF-1, and TNF signaling pathways revealed by network pharmacology analysis.

The emergence of new SARS-CoV-2 variants with a higher contagious capability and faster transmissible speed has imposed an incessant menace on global health and the economy. The SARS-CoV-2 infection might reoccur and last much longer than expected. Thence, there is a high possibility that COVID-19 can cause long-term health problems. This condition needs to be investigated thoroughly, especially the post-COVID-19 complications. Respiratory tract disorders are common and typical complications after recovery. Until now, there has been a lack of data on specialized therapeutic medicine for post-COVID-19 complications. The clinical efficacy of NRICM101 has been demonstrated in hospitalized COVID-19 patients. This herbal medicine may also be a promising therapy for post-COVID-19 complications, thanks to its phytochemical constituents. The potential pharmacological mechanisms of NRICM101 in treating post-COVID-19 respiratory complications were investigated using network pharmacology combined with molecular docking, and the results revealed that NRICM101 may exert a beneficial effect through the three primary pathways: PI3K/AKT, HIF-1, and TNF signaling pathways. Flavonoids (especially quercetin) have a predominant role and synergize with other active compounds to produce therapeutic effectiveness. Most of the main active compounds exist in three chief herbal ingredients, including Liquorice root (Glycyrrhiza glabra), Scutellaria root (Scutellaria baicalensis), and Mulberry leaf (Morus alba). To our knowledge, this is the first study of the NRICM101 effect on post-COVID-19 respiratory complications. Our findings may provide a better understanding of the potential mechanisms of NRICM101 in treating SARS-CoV-2 infection and regulating the immunoinflammatory response to improve post-COVID-19 respiratory complications.

First-trimester Doppler Ultrasound for Predicting Successful Management of Pregnancy with Recurrent Pregnancy Losses Due to Antiphospholipid Syndrome and Thrombophilia: A Cohort Study.

Recurrent pregnancy loss (RPL) often stems from a hypercoagulable state that exacerbates conditions such as antiphospholipid syndrome (APS) and thrombophilia, leading to early placental issues. Although treatments such as low-molecular-weight heparin (LMWH) and low-dose aspirin (LDA) are used, outcomes vary. This study proposes using first-trimester Doppler ultrasound - specifically, uterine radial artery resistance index (URa-RI) at 8 weeks and uterine artery pulsatility index (Ut-PI) with pre-diastolic notching (Ut-notch) at 11-13 weeks - to better predict successful pregnancies and reduce risks of adverse outcomes. The aim of this study was to evaluate URa-RI, Ut-PI and Ut-notch between successful pregnancy and not successful and between pregnancy with adverse events and without. The study was conducted in a clinical setting, using a retrospective cohort design on a sample of 72 patients with a history of two or more RPL episodes. Data on URa-RI measured at 8 weeks and Ut-PI and Ut-notch measured at 11-13 weeks were collected. Maternal characteristics - including age, BMI, number of pregnancy losses, etiopathology and immuno-inflammatory response - were considered in the analysis. Comparative statistical analysis was performed on URa-RI, Ut-PI and Ut-notch data, evaluating their associations with pregnancy success and adverse outcomes. Variables were statistically compared between successful and unsuccessful pregnancies and also analysed for adverse events. Analysis was performed using SPSS (IBM, 27th edition). Chi-square tests were applied to nominal categories and multivariate logistic regression adjusted for age, body mass index (BMI), previous pregnancy losses, etiopathology and antinuclear antibody positivity. Primary outcomes (URa-RI, Ut-PI and Ut-notch) were reported with odds ratios and 95% confidence intervals (CIs). Low URa-RI (<0.45) at 8 weeks gives a 16.4 times higher chance for the management to be successful and result in a healthy take-home baby (95% CI = 4.4-61, P < 0.0001). The mean URa-RI was also significantly higher in unsuccessful pregnancy (0.50 ± 0.09 vs. 0.38 ± 0.04, P < 0.0001). High Ut-PI and positive Ut-notch result in a significant increase of adverse event risk, which are 19.4 times and 8.1 times, respectively (95% CI = 4.2-51.6 and 3.12-20.5, P < 0.0001). This study demonstrates the utility of first-trimester Doppler ultrasound (URa-RI, Ut-PI and Ut-notch) in predicting pregnancy success and adverse events in patients with RPL, particularly those managed with LMWH and LDA. These ultrasound markers may provide valuable guidance in managing and anticipating outcomes in RPL cases related to thrombophilia and APS.

