Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3^-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.

Ulcerative colitis (UC) is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental UC. UC was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Some mice received i.v. dose of CT-1 (200 µg/kg) 2 hours before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS. The severity of UC was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before UC induction improves the clinical course, tissue damage and inflammation degree in DSS-induced UC in mice.

Atherosclerosis is a chronic inflammatory disease which results in thickening of the vessel wall and narrowing of the lumen. It is a leading cause of death worldwide. Preventive treatment is taken into prioritized consideration since currently no effective approaches to cure atherosclerosis are available. These treatments mainly focus on lowering blood cholesterol levels, especially LDL-C, by statins. Even so, lowering lipid levels is not sufficient to reduce the risk of cardiovascular events in all patients. Recently, atherosclerosis has increasingly been recognized as a chronic inflammatory disease involving the immune system, initiating new therapeutic approaches which could alleviate or prevent atherosclerosis by modulating inflammation. Mesenchymal stem cells (MSCs) have emerged as a promising option to relieve inflammation and balance immune responses in inflammatory diseases. Several studies including our group also reported that MSCs may be a new therapeutic option for atherosclerosis. This review summarizes the updated state of our knowledge in the administration of MSCs to alleviate atherosclerosis and discusses some of the key unresolved challenges that need to be solved in future studies.

While over half of all spinal cord injuries (SCIs) occur in the cervical region, the majority of preclinical studies have focused on models of thoracic injury. However, these two levels are anatomically distinct—with the cervical region possessing a greater vascular supply, grey-white matter ratio and sympathetic outflow relative to the thoracic region. As such, there exists a significant knowledge gap in the secondary pathology at these levels following SCI. In this study, we characterized the systemic plasma markers of inflammation over time (1, 3, 7, 14, 56 days post-SCI) after moderate-severe, clip-compression cervical and thoracic SCI in the rat. Using high-throughput ELISA panels, we observed a clear level-specific difference in plasma levels of VEGF, leptin, IP10, IL18, GCSF, and fractalkine. Overall, cervical SCI had reduced expressions of both pro- and anti-inflammatory proteins relative to thoracic SCI, likely due to sympathetic dysregulation associated with higher level SCIs. However, contrary to the literature, we did not observe level-dependent splenic atrophy with our incomplete SCI model. This is the first study to compare the systemic plasma-level changes following cervical and thoracic SCI using level-matched and time-matched controls. The results of this study provide the first evidence in support of level-targeted intervention and also challenge the phenomenon of high SCI-induced splenic atrophy in incomplete SCI models.

Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.

1) Background: Keloids occur after the failure during the wound-healing process, persist the inflammation and are refractory to various treatments. The pathogenesis of keloids is still unclear. We previously analyzed the gene expression profiles in keloid tissue using microarray and Northern blot analysis and found that HtrA1 was markedly upregulated in the keloid lesions. HtrA1 is a member of the HtrA family of serine protease, has been suggested to play a role in the pathogenesis of various diseases including age-related macular degeneration and osteoarthritis by modulating proteins in extracellular matrix or cell surface. We focused on HtrA1, analyzed the localization and the role in keloid pathogenesis. 2) Methods: Twenty seven keloid patients and seven unrelated patients were enrolled in this study. We performed in situ hybridization analysis, immunohistochemical analysis, western blot analysis and cell proliferation assay. 3) Results: First, the fibroblast-like cells expressed HtrA1 higher in the active keloid lesions than in the surrounding lesions in situ hybridization. Second, the proportion of HtrA1-positive cells in keloid was higher than that of in normal skin significantly in immunohistochemical analysis. Third, HtrA1 protein was up-regulated, relative to normal skin tissue samples in western blot analysis. Finally, silencing of HtrA1 gene expression suppressed the cell proliferation significantly. 4) Conclusion: HtrA1 was highly expressed in keloid tissues and the suppression of HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development through accelerating cell proliferation and remodeling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.

Autonomous navigation in dynamic environments poses a significant challenge in the field of ro-botics with the primary goals of ensuring both smooth and safe movement. This study introduces control strategy based on an Adaptive Neuro-Fuzzy Inference System (ANFIS) to enhance au-tonomous robot navigation in dynamic environments, emphasizing on collision-free path plan-ning. This strategy employs, a path planning technique to develop a trajectory that allows the ro-bot to navigate smoothly while avoiding collisions with both static and dynamic obstacles. The developed control system incorporates four ANFIS controllers: two are tasked with guiding the robot toward its end point, and the other two are activated for obstacle avoidance. The experi-mental setup conducted in CoppeliaSim involves a mobile robot equipped with ultrasonic sensors navigating in an environment with static and dynamic obstacles. Simulation experiments are conducted to demonstrate the model's capability in ensuring collision-free navigation, employing a path planning algorithm to ascertain the shortest route to the target destination. The simulation results highlight the superiority of the ANFIS-based approach over conventional methods, partic-ularly in terms of computational efficiency and navigational smoothness.

The importance of detecting and diagnosing the imminence of aneurysm rupture before it occurs cannot be overstated. However, this process is often time-consuming and challenging, with variability in conclusions not uncommon among experts. Furthermore, current state-of-the-art models in medical image segmentation suffer from limited availability of large annotated datasets for training, exacerbated by an immense data imbalance. In most segmentation tasks, 3D segmentation is preferred due to its capacity to leverage more contextual information. However, these models require more data, which is constrained by the aforementioned issues. In the realm of current diagnosis models, those lacking geographic context are notably ineffective. To address these issues, the aim is to develop a model pipeline to accurately detect cerebral intracranial aneurysms and diagnose rupture imminence through 3D magnetic resonance angiography (MRA) and tabular input, augmented with the implementation of neuro-symbolic ai. The utilization of data fusion to tackle the lack of context in tabular models is proposed, leveraging extracted geographical features from a segmentation model. To enhance segmentation results and tackle the data imbalance in aneurysm segmentation, a two-stage model pipeline that extracts contextual geographic features before aneurysm segmentation is suggested. Segmentation results are additionally improved through ensemble techniques and novel preprocessing techniques. Finally, a neuro-symbolic aspect is introduced to enhance model diagnosis, interpretability and performance. The multi-step Integrated Neuro-Symbolic Analysis Pipeline for Cerebral Aneurysm Rupture Diagnosis is introduced.

