Immunoinflammatory Response Research Articles

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.

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.

Global research states and trends of micro RNA in irritable bowel syndrome: a bibliometric analysis

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, but its diagnosis and treatment remain obscure. Non-coding RNAs (ncRNAs), as potential biomarkers, have attracted increasing attention in digestive diseases. Here, we present a comprehensive research status, development trends, and valuable insights in this subject area. The literature search was performed using Web of Science Core Collection. VOSviewer 1.6.20, Citespace 6.2.R4, and Microsoft Excel 2021 were used for bibliometric analysis. A total of 124 articles were included in the analysis. Overall, publication patterns fluctuated. Globally, People’s Republic of China, the USA, and Germany were the top three contributors of publications. Guangzhou University of Chinese Medicine, University of California, Mayo Clinic, and University of California, Los Angeles contributed the highest number of publications. The pathways and specific mechanisms by which ncRNAs regulate transcription and translation and thus regulate the pathophysiological processes of IBS are the main research hotspots in this field. We found that microRNA (miRNAs) are intricately involved in the regulation of key pathologies such as viscera sensitivity, intestinal permeability, intestinal mucosal barrier, immunoinflammatory response, and brain-gut axis in the IBS, and these topics have garnered significant attention in research community. Notably, microecological disorders are also associated with IBS pathogenesis, and ncRNA may play an important role in the interactions between host and intestinal flora. This is the first bibliometric study to comprehensively summarize the research hotspots and trends related to IBS and ncRNAs (especially miRNAs). Our findings will help understand the role of ncRNAs in IBS and provide guidance to future studies.

The Association of Pretreatment Systemic Immune Inflammatory Response Index (SII) and Neutrophil-to-Lymphocyte Ratio (NLR) with Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma.

Immunoinflammatory response can participate in the development of cancer. To investigate the relationship between pretreatment systemic immune inflammatory response index (SII), systemic inflammatory response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and lymph node metastasis in patients with papillary thyroid carcinoma (PTC). A retrospective analysis was performed on 547 PTC patients treated in Meizhou People's Hospital from January 2018 to December 2021. Clinicopathological data were collected, including gender, age, Hashimoto's thyroiditis, maximum tumor diameter, extra-membrane infiltration, disease stage, BRAF V600E mutation, pretreatment inflammatory index levels, and lymph node metastasis. The optimal cutoff values of SII, SIRI, NLR, PLR and LMR were calculated by receiver operating characteristic (ROC) curve, and the relationship between inflammatory indexes and other clinicopathological features and lymph node metastasis was analyzed. There were 303 (55.4%) PTC patients with lymph node metastasis. The levels of SII, SIRI, NLR, and PLR in patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis, while the levels of LMR were significantly lower than those in patients without lymph node metastasis (all p<0.05). When lymph node metastasis was taken as the endpoint, the critical value of SII was 625.375, the SIRI cutoff value was 0.705, the NLR cutoff value was 1.915 (all area under the ROC curve >0.6). The results of regression logistic analysis showed that age <55 years old (OR: 1.626, 95% CI: 1.009-2.623, p=0.046), maximum tumor diameter >1cm (OR: 2.681, 95% CI: 1.819-3.952, p<0.001), BRAF V600E mutation (OR: 2.709, 95% CI: 1.542-4.759, p=0.001), SII positive (≥625.375/<625.375, OR: 2.663, 95% CI: 1.560-4.546, p<0.001), and NLR positive (≥1.915/<1.915, OR: 1.808, 95% CI: 1.118-2.923, p=0.016) were independent risk factors for lymph node metastasis of PTC. Age <55 years old, maximum tumor diameter >1cm, BRAF V600E mutation, SII positive, and NLR positive were independent risk factors for lymph node metastasis in PTC.

Immune-mediated disruption of the blood-brain barrier after intracerebral hemorrhage: Insights and potential therapeutic targets.