Why is it necessary to screen for periodontal disease in diabetic patients?

Periodontal diseases include gingivitis (inflammation of gingiva caused by the bacterial biofilm) and periodontitis involving loss of the supporting structures around the teeth, respectively cementum, periodontal ligament and alveolar bone. Diabetes increases the risk of periodontal diseases; the plausible mechanisms are: alterations in the immunoinflammatory response of bacteria, increased bone loss, the decrease in matrix-producing cells to maintain the periodontium, microvascular changes and alteration in collagen synthesis and metabolism. Treatment of periodontitis influence glycemic control in diabetic patients and intervention trial suggests that this can generate a reduction of circulating inflammatory markers and improves metabolic control in diabetic patients. International forums recommend oral examination as a component of medical care for diabetic patients. Our review summarizes current information on the association of diabetes with periodontal disease.

A Comparative Study of the Aggregate Index of Systemic Inflammation (AISI) and C-Reactive Protein (CRP) in Predicting Odontogenic Abscesses Severity: A Novel Approach to Assessing Immunoinflammatory Response

Background/Objectives: Odontogenic abscesses are a common cause of emergency visits to oral and maxillofacial surgery departments and can lead to life-threatening complications if they are not recognized and treated promptly. The aim of this study was to evaluate the prognostic value of the Aggregate Index of Systemic Inflammation (AISI) in comparison to other systemic inflammatory indices, including the Systemic Immune Inflammation Index (SII), the Neutrophil-to-Lymphocyte Ratio (NLR), the Platelet-to-Lymphocyte Ratio (PLR), and the Lymphocyte-to-Monocyte Ratio (LMR), in predicting the severity of odontogenic abscesses. Methods: This retrospective study included 221 patients hospitalized for odontogenic abscesses at Dubrava University Hospital between January 2019 and December 2023. Clinical and laboratory data, including AISI, SII, NLR, PLR, and LMR, were collected. The severity of the abscesses was assessed using the Symptom Severity (SS) Score and patients were categorized into less severe and severe groups based on their scores. An ROC curve analysis was used to assess the predictive accuracy of each inflammatory index. Results: The AISI was identified as the most effective predictor of abscess severity and had the highest sensitivity (SE = 82.93) and specificity (SP = 81.63) among the indices analyzed. It outperformed C-reactive protein (CRP) in predicting severe abscesses with an AUC of 0.90 compared to 0.74 for CRP. In addition, AISI showed significant correlations with length of hospital stay and the occurrence of systemic inflammatory response syndrome (SIRS). Conclusions: The AISI index is a better predictor of odontogenic abscess severity compared to other systemic inflammatory markers and CRP. Its integration into clinical practice could improve the early detection of high-risk patients, leading to better treatment outcomes and lower risks of complications.

Lysosomes in the immunometabolic reprogramming of immune cells in atherosclerosis.

Lysosomes have a central role in the disposal of extracellular and intracellular cargo and also function as metabolic sensors and signalling platforms in the immunometabolic reprogramming of macrophages and other immune cells in atherosclerosis. Lysosomes can rapidly sense the presence of nutrients within immune cells, thereby switching from catabolism of extracellular material to the recycling of intracellular cargo. Such a fine-tuned degradative response supports the generation of metabolic building blocks through effectors such as mTORC1 or TFEB. By coupling nutrients to downstream signalling and metabolism, lysosomes serve as a crucial hub for cellular function in innate and adaptive immune cells. Lysosomal dysfunction is now recognized to be a hallmark of atherogenesis. Perturbations in nutrient-sensing and signalling have profound effects on the capacity of immune cells to handle cholesterol, perform phagocytosis and efferocytosis, and limit the activation of theinflammasome and other inflammatory pathways. Strategies to improve lysosomal function hold promise as novel modulators of the immunoinflammatory response associated with atherosclerosis. In this Review, we describe the crosstalk between lysosomal biology and immune cell function and polarization, with a particular focus on cellular immunometabolic reprogramming in the context of atherosclerosis.