One of the most crucial and economically beneficial tasks for energy customer is peak load curtailment. On account of the fast response of renewable energy resources (RERs) such as photovoltaic (PV) units and battery energy storage system (BESS), this task is closer to be efficiently implemented. Depends on the customer peak load demand and energy characteristics, the feasibility of this strategy may warry. When adaptive neuro-fuzzy inference system (ANFIS) is exploited for forecasting, it can provide many benefits to address the above-mentioned issues and facilitate its easy implementation, with short calculating time and re-trainability. This paper introduces a data driven forecasting method based on fuzzy logic for optimized peak load reduction. First, the amount of energy generated by PV is forecasted using ANFIS which conducts output trend, and then, the BESS capacity is calculated according to the forecasted results. The trend of the load power is then decomposed in Cartesian plane into two parts, left and right from load peak, searching for BESS capacity equal. Network switching sequence over consumption is provided by a fuzzy logic controller (FLC) with respect to BESS capacity and PV energy output. Finally, to prove the effectiveness of the proposed ANFIS-based peak shaving method, offline digital time-domain simulations have been performed on a real-life practical test micro grid system in MATLAB/Simulink environment and the results have been experimentally verified by testing on a practical micro grid system with real-life data obtained from smart meter and also, compared with several previously-reported methods.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and potently attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine secretion, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals.

Due to the manufacturing process of Additive Manufacturing (AM) Parts the mechanical properties cannot be predicted. The scope of the present work is to propose a predictive tool for the mechanical properties of AM parts through the use of Adaptive Neuro-Fuzzy Inference System (ANFIS). The Adaptive Neuro-Fuzzy Inference System (ANFIS) combines neural networks with fuzzy logic to generate a mapping between the inputs and the output. Real data experiments from different AM technologies and materials compose the initial dataset so a detailed investigation is conducted to gain knowledge of how different parameters affect the UTS, the elongation and the Young modulus of each experiment. Experimental data were also use to train, check and verify the methodology. The method is tested for FFF technology, PLA material and 3 point bending stress, with interesting results.

Multiple Sclerosis (MS) is a neurodegenerative disease that mainly affects young adults. The high prevalence of the disease and its impact on patients' quality of life led to priority being given to the etiopathogenesis of the disease to identify possible modifiable factors and consequent effective intervention strategies. Recent hypotheses suggest that the etiopathogenesis of MS is multifactorial and includes factors related to the immune system, neuroinflammation and neuro-degeneration. In this scenario, sleep has a close - although indirect - relationship with MS, through its relationship with each of those factors. In particular, the role of cytokines in immune system impairment and neuroinflammation, mitochondrial dysfunction and oxidative stress in neurodegeneration all are associated with sleep in different forms. Furthermore, melatonin in relation with vitamin D has a potential therapeutic effect in MS sleep-related problems. Given the growing interest of research in the mechanisms underlying MS and therapies able to alleviate MS-related symptoms at all stages of the disease, a more in-depth study of the role of sleep disturbances and the factors intrinsically related to sleep and MS could be useful both to investigate the etiopathogenetic factors of MS and to develop potential non-invasive intervention strategies for MS treatment.

FDG PET has been widely used in oncology studies as well as for cardiovascular diseases. This technique has recently been applied to detect active cardiovascular inflammation, mainly owing to enhanced glucose utilization by the activation of granulocytes and macrophages. To identify active inflammation by FDG PET, physiological uptake in the normal myocardium should be suppressed by appropriate patient preparation. FDG PET has been used to detect active lesions and assess the response to anti-inflammatory therapy in patients with cardiac sarcoidosis. In addition, other active cardiovascular inflammations, such as endocarditis, aortitis, and unstable atherosclerosis may be identified by FDG PET. After cancer treatment, FDG PET is considered an elegant approach not only for the assessment of tumor response to cancer therapy, but also for early detection of possible cardiovascular involvement. This review summarizes the clinical values of FDG PET for the assessment of active cardiovascular inflammation under suitable patient preparation.

Sputum induction (SI) is a non-invasive technique to obtain lower airway samples from people who do not spontaneously produce sputum. Since its introduction in 1958, its use has significantly increased for various respiratory conditions, especially with the establishment of standardized techniques. It has been used in pediatric research since 2002, starting with asthma studies. It is a safe and repeatable procedure for non-expectorating children. The ability to analyze both cellular and fluid components of sputum provides valuable information about lung diseases. This work reviews the utility of sputum induction in pediatric respiratory research and its potential clinical applications. We also discuss the safety, tolerability, and side effects profile of the procedure, emphasizing its significance in pediatric respiratory research. Despite the valuable insights gained from SI studies, challenges remain for widespread clinical utilization, requiring further refinement of the technique and increased accessibility in clinical settings.