Intracerebral hemorrhage (ICH) is a condition that arises due to the rupture of cerebral blood vessels, leading to the flow of blood into the brain tissue. One of the pathological alterations that occurs during an acute ICH is an impairment of the blood-brain barrier (BBB), which leads to severe perihematomal edema and an immune response. A complex interplay between the cells of the BBB, for example, pericytes, astrocytes, and brain endothelial cells, with resident and infiltrating immune cells, such as microglia, monocytes, neutrophils, T lymphocytes, and others accounts for both damaging and protective mechanisms at the BBB following ICH. However, the precise immunological influence of BBB disruption has yet to be richly ascertained, especially at various stages of ICH. This review summarizes the changes in different cell types and molecular components of the BBB associated with immune-inflammatory responses during ICH. Furthermore, it highlights promising immunoregulatory therapies to protect the integrity of the BBB after ICH. By offering a comprehensive understanding of the mechanisms behind BBB damage linked to cellular and molecular immunoinflammatory responses after ICH, this article aimed to accelerate the identification of potential therapeutic targets and expedite further translational research.

Neutrophil-to-lymphocyte ratio and red blood cell distribution width to platelet ratio and their relationships with inflammatory and antioxidant status in dogs with different stages of heart failure due to myxomatous mitral valve disease

We aimed to evaluate the red blood cell distribution width-to-platelet ratio (RDW/PLT) with other complete blood cell count (CBC) indices and their correlations with serum proinflammatory cytokines, acute phase proteins (APPs), and antioxidant biomarkers in dogs at different stages of heart failure (HF). A total of 29 dogs were divided into four groups according to the ACVIM Consensus Statement: stage-A (healthy/controls, n = 8), stage-B2 (n = 6), stage-C (n = 10), and stage-D (n = 5). Seventeen CBC indices were calculated and correlated with the measurements of inflammatory, APPs, and antioxidant biomarkers, as well as selected echocardiographic variables in all dogs. At stage-C, CBC indices were evaluated 14 days after the treatment. Statistically significant changes were observed only for RDW/PLT and neutrophil-to-lymphocyte ratio (NLR) between groups. NLR increased, but RDW/PLT deceased in dogs with HF, compared to controls (P < 0.05). There were no statistically differences between pre- and post-treatment CBC indices. There were significantly positive and negative correlations between the CBC indices, serum parameters and selected echocardiographic variables in dogs with HF(P < 0.05). ROC analysis showed the best sensitivity (57% and 68%) and specificity (100% and 57%) for NLR > 5.8 and RDW/PLT ≤ 0.057 for predicting the severity of HF, respectively. Results showed that NLR and RDW/PLT may have potential for monitoring severity of the disease and the effect of treatment in dogs with HF. Imbalances between indices of circulating blood cells can contribute to immunoinflammatory and antioxidant responses in pathogenesis of canine HF, which may provide us alternative targets to develop new diagnostic and therapeutic strategies in veterinary medicine.

A comprehensive analysis of the differential expression in the hippocampus of depression induced by gut microbiota compared to traditional stress

Depression, which is a disease of heterogeneous etiology, is characterized by high disability and mortality rates. Gut microbiota are associated with the development of depression. To further explore any differences in the mechanisms of depression induced by gut microbiota and traditional stresses, as well as facilitate the development of microbiota-based interventions, a fecal microbiota transplantation (FMT) depression model was made. This was achieved by transplanting feces from major depressive disorder (MDD) patients into germ-free mice. Second, the mechanisms of the depression induced by gut microbiota were analyzed in comparison with those of the depression caused by different forms of stress. It turned out that mice exhibited depressive-like behavior after FMT. Then, PCR array analysis was performed on the hippocampus of the depressed mice to identify differentially expressed genes (DEGs). The KEGG analysis revealed that the pathways of depression induced by gut microbes are closely associated with immuno-inflammation. To determine the pathogenic pathways of physiological stress and psychological stress-induced depression, raw data was extracted from several databases and KEGG analysis was performed. The results from the analysis revealed that the mechanisms of depression induced by physiological and psychological stress are closely related to the regulation of neurotransmitters and energy metabolism. Interestingly, the immunoinflammatory response was distinct across different etiologies that induced depression. The findings showed that gut microbiota dysbiosis-induced depression was mainly associated with adaptive immunity, while physiological stress-induced depression was more linked to innate immunity. This study compared the pathogenesis of depression caused by gut microbiota dysbiosis, and physiological and psychological stress. We explored new intervention methods for depression and laid the foundation for precise treatment.

Developmental PFOS exposure alters lung inflammation and barrier integrity in juvenile mice.