Impact of Comorbid Pathology and Severity of Clinical Course on Anti-infective Protection in Patients with COVID-19

Objective — to establish and evaluate the impact of comorbid pathology and the severity of the clinical course on the activity of anti-infective protection in patients with coronavirus disease 2019 (COVID-19), based on the analysis of the absolute and relative counts of major immune cell populations in peripheral blood. Materials and methods. A cross-sectional prospective study was conducted involving 204 patients with COVID-19-associated pneumonia of mild, moderate and severe stages. The cohort included 106 (51.97 %) women and 98 (48.03 %) men, with an average age of (55.93 ± 8.75) years. Anti-infective ­protection was studied using comprehensive clinical blood analysis, including the count of major immune-competent cells. Patients were categorised into groups based on comorbi­dity, taking into account the predominant concurrent pathology at the time of examination (endocrine, cardiovascular or other). Results and discussion. More severe COVID-19 cases were characterised by leukopenia, relative and absolute granulocytopenia, neutropenia, a slight hyporegenerative nuclear shift to the right and a reduction in the number of segmented neutrophils by 24.63—34.72 % (p ≤ 0.047—0.009) and eosinophilic granulocytes by 52.94—70.59 % (p ≤ 0.004—0.001). This was accompanied by relative and absolute agranulocytosis due to lymphocytosis (by 20.10—63.33 %; p ≤ 0.05—0.003) and monocytosis (by 40.0—74.12 %; p ≤ 0.046—0.049), indicating an active inflammatory infectious process of viral etiology against a background of decreased resistance and increased activity of the lymphocyte-macrophage link with the beginning of the formation of specific immune protection (cellular and humoral response to coronavirus intervention). Mild cases of COVID-19 showed a higher absolute count of peripheral blood granulocytes (by 48.25 %; p = 0.018), neutrophils, particularly segmented neutrophils and eosinophilic granulocytes, compared to moderate and severe cases (by 32.36—53.18 % (p ≤ 0.049—0.01) and 3.4 times (p ≤ 0.005—0.002)) and the lowest content of monocytes (by 35.41—42.57 %; p ≤ 0.049—0.046). In cases with concurrent endocrine and cardiological pathologies against a background of a more severe clinical course of COVID-19, immunoinflammatory changes intensified due to absolute and relative leukopenia, neutrophilic granulocytopenia, neutropenia, with the presence of relative lymphocytosis and monocytosis, and normal ESR indicators, confirming the inflammatory process of viral etiology, which, in the absence of treatment, may tend to form post-COVID and/or long-term effects of COVID-19 with multisystem involvement. Conclusions. The study found an enhancement of the immunoinflammatory response and an increase in the depletion of cellular factors of non-specific anti-infective protection with the progression of the clinical manifestations of COVID-19, particularly against the backdrop of comorbid endocrine and/or cardiological pathology.

Activity-based anorexia (ABA) model: Effects on brain neuroinflammation, redox balance and neuroplasticity during the acute phase

Several evidences suggest that immuno-inflammatory responses are involved in the pathogenesis of anorexia nervosa (AN). Herein we investigate the possible alteration of key mediators of inflammation, redox balance, and neuroplasticity in the brain of rats showing an anorexic-like phenotype. We modeled AN in adolescent female rats using the activity-based anorexia (ABA) paradigm and measured gene expression levels of targets of interest in the prefrontal cortex (PFC) and dorsal hippocampus (DH). We observed reduced mRNA levels of pro-inflammatory cytokines IL-1β and TNF-α, the inflammasome NLRP3, and the microglial marker CD11b in both PFC and DH of ABA animals. Conversely, the mRNA of IL-6, which acts as both a pro-inflammatory and anti-inflammatory cytokine, was increased. Moreover, we observed an overall upregulation of different antioxidant enzymes in PFC, while their profile was not affected or opposite in the DH, with the exception of MT1α. Interestingly, ABA animals showed elevated levels of the neuroplasticity marker BDNF in both PFC and DH. Our data indicate that ABA induction is associated with anatomical-specific cerebral alteration of mediators of neuroinflammation, oxidative balance and neuroplasticity. Although more research should be conducted, these results add important information about the role of these systems in the complex AN etiopathogenesis.

Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women

BackgroundPeriodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials.MethodsWe collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women.ResultsWe demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride.ConclusionsThe current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.

Hydrophilic Components as Key Active Ingredients in Adipose-Derived Matrix Bioscaffolds for Inducing Fat Regeneration.