3.9 million individuals rely on kidney replacement therapy worldwide. They experience height-ened susceptibility to cardiovascular diseases and mortality, alongside an increased risk of in-fections and malignancies, with inflammation being key to explaining this intensified risk. This study utilized semi-targeted metabolomics to explore novel metabolic pathways related to in-flammation in this populations. We collected pre and post-session blood samples of patients who had already undergone one year of chronic hemodialysis. And used liquid chromatography and high resolution mass spectrometry to perform a metabolomic analysis. Afterwards, we employed both univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regulari-zation) to identify metabolites associated with inflammation. In the univariate analysis, in-dole-3-acetaldehyde, 2-ketobutyric acid, and urocanic acid showed statistically significant de-creases in median concentrations in the presence of inflammation. In the multivariate analysis, metabolites positively associated with inflammation include allantoin, taurodeoxycholic acid, norepinephrine, pyroglutamic acid, and L-hydroorotic acid. Conversely, metabolites showing negative associations with inflammation include benzoic acid, indole-3-acetaldehyde, methio-nine, citrulline, alphaketoglutarate, n-acetyl-ornithine and 3-4-dihydroxibenzeneacetic acid. Non inflamed patients exhibit preserved autophagy and reduced mitochondrial dysfunction. Under-standing inflammation in this group hinges on the metabolism of arginine and the urea cycle. Additionally, the microbiota, particularly uricase-producing bacteria and those metabolizing tryptophan, play critical roles.

Inflammation is the body’s response to infection, injury, or other stimuli. Acute inflammation is a crucial component of the immune system’s defense, aimed at eliminating infected or damaged cells and halting disease progression. A subtle interaction between pro- and anti-inflammatory processes determines its progression to inflammation resolution or to chronic inflammation. In this study, we propose a generic model of inflammation through a system of reaction-diffusion equations involving various inflammatory and anti-inflammatory cells and cytokines. We investigate the formation of patterns, determined by the emergence of Turing structures, through linear stability analysis and numerical simulations. These theoretical findings are further supported by observations of similar patterns in skin diseases.

Skin inflammation associated with chronic diseases has the direct action of keratinocytes in its immunopathogenesis, leading to a series of immune responses. However, there are still no highly targeted treatments, and the development of more specific therapies is highly desirable. In the present work, nanocapsules containing quinizarin (QZ/NC) were developed, evaluating their act in a model of the keratinocytes inflammatory process in vitro with the action of Photodynamic Therapy, analyzing the permeation in a 3D skin model. Physicochemical, stability, cytotoxicity and permeation analyses of the nanomaterials were carried out. The nanocapsules showed desirable physicochemical characteristics and were stable during the analysis period, without spectroscopic modifications. The cell viability test carried out showed no cytotoxicity at the lowest QZ/NC concentrations. The permeation and cellular uptake studies showed the permeation of QZ/NC in 3D skin models and the intracellular incorporation and internalization of the drug, enhancing its action in the drug delivery technique. Promising results were presented using the model developed to induce the inflammatory process in vitro and applying the synthesized nanomaterial in conjunction with PDT, where a decrease in the levels of cytokines analyzed was observed, representing a possible new therapeutic approach for inflammatory skin diseases.

The potential advantages of plant-based interventions in decreasing the incidence and lessening the morbidity and mortality of COVID-19 are yet to be widely acknowledged. Nevertheless, recent publications propose that these interventions could be effective. Our cardiology center conducted an interventional study in which we incorporated plant-based foods and provided supplementation to 3470 elderly COVID-19 patients with multiple comorbidities. We pay close attention to the precise selection of food items, the application of appropriate processing methods, and the provision of nourishing meals to our patients. Our outcome was highly successful as we achieved a zero mortality rate, and none of our patients experienced worsening conditions or required hospitalization. In this review article we present the mechanisms how plant-based and supplement interventions can mitigate COVID-19 disease severity and mortality. And experts have validated our hypotheses very recently. The measures and methods used to address the ongoing SARS-CoV-2 pandemic through plant-based interventions and supplements are effective and may help prevent or manage future pandemics.

Abstract: This study aims to evaluate the effectiveness of plant-based diets and supplement interventions in mitigating the severity and mortality of COVID-19 patients. Observational research suggests that a diet high in plant-based foods may decrease the likelihood and severity of SARS-CoV-2 infection. However, several studies have faced criticism regarding the accuracy of obtaining dietary questionnaires and the insufficient intake of essential vitamins and minerals in such diets. To address these issues, this study employed a prospective interventional design that strictly controlled the quality, quantity, and processing of plant-based foods provided. Furthermore, the study incorporated supplementation, which enhanced the anti-viral, anti-inflammatory, antioxidant, antithrombotic, and immunomodulatory properties of a plant-based diet against the SARS-CoV-2 virus. Of the 3,470 COVID-19 elderly patients, half already followed a plant-based diet, and the other half new patients, both with various comorbidities, were intervened with a plant-based diet and supplementation. The results showed that the participants in the non-plant-based diet group were twice as likely to have experienced moderate disease (with 95% confidence limit: 1.42-3.12) and 2.4 times more likely to have experienced severe disease (with 95% confidence limit: 1.2-5.0) with a significant p-value of less than 0.0005 and 0.016 respectively, compared to those in the PBD group. During the interventions, none of the participants experienced disease progression or hospitalization, and there were no reported deaths by the end of the study. The outcome was highly favorable and aligned with the researchers' expectations, as COVID-19 morbidity and mortality rates in Indonesia were among the highest in Asia. This research may provide significant insights into the prevention and management of COVID-19 and aid in better preparation for future pandemics.

Background: Platelets are increasingly recognised for their multifaceted roles in inflammation beyond their traditional involvement in haemostasis. This review consolidates knowledge on platelets as critical players in inflammatory responses. Methods: This study did an extensive search of electronic databases and identified studies on platelets in inflammation, focusing on molecular mechanisms, cell interactions, and clinical implications, emphasising recent publications. Results: Platelets contribute to inflammation via surface receptors, release of mediators, and participation in neutrophil extracellular trap formation. They are implicated in diseases like atherosclerosis, rheumatoid arthritis, and sepsis, highlighting their interaction with immune cells as pivotal in the onset and resolution of inflammation. Conclusion: Platelets are central to regulating inflammation, offering new therapeutic targets for inflammatory diseases. Future research should explore specific molecular pathways of platelets in inflammation for therapeutic intervention.