Emerging epidemiological evidence indicates perfluorooctane sulfonic acid (PFOS) is increasingly associated with asthma and respiratory viral infections. Animal studies suggest PFOS disrupts lung development and immuno-inflammatory responses, but little is known about the potential consequences on respiratory health and disease risk. Importantly, PFOS exposure during the critical stages of lung development may increase disease risk later in life. Thus, we hypothesized that developmental PFOS exposure will affect lung inflammation and alveolar/airway development in a sex-dependent manner. To address this knowledge gap, timed pregnant Balb/cJ dams were orally dosed with a PFOS (1.0 or 2.0 mg/kg/d) injected mealworm or a vehicle control daily from gestational day (GD) 0.5 to postnatal day (PND) 21, and offspring were sacrificed at PND 22-23. PFOS-exposed male offspring displayed increased alveolar septa thickness. Occludin was also downregulated in the lungs after PFOS exposure in mice, indicative of barrier dysfunction. BALF macrophages were significantly elevated at 2.0 mg/kg/d PFOS in both sexes compared with vehicles, whereas BALF cytokines (TNF-α, IL-6, KC, MIP-1α, MIP-1β, and MCP-1) were suppressed in PFOS-exposed male offspring compared with vehicle controls. Multiplex nucleic acid hybridization assay showed male-specific downregulation of cytokine gene expression in PFOS-exposed mice compared with vehicle mice. Overall, these results demonstrate PFOS exposure exhibits male-specific adverse effects on lung development and inflammation in juvenile offspring, possibly predisposing them to later-in-life respiratory disease. Further research is required to elucidate the mechanisms underlying the sex-differentiated pulmonary toxicity of PFOS.

Myocardial infarction accelerates the progression of MASH by triggering immunoinflammatory response and induction of periostin

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD), especially advanced metabolic dysfunction-associated steatohepatitis (MASH), have an increased risk of cardiovascular diseases (CVDs). Whether CVD events will, in turn, influence the pathogenesis of MASLD remains unknown. Here, we show that myocardial infarction (MI) accelerates hepatic pathological progression of MASLD. Patients with MASLD who experience CVD events after their diagnosis exhibit accelerated liver fibrosis progression. MI promotes hepatic fibrosis in mice with MASH, accompanied by elevated circulating Ly6Chi monocytes and their recruitment to damaged liver tissues. These adverse effects are significantly abrogated when deleting these cells. Meanwhile, MI substantially increases circulating and cardiac periostin levels, which act on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis, finally exacerbating hepatic pathological progression of MASH. These preclinical and clinical results demonstrate that MI alters systemic homeostasis and upregulates pro-fibrotic factor production, triggering cross-disease communication that accelerates hepatic pathological progression of MASLD.

Prognostic value of serum immunoglobulin M levels in patients with acute coronary syndrome

Background and aimsThe immuno-inflammatory response is a crucial early step in the development of acute coronary syndrome (ACS). In this study, we investigated whether immunoglobulin M (IgM) in the body's initial immune response can predict the prognosis of patients with ACS. MethodsThis prospective cohort study enrolled 1556 ACS patients at Beijing Hospital between March 2017 and October 2020. All patients underwent coronary angiography (CAG). The serum IgM concentration and biochemical indicators were evaluated prior to CAG. The primary endpoint was the composite endpoint of major adverse cardiovascular and cerebrovascular events (MACCEs). Multivariate Cox proportional hazards models was used to explore the association between IgM levels and the endpoint. ResultsThe average serum IgM levels of the population was 61.3 (42.6–88.4) mg/dL. During the median follow-up period of 55 months, 150 MACCEs occurred. Kaplan-Meier analysis showed that low serum IgM levels were associated with occurrence of MACCEs (log-rank p = 0.009). Univariate Cox proportional hazards models showed that low serum IgM (≤78.05 mg/dL) was associated with MACCEs (hazard ratio (HR) 1.648, 95 % confidence interval (CI): 1.129–2.406, p = 0.010). In patients with IgM ≤78.05 mg/dL, the HR for partially adjusted MACCEs events was 1.576 (95 % CI: 1.075–2.310) and 1.930 (95 % CI: 1.080–3.449) after adjusting for multiple covariates. The subgroup analysis showed that for patients in ≤24 BMI, never smoking and non-dyslipidemia subgroup, the lower serum IgM levels was significantly associated with the risk of MACCEs (pinteraction < 0.001, pinteraction = 0.037, pinteraction = 0.024, respectively). ConclusionsLow serum IgM levels was independently associated with MACCEs in ACS patients, especially for patients without obesity, smoking and dyslipidemia.