Decellularized adipose-derived matrix (DAM) has emerged as a promising biomaterial for soft tissue reconstruction. However, due to a lack of research on its complex composition, the understanding of the key components in DAM remains limited, leading to inconsistent adipogenic properties and challenges in optimizing preparation methods purposefully. In this study, it is proposed for the first time that DAM comprises two distinct components: hydrophilic (H-DAM) and lipophilic (L-DAM), each with markedly different effects on fat regeneration. It is confirmed that H-DAM is the key component for inducing fat regeneration due to its enhanced cell-cell and cell-scaffold interactions, primarily mediated by the Hedgehog signaling pathway. In contrast, L-DAM exhibits poor cell adhesion and contains more antigenic components, leading to a higher immunoinflammatory response and reduced adipogenesis. In addition, it is found that intracellular proteins, which are more abundant in H-DAM, can be retained as beneficial components due to their hydrophilicity, contrary to the conventional view that they shall be removed. Accordingly, a purified bioscaffold with unprecedented efficacy is proposed for fat regeneration and reduced immunogenicity. This finding provides insights for developing scaffolds for fat regeneration and promotes the realization of xenotransplantation.

Microplastics are associated with elevated atherosclerotic risk and increased vascular complexity in acute coronary syndrome patients

BackgroundMicroplastics, widely present in the environment, are implicated in disease pathogenesis through oxidative stress and immune modulation. Prevailing research, primarily based on animal and cell studies, falls short in elucidating microplastics' impact on human cardiovascular health. This cross-sectional study detected blood microplastic concentrations in patients presenting with chest pain using pyrolysis–gas chromatography/mass spectrometry and evaluating inflammatory and immune markers through flow cytometry, to explore the potential effects of microplastic on acute coronary syndrome.ResultsThe study included 101 participants, comprising 19 controls and 82 acute coronary syndrome cases. Notably, acute coronary syndrome patients exhibited elevated microplastic concentrations, with those suffering from acute myocardial infarction presenting higher loads compared to those with unstable angina. Furthermore, patients at intermediate to high risk of coronary artery disease displayed significantly higher microplastic accumulations than their low-risk counterparts. A significant relationship was observed between increased microplastic levels and enhanced IL-6 and IL-12p70 contents, alongside elevated B lymphocyte and natural killer cell counts.ConclusionThese results suggest an association between microplastics and both vascular pathology complexity and immunoinflammatory response in acute coronary syndrome, underscoring the critical need for targeted research to delineate the mechanisms of this association.HighlightsBlood microplastic levels escalate from angiographic patency, to angina patients, peaking in myocardial infarction patients.Microplastics in acute coronary syndrome patients are predominantly PE, followed by PVC, PS, and PP.Microplastics may induce immune cell-associated inflammatory responses in acute coronary syndrome patients.Graphical abstract

The microbial damage and host response framework: lesson learned from pathogenic survival trajectories and immunoinflammatory responses of Talaromyces marneffei infection.

The adverse outcomes of fungal infection in mammalian hosts depend on the complex interactions between the host immune system and pathogen virulence-associated traits. The main clinical problems arise when the host response is either too weak to effectively eliminate the pathogen or overly aggressive, resulting in host tissue damage rather than protection. This article will highlight current knowledge regarding the virulence attributions and mechanisms involved in the dual-sided role of the host immune system in the immunopathogenesis of the thermally dimorphic fungus Talaromyces marneffei through the lens of the damage response framework (DRF) of microbial pathogenesis model.

Zingiber officinale Roscoe extract improves nigrostriatal dopaminergic activity in rotenone-induced Parkinsonian mice: Implication of COX-2/TNF-α/IL-6 and antioxidant enzyme crosstalk in the immunoinflammatory responses

Ethnopharmacological relevanceParkinson's disease (PD) is a chronic neurodegenerative disease that occurs progressively with time. Current PD treatments are symptomatic with moderate effects on striatal dopamine release. Previously, the ethnomedicinal benefits of Zingiber officinale Roscoe have been demonstrated to possess a broad range of pharmacological benefits, but no single data on its effect against nigrostriatal degeneration in PD model has been reported. AimProactive neuroprotective and pharmacotherapeutic approaches with asymptomatic effects are needed to prevent the progression of Parkinson's disease (PD) and maintain the appropriate population of dopaminergic neurons. Current treatments are symptomatic and can only elevate the striatal dopamine levels. Hence, the objective of the study is to elucidate the neuroprotective and neurorestorative properties of Zingiber officinale methanol extract (MEZO) on nigrostriatal degeneration implicated by immunoinflammatory responses in rotenone-challenged PD mice model. MethodsMale Swiss mice were injected with rotenone (2.5 mg/kg) intraperitoneally to induce PD symptoms 30 minutes prior to MEZO (50 and 100 mg/kg) and LD-CD (10 mg/kg) oral treatment for 28 days. Motor/neuromuscular behavior, dopamine, acetylcholinesterase (AChE), tyrosine hydroxylase (TH), α-synuclein (α-syn), cyclooxygenase-2 (COX-2), oxidative stress markers, inflammatory cytokines, and histopathology were evaluated. ResultsOur data showed that MEZO treatment attenuated sensorimotor and neuromuscular incompetence by up-regulating the expression of TH protein and dopamine release and maintaining AChE enzyme in the symptomatic mice. We observed that MEZO treatment prevented the formation of Lewis bodies (LBs) by inhibiting the aggregation of nigrostriatal α-Syn proteins, decreasing the release of pro-oxidant and pro-inflammatory mediators and cyclooxygenase-2 (COX-2) protein expression, increasing glutathione enzymes, and moderately abated the loss dopaminergic neurons in a dose-dependent effect in the symptomatic mice. ConclusionThese findings demonstrated that MEZO exhibited the potential neuroprotective and neurorestorative effect in the treatment and management of PD.