Background The distinctive feature of liver fibrosis is the progressive replacement of healthy hepatic cells by extracellular matrix protein, which is abundant in collagen I and III with impaired matrix remodelling. The activation of myofibroblastic cells enhances a fibrogenic response of complex interactions of hepatic stellate cells, fibroblasts and inflammatory cells to produce excessive deposition of extracellular protein matrix. This process is activated by multiple fibrogenic mediators and cytokines such as TNF-α and IL-1ß with decrease in the anti-fibrogenic factor NF-ҡß. Mesenchymal stem cells (MSCs) represent a promising therapy for liver fibrosis giving more advanced regenerative influence when cultured with extrinsic or intrinsic proliferative factors, cytokines, anti-oxidants, growth factors, and hormones such as Melatonin (MT). However, previous studies showed conflicted findings concerning the therapeutic effects of adipose (AD) and bone marrow (BM)-MSCs, therefore, the present work aimed to accomplish a comparative and comprehensive study investigating the impact of MT pre-treatment on the immunomodulatory, anti-inflammatory and anti-apoptotic effects of AD and BM-MSCs and to critically analyse whether MT pre-treated both AD-MSCs and BM-MSCs reveal equal or different therapeutic and regenerative potentials in CCl4-injured liver of experimental rat models. Materials and methods Six groups of experimental rats were used with ten rats in each group; group I (control group), group II (CCl4-treated group), group III (CCl4 and BM-MSCs treated group), group IV (CCl4 and MT pre-treated BM-MSCs group), group V (CCl4 and AD-MSCs treated group) and group VI (CCl4 and MT pre-treated AD-MSCs group). Liver function tests, gene expression of inflammatory, fibrogenic, apoptotic and proliferative factors were analysed. Histological and immunohistochemical changes were assessed. Results The present study compared the capability of AD and BM-MSCs, with and without the pre-treatment of MT, to reduce hepatic fibrosis. Both types of MSCs improved hepatocyte function by reducing the serum levels of (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and total bilirubin (TBIL). In addition, the changes in the hepatocellular architecture including the hepatocytes, liver sinusoids, central veins, portal veins, biliary ducts and hepatic arteries showed decrease hepatocyte injury and cholestasis with reduction of inflammation, apoptosis and necrosis of the hepatic cells together with inhibition of liver tissue fibrosis. These results were augmented by the analysis of the expression of the anti-inflammatory cytokines TNFα and IL-1β, the anti-fibrogenic factor NF-ҡß, the apoptotic factor caspase-3 and the proliferative indicators antigen Ki-67 and proliferating cell nuclear antigen (PCNA). These findings were found statistically significant, with the best results in the rats received AD-MSCs pre-treated with MT, denoting better regenerative and therapeutic effects. Conclusion AD-MSCs, pre-treated with MT, are superior to BM-MSCs due to their better efficacy in improving hepatic fibrosis and promoting the therapeutic and regenerative capability of liver tissue. They represent a very significant tool for future stem cell use in tissue regeneration strategy for the treatment of liver diseases.

Previous studies have revealed the microbial metabolism of dietary choline in the gut, leading to its conversion into trimethylamine (TMA), a precursor of the cardiovascular inflammatory marker trimethylamine N-oxide (TMAO). Polymethoxyflavones (PMFs), exemplified by tangeretin, demonstrate efficacy in mitigating TMAO-induced cardiovascular inflammation. However, the specific mechanism by which these compounds exert their effects, particularly in modulating the gut microbiota, remains uncertain. This investigation focused on tangeretin, a representative PMFs, exploring its influence on the gut microbiota and the choline-TMA conversion process. Experimental results showed that tangeretin treatment attenuated the population of CutC-active bacteria, specifically Clostridiaceae and Lactobacillus, induced by choline chloride in rat models. This inhibition resulted in reduced efficiency in choline conversion to TMA, thereby ameliorating cardiovascular inflammation resulting from prolonged choline consumption. In conclusion, tangeretin's preventive action against cardiovascular inflammation is intricately linked to its targeted modulation of TMA-producing bacterial activity.

Background: A decline in the prevalence of Helicobacter pylori infection has been claimed to increase the probability of developing atopic diseases. Aims: To evaluate the prevalence of atopic disorders in a pediatric population according to seropositivity against H. pylori. Methods: Children referred to the local Pediatric Hospital were investigated to identify risk factors, especially H. pylori infection, associated with atopic disorders. A questionnaire, including demographics, house size, history of breastfeeding, residence, school or daycare center attendance, exposure to animals, and a diagnosis of atopy, was filled out by a trained pediatrician according to parents’ answers. A blood sample was collected from each participant. Results: Seroprevalence of H. pylori infection was 11.7% among 492 children (240 females); 32 of them had a diagnosis of asthma and 12 of allergy. No one child showed both conditions. Statistically significant differences in H. pylori seropositivity were not detected between children with or without atopy (8.4 vs. 12.6; p=0.233). Although atopic disorders were more frequent in children exposed to traditional risk factors none showed to be significant after adjusting for all covariates. Conclusions: H. pylori infection, serologically assessed, was not significantly associated with a reduced risk of atopic diseases in children.

Immune disorders, characterized by dysregulation at cellular and inflammatory levels, result from a complex interplay of genetics and environmental factors that lead to an abnormal immune response against autoantigens, triggering tissue damage. Recent research highlights reactive antibodies as key players in autoimmune diseases and graft rejection, but the complexity of their determination limits their use in clinic. Hence, we studied the specific binding profile of serological antibodies against a panel of cellular membranes in order to determine whether this antigenic panel could be used to diagnose specific immune disorders in humans. For this purpose, cell membrane microarrays of spleen, liver, and kidney tissues of monkey, rat, and human were developed, and human sera were analyzed, including healthy controls, patients with autoimmune disorders, and kidney transplant patients. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and Human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in the serum of patients as potential biomarkers of immune disorders.

N-palmitoylethanolamine (PEA) is an endocannabinoid-like compound first encountered within lipid fractions of specific foods and has intrigued researchers since the 1950s due to its therapeutic effects. This study aims to explore the therapeutic promise held by PEA as an anti-inflammatory and immunomodulatory agent. Therapeutic impact of PEA reverberates across diverse physiological systems, as the central nervous system, gastrointestinal tract, vascular network, digestive and respiratory system. Additionally, it was effective in pain management, reduction of inflammation and immune responses. These attributes have fostered collaborations targeting conditions such as Alzheimer's disease, multiple sclerosis, cerebral ischemia, neuroinflammation, general inflammation, pain, coagulopathy, steatohepatitis, and acute lung injury. PEA operates both independently and in synergy with other compounds, like paracetamol, luteolin, and oxymetazoline. This efficacy stems from its interactions with pivotal targets including PPARα, PPAR-δ, PPAR-γ, CB1, CB2, GPR55, and TRPV1. Additionally, PEA exerts a direct influence on the inflammatory cascade, orchestrating precise adjustments in immune responses. Numerous animal studies have elucidated the inherent potential of PEA. Nevertheless, the imperative of reinforcing clinical investigation is evident. This review notably underscores the pivotal necessity for methodologically rigorous clinical trials to definitively establish the translational efficacy of PEA in ameliorating diverse inflammatory pathologies within the human milieu.

The escalating prevalence of particulate matter (PM) has raised serious concerns regarding its detrimental effects on human health. This study aimed to investigate the potential of fermented blueberry and black rice (FBBR) in mitigating the effects of PM2.5, both in SH-SY5Y cells and mice exposed to PM2.5. Various assays, including MTT, NO, western blot, ELISA, and behavioral studies (MWM and Y-maze) were conducted. Our results demonstrated that PM2.5 induced significant cytotoxicity and elevated nitric oxide (NO) production at a concentration of 100μg/mL of PM2.5 in SH-SY5Y cells. Additionally, administration of FBBR effectively attenuated PM2.5-induced cytotoxicity and suppressed NO production in SH-SY5Y cells. In an intranasal instilled mice model, exposure to 10 mg/kg body weight of PM2.5 resulted in cognitive impairments. However, FBBR treatment ameliorated these impairments in both the Y-maze and MWM tests in PM2.5-exposed mice. Furthermore, FBBR administration increased the expression of brain-derived neurotrophic factor (BDNF) and reduced inflammatory markers in the brains of PM2.5-exposed SH-SY5Y cells. These findings underscore the detrimental effects of PM2.5 on the nervous system and highlight the potential of FBBR as a nutraceutical agent for mitigating these effects. Overall, this study emphasizes the urgency of addressing the harmful impact of PM2.5 on the nervous system and suggests the promising role of FBBR as a protective intervention against the adverse effects associated with PM2.5 exposure.

SARS-CoV-2 infection triggers distinct patterns of disease development, characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SL) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n=55), COVID-19 patients (n=204), and convalescent individuals (n=77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, the predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) d18:1/24:1 and d18:1/24:0 was associated with increased risk. Moreover, we observed enhanced expression of key enzymes involved in SL pathway, in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

Inflammation is the response of the immune system to infection and injury, with complex interactions with the body, tissues and cells, and plays an important role in the initiation and progression of many diseases such as cancer and cardiovascular disease. Traditional excipients functioning as drug delivery systems can reduce the side effects of systemic distribution of inflammatory drugs. Oil phase, a common excipient in nanoemulsions (NEs), has the advantages of assisting the formation of emulsions, loading lipophilic drugs, thermodynamic stability, wide sources, low price and easy availability. In particular, some of them, like linolenic acid and medium chain triglyceride (MCT), also function as inhibitors of systemic inflammation marker and vascular inflammation marker. However, the influences of different oil phases on the construction of NEs and their distribution in vivo have not been fully investigated. Herein, Tween 80 and ethyl alcohol were screened out as emulsifiers and co-emulsifiers, and three different oil phases used in clinical practice widely, including MCT, oleic acid (OA), and ethyl oleate (EO), were selected as the oil phase to prepare NEs delivery platform. Three NEs had consistent size, potential, morphology, excellent stability and mitochondrial localization function. Importantly, they exhibited superior cellular uptake capacity in inflammatory-injuried human umbilical vein endothelial cells and significantly targeted the brain, lung, heart and thoracic aorta in the lipopolysaccharide-induced mouse and zebrafish larvae inflammation models. Meanwhile, the fluorescence intensities of three NEs were different in these organs, suggesting that their differential enrichment might provide alternative delivery platform for disease treatment in the corresponding organs.

Extensive evidence indicates that activation of P2X7 receptor (P2X7R), an ATP-gated ion channel highly expressed in immune and brain cells, is strictly associated with the release of extracellular vesicles. Through this process, P2X7R-expressing cells regulate non-classical protein secretion and transfer bioactive components to other cells, including misfolded proteins, participating in inflammatory and neurodegenerative diseases. In this review, we summarize and discuss the studies addressing the impact of P2X7R activation on extracellular vesicle release and their activities.

Osteoarthritis (OA) is a debilitating degenerative joint disease that results in chronic pain and inflammation due to progressive mechanical and proteolytic cartilage degradation. Articular chondrocytes, the main cell type present in cartilage, are responsible for the deposition and maintenance of the cartilage extracellular matrix (ECM). However, following damage and inflammation, chondrocytes undergo hypertrophy, apoptosis, and contribute to inflammation and ECM degradation. NF-κB signaling is known to be dysregulated in OA. TRAPPC9, a vesicle trafficking protein, is known to directly activate NF-κB signaling in neuronal and bone cells, however, the biological significance of this protein in chondrocytes has yet to be elucidated. Here, we demonstrate that TRAPPC9 enhances pro-inflammatory gene and protein expression in murine primary articular chondrocytes. Furthermore, we show that TRAPPC9 elicits these responses via phosphorylation of P-100 that activates non-canonical NF-κB signaling. Taken together, these findings suggest TRAPPC9 may be a potential therapeutic target to decrease inflammation and matrix degradation during OA pathology.