Porphyromonas gingivalis persisters induce the immuno-inflammatory responses in macrophages by upregulating the forkhead box1 signaling pathway

Objective: To investigate the effects of Porphyromonas gingivalis (Pg) persisters (Ps) on immuno-inflammatory responses in macrophages, and to explore the underlying mechanisms. Methods: Pg cells were cultured to the stationary phase (72 h), and subsequently treated by high concentration of metronidazole at 100 mg/L, amoxicillin at 100 mg/L and the combination of them for different time period, named as metronidazole group, amoxicillin group and (metronidazole+amoxicillin) group. Pg cells without treatment were used as Blank control. The survival profile of PgPs cells was measured by colony-forming unit assay. The living state of PgPs was observed by Live/Dead staining. Then, Pg and metronidazole-treated PgPs (M-PgPs) were used to treat macrophages, named as Pg group and M-PgPs group. Transmission electron microscopy (TEM) was used to observe the bacteria in the macrophages. The expression levels of proinflammatory cytokines in macrophages were determined by real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay. The location of forkhead box transcription factor 1 (FOXO1) was detected by confocal immunofluorescence microscopy. After inhibiting or enhancing the FOXO1 expressions using inhibitors (Fi) or activators (Fa) respectively, the macrophages were treated with Pg and M-PgPs, divided as Blank group, Pg group, M-PgPs group, Fi group, (Fi+Pg) group, (Fi+M-PgPs) group, Fa group, (Fa+Pg) group and (Fa+M-PgPs) group. Then, the expression pattens of proinflammatory cytokines were assessed. Results: Remarkable number of lived PgPs was observed, both in planktonic culture and Pg biofilms either treated with metronidazole, amoxicillin or both, and those persisters could form new colonies. Pg and M-PgPs were able to enter into the macrophages and the protein expression levels of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) [Pg group: (2 392±188), (162±29), (5 558±661), (789±155) μg/L; M-PgPs group: (2 415±420), (155±3), (5 732±782), (821±176) μg/L] were significantly upregulated than those in Blank group [(485±140), (21±9), (2 332±87), (77±7) μg/L] (P<0.01). Moreover, Pg and M-PgPs could facilitate the nuclear translocation and accumulation of FOXO1. In addition, the relative mRNA expression levels of FOXO1, B-cell lymphoma 6 and Krüppel-like factor 2 were upregulated when compared to Blank group (P<0.05). Furthermore, the protein expression levels of IL-1β, IL-6, IL-8 and TNF-α in Fi+Pg group [(1 081±168), (70±8), (1 976±544), (420±47) μg/L] were remarkably lower than Pg group [(4 411±137), (179±6), (5 161±929), (934±24) μg/L] (P<0.05). Similarly, the protein expression levels of IL-1β, IL-6, IL-8 and TNF-α in Fi+M-PgPs group [(1 032±237), (74±10), (1 861±614), (405±32) μg/L] were remarkably lower than M-PgPs group [(4 342±314), (164±17), (4 438±1 374), (957±25) μg/L] (P<0.05). On the contrary, the protein expression levels of IL-1β, IL-6, IL-8 and TNF-α in Fa+Pg group [(8 198±1 825), (431±28), (8 919±650), (2 186±301) μg/L] and Fa+M-PgPs group [(8 159±2 627), (475±26), (8 995±653), (2 255±387) μg/L] were significantly higher than Pg group and M-PgPs group, respectively (P<0.05). Conclusions: PgPs are highly tolerant to metronidazole and amoxicillin. The M-PgPs could enhance the immuno-inflammatory responses in macrophages by upregulating the FOXO1 signaling pathway, while this effect exhibits no significant difference with Pg.