People with HIV (PWH) experience higher rates of cardiovascular events (CVEs) compared with the general population. A substantial body of evidence supports that select biomarkers of inflammation (soluble CD14 [sCD14], soluble CD163 [sCD163], highly sensitive C-reactive protein [hs-CRP], interleukin-6 [IL-6]), and coagulation (D-dimer) are elevated in PWH and related to increased rates of CVEs. Our previous work showed that smoking compared with nonsmoking was associated with significantly elevated sCD14, a biomarker of monocyte activation. We aimed to explore the effect of electronic cigarette (EC) provision on inflammatory biomarkers in PWH who smoked daily and then switched to an EC. Nineteen PWH were enrolled in a pilot study in which an EC and e-liquid were provided weekly or 8 weeks. Blood specimens for inflammatory biomarker analysis were obtained at baseline (BL) and at week 8. Biomarker levels were high at BL and did not differ significantly at week 8. There were small nonsignificant reductions in sCD163 and CRP levels. Non-significant increases in IL-6, D-dimer and sCD14 levels were also noted. Use of ECs for 8 weeks does not appear to significantly increase or decrease inflammatory biomarker levels in SWH. Further research with larger samples and a control group is needed.

ABSTRACT: Understanding the basis of osteoarthritis (OA) has seen some interesting advancements in recent years. It has been observed that cartilage degeneration is preceded by subchondral bone lesions, suggesting a key role of this mechanism within the pathogenesis and progression of OA, including the formation of ectopic bone and osteophytes. Moreover, low-grade, chronic inflammation of the synovial lining has gained a central role in the definition of OA pathophysiology, and central immunological mechanisms, innate but also adaptive, are now considered crucial in driving inflammation and tissue destruction. In addition, the role of neuroinflammation and central sensitization mechanisms has been characterized as underlying causes of pain chronicity. This has led to a renewed definition of OA, which is now intended as a complex multifactorial joint pathology caused by inflammatory and metabolic factors underlying joint damage. Since this evidence can directly affect the definition of the correct therapeutic approach to OA, an improved understanding of these pathophysiological mechanisms is fundamental. This review provides an overview of the most updated evidence on OA pathogenesis; it presents the most recent insight on the pathophysiology of OA, describing the interplay between immunological and biochemical mechanisms proposed to drive inflammation and tissue destruction, as well as central sensitization mechanisms. Moreover, although the therapeutic implications consequent to the renewed definition of OA are beyond this review scope, some suggestions for intervention have been addressed.

Purinergic signaling is that nucleotides (especially ATP) and adenosine are utilized as transmitter molecules, which play an important role in the immune system. In the extracellular ventricle, ATP plays a significant role of pro-inflammatory molecules mainly through activating P2 receptors, while adenosine plays the role as anti-inflammatory molecule mainly through activating P1 receptors. As we know，neutrophils are the most abundant immune cells in our circulation and have become an essential part of coordinating a series of complex events during inflammatory diseases. However, due to the destruction of inflammatory substances from neutrophils, the activation of neutrophils is fine-tuned, and purinergic signaling is associated with this process. As a matter of fact, altering the balance between P2 and P1 signals is of great importance for neutrophils to exert immune activities properly. Here, we review the role of purinergic signaling in regulatory function of neutrophils during inflammatory disease, and then discuss the potential contribution of targeted purinergic signals in the treatment of the neutrophil during inflammatory diseases.

Background: HIV is accompanied by production of proinflammatory cytokines which are regarded as critical in neuronal damage, leading to brain dysfunction, hence the need to identify cytokine biomarkers sensitive to brain damage. Methods: We applied MRI volumetric neuroimaging and high throughput Luminex based immunoassays to examine the relationship between cortical white matter, subcortical gray matter and total gray matter brain volumes and plasma cytokines in HIV indviduals using generalised linear models and Partial least square regression model. Results: Higher plasma inflammatory cytokines CCL5/RANTES and MCP-1 were significantly associated with lower cortical white matter volume. Higher IL-6 was associated with both lower subcortical gray matter and lower total gray matter, whereas higher IL-8 and GM-CSF were associated with lower total gray matter only. Higher VEGF, PDGF-BB and IL-9 were associated with higher cortical white matter volumes. After standardisation and adjusting for clinical and demographic variables, IL-6, IL-8, MCP-1 remained associated with lower volumes of the three brain regions whereas IL-9, VEGF and PDGF-BB were associated with higher volumes. Conclusions: Association proinflammatory cytokines RANTES, MCP-1 and IL-6 with lower brain volumes could imply possible involvement in neurodegerative processes in HIV infection while IL-9, VEGF and PDGF may have a neuroprotective or neurotrophic role.

Metformin（Met） is a commonly used drug in the treatment of type 2 diabetes. Currently, it has been found that Met can effectively reduce the incidence of stroke and exert anti-inflammatory effects. However, its role in ischemia-reperfusion (I/R) induced nerve injury remains unclear. This study aims to investigate the neuroprotective effects of Met in I/R-induced neuron injury as well as the underlying mechanism.A middle cerebral artery occlusion (MCAO) model was established in SD rats, which were then treated with different doses of Met.Neurological deficits of rats were measured at different times post-surgery. TTC staining to observe the volume of cerebral infarction.HE staining was performed to observe pathological changes of brain tissues .Immunohistochemistry was performed to observe the expression of inflammatory factors in the cerebral tissues .qRT-PCR method was used to detect the relative expression of PI3K、Akt mRNA in cells after 24 h of drug action.Western blot method was used to detect the expression of PI3K、p-PI3K、Akt and p-Akt in hippocampus.What’s more, in vitro experiments were performed on BV2 microglia to verify the role of Met against oxygen-glucose deprivation (OGD). As a result, Met dose-dependently attenuated neurological deficits and neuronal apoptosis. Besides, Met administration also significantly reduced BV2 cells apoptosis and inflammatory response. Mechanistically, Met inactivated PI3K/Akt pathway induced by I/R and OGD, while upregulated PI3K. In conclusion, Met protected rats from cerebral I/R injury via reducing neuronal apoptosis and microglial inflammation through PI3K/Akt pathway.

Background: obese pre-diabetics have altered expression of cytokines, and sirtuin-1, that might influence myocardial function via microRNAs (miRs) expression. Objectives: to evaluate inflammatory/oxidative stress, miRs’ expression and cardiovascular function in obese pre-diabetics randomly assigned to metformin therapy vs. placebo vs. normo-glycemics at 12 months of follow-up. Materials and methods: eighty-three obese patients enrolled for abdominoplastic surgery, were divided in pre-diabetics (n 55), normo-glycemics (n 28), and assigned to hypocaloric diet. Pre-diabetics were randomly assigned to metformin (n 23) or to placebo (n 22) plus hypocaloric diet. Results: at enrollment, pre-diabetics obese vs. normo-glycemic presented higher values of glucose, insulin resistance (HOMA-IR), inflammatory/oxidative stress markers, miR-195 and miR-27, and lower values of sirtuin-1 (p<0.05). At 12 months of follow up, obese pre-diabetics with metformin vs. placebo experienced significant reduction of glucose values, HOMA-IR, and inflammatory/oxidative stress markers, with significant reduction of intima-media thickness (IMT), septum and posterior wall thickness, and left ventricle mass (LVM), (p <0.05). At 12 months of follow-up, obese pre-diabetics with placebo vs. normo-glycemics had higher values of inflammatory/oxidative stress markers, higher values of IMT, septum and posterior wall thickness, LVM, and myocardial performance index (MPI), (p<0.05). Obese pre-diabetics in metformin vs. placebo, and obese pre-diabetics with placebo vs. normoglycemics, had significant differences about IMT, MPI, and LVM (p<0.05). Obese pre-diabetics in metformin vs. placebo showed significant reduction of serum miR-195 and miR-27 (p<0.05). Obese pre-diabetics in metformin vs. normoglycemics showed higher expression of serum miR-195 and miR-27 ( p<0.05). Finally, we found inverse relation between IMT and insulin (R -0.351), HOMA-IR (R -0.340), miR-195 (R -0.355), miR-27 (R -0.181); between LVEF and Insulin (R -0.332), HOMA-IR (R -0.142), miR-195 (R -0.297) and miR-27 (R -0.163). We found inverse correlation between LVM and sirtuin-1 (R -0.272), Insulin (R -0.810), HOMA-IR (R-0.183), miR-195 (R -0.446) and miR-27 (R-0.433), and direct correlation with interleukin-6 (R 0.195). MPI inversely linked to miR-195 (R -0.260) and miR-27 (R -0.591). Conclusion: in obese pre-diabetics metformin therapy significantly reduces inflammation/oxidative stress, circulating miR-195 and miR-27, causing reduction of LVM, IMT and amelioration of cardiac performance.

Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P<0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P<0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.

Acidic glycosphingolipids, gangliosides are highly and consistently expressed in nervous tissues of vertebrates at high levels. Therefore, they have been believed to be largely involved in the development and function of nervous systems. Recent studies with genetic engineering of glycosyltransferase genes have revealed novel aspects of roles of gangliosides in the regulation of nervous tissues with substantial basis. In this review, novel findings on the ganglioside functions and their modes of action elucidated mainly by studies of gene knockout mice have been summarized. In particular, roles of gangliosides in the regulation of lipid rafts to maintain the integrity of nervous systems have been reported with a focus on the roles in the regulation of neuro-inflammation and neurodegeneration via complement systems. In addition, recent advances in the studies of congenital neurodisorders due to the genetic mutaions of ganglioside synthase genes, and also in the techniques for the analysis of ganglioside functions have been introduced.

Background: Activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) play a key role in SCZ and treatment resistant SCZ. There are only few data on immune and endogenous opioid system (EOS) interactions in SCZ and treatment resistant SCZ.Aim of the study: We examined serum β-endorphin, endomorphin-2 (EM2), mu-opioid (MOR) and kappa-opioid (KOR) receptors, and interleukin (IL)-6 and IL-10 in 60 non responders to treatment (NRTT), 55 partial RTT (PRTT) and 43 normal controls.Results: Serum EM2, KOR, MOR, IL-6 and IL-10 were significantly increased in SCZ as compared with controls. β-endorphin, EM2, MOR and IL-6 were significantly higher in NRTT than in PRTT. There were significant correlations between IL-6, on the one hand, and β-endorphin, EM2, KOR, and MOR, on the other, while IL-10 was significantly correlated with MOR only. A large part of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation and formal thought disorders was explained by the combined effects of EM2 and MOR with or without IL-6 while increased KOR was significantly associated with all symptom dimensions. Increased MOR, KOR, EM2 and IL-6 were also associated with neurocognitive impairments including in episodic, semantic and working memory and executive functions.Conclusion: The EOS contributes to SCZ symptomatology, neurocognitive impairments and a non-response to treatment. In SCZ, EOS peptides/receptors may exert CIRS functions, whereas increased KOR levels may contribute to the pathophysiology of SCZ and EM2 and KOR to a non-response to treatment.

Sutherlandia frutescens (S. frutescens) has been traditionally used as an herbal medicine to ameliorate symptoms associated with cancer, infectious diseases, as well as inflammation. The objective of this investigation was to explore the impact of S. frutescens on the expression of genes in a murine macrophage cell line (i.e., RAW 264.7). We found that treatment with an ethanolic-extract of S. frutescens (SFE) 1 h prior to the stimulation with LPS and IFNγ for 24 h significantly affected the expression of 715 genes in RAW 264.7 cells. When the post-stimulation period was shortened to 8 h, the number of genes that were significantly impacted by SFE diminished to 50. Pathway analysis revealed that inflammatory signaling pathways, such as NF-κB, MAPK, and TNF, as well as signaling pathways associated with immune-related responses, were inhibited by SFE treatment. These findings are consistent with previously reported anti-inflammatory activity of SFE and enable better understanding of the immune-modulating properties of this botanical. To our knowledge, this represents the first report on the impact of S. frutescens on global gene expression in an immune cell population.

Obesity and chronic low-grade inflammation are becoming global epidemics. The dysbiosis has a specific role in the metabolism and energy stocks of the host. The discovery that a low-grade of inflammation could be directly connected to the intestinal microbiota metabolic endotoxemia (elevated levels of plasma lipopolysaccharides) has allowed the identification of novel mechanisms involved in the control of the intestinal barrier. In this review, it will analyze the latest news to explain how human symbiotic microorganisms participate in the growth of the fat reserves and promote insulin resistance as a low-grade inflammation. Besides, it will discuss new treatments with probiotics and prebiotics as a promising therapeutic approach to reverse the host's metabolic changes linked to dysbiosis observed in obesity.

The iridoids of H. diffusa play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism is lack of study. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Its anti-inflammatory mechanism was confirmed by in intro experiment and molecular docking analysis. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.

Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. These results indicate that NGF/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioural data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.

Background: The role played by the non-dominant parietal lobe in motor cognition, attention and spatial awareness networks has potentiated the use of awake surgery. When this is not feasible, asleep monitoring and mapping techniques should be used to achieve an onco-functional balance. Objective: This study aims to assess the feasibility of a dual-strip method to obtain direct cortical stimulation for continuous real-time cortical monitoring and subcortical mapping of motor and visual pathways simultaneously in parietal lobe tumour surgery. Methods: Single-centre prospective study between May’19-November’20 of patients with intrinsic non-dominant parietal-lobe tumours. Two subdural strips were used to simultaneously map and monitor motor and visual pathways. Results: Fifteen patients were included. With regards to motor function, a large proportion of patients had abnormal interhemispheric resting motor threshold ratio (iRMTr) (71.4%), abnormal Cortical Excitability Score (CES) (85.7%), close distance to the corticospinal tract – Lesion-To-Tract Distance (LTD) – 4.2mm, Cavity-To-Tract Distance (CTD) – 7mm and intraoperative subcortical distance - 6.4mm. Concerning visual function, the LTD and CTD for optic radiations (OR) were 0.5mm and 3.4mm, respectively; the mean intensity for positive subcortical stimulation of OR was 12mA±2.3mA and 5/6 patients with deterioration of VEPs>50% had persistent hemianopia and transgression of ORs. 12 patients remained stable, one patient had a de-novo transitory hemiparesis, and two showed improvements in motor symptoms. A higher iRMTr for lower limbs was related with a worse motor outcome (p=0.013) and a longer CTD to OR was directly related with a better visual outcome (p=0.041). At 2 weeks after hospital discharge, all patients were ambulatory at home and all proceeded to have oncological treatment. Conclusion: We propose motor and visual function boundaries for asleep surgery of intrinsic non-dominant parietal tumours. Pre-operative abnormal cortical excitability of the motor cortex, deterioration of the VEP recordings and CTD<2mm from the OR were related to poorer outcomes.

Development of effective treatments for high-grade glioma (HGG) is hampered by 1) the blood-brain barrier (BBB), 2) an infiltrative growth pattern, 3) rapid development of therapeutic resistance, and, in many cases, 4) dose-limiting toxicity due to systemic exposure. Convec-tion-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and in-crease therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

Post-concussion syndrome, recently recognized as a complication of mild traumatic brain injury, is considered a consequence of the summative effect of multiple concussions received over lifetime. In elderlies, the main mild brain trauma mechanism is fall (low impact force). Many falls are often not reported or noticed but may generate serious medical and medico-legal consequences. Our research question was to find if a single, very mild brain trauma can induce neuro-behavioral consequences in elderlies. One database was queried (PubMed – MeSH terminology) looking for histopathological, neuro-cognitive and behavioral changes that can be generated by sub-concussional trauma in senescent rodents, in comparison with young animals. 41 published research articles were selected. 17 of them used very mild brain trauma in young and senescent animals, in the same experiment (6 rats and 11 mice). 24 articles evaluated the effect of sub-threshold brain trauma in adult animals (no control group). Five trauma models were used (blast models were excluded). Neuro-inflammatory changes were detected immediate after very mild primary impact. In young animals, observed pathology disappeared fast (after 3 to 7 days). Increased apoptosis, mild axonal injury in white matter tracts plus maladaptive astrogliosis and microglial activation was stronger in aged animals, persisted over time (8 months) and significantly altered animals’ cognition and behavior. Associated preexisting pathology (hypertension, tau protein deposits, microbleeds, reactive inflammation) was often responsible for amplification of the primary impact results. As translation of observation is the weak spot of pathology and behavior animal research, further investigation is needed before to conclude that even a single, very mild brain trauma may have medical consequences on human senescent brain.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

Obesity is among the most prevalent risk factors in the severe forms of Coronavirus disease 2019 (COVID-19) infection. COVID-19 patients with obesity often face severe complications that might be associated with overexpression of adiponectin, inflammatory cytokines, and angi-otensin-converting enzyme 2 (ACE2) receptors in visceral fat. The pre-existing subclinical in-flammation associated with obesity can also lead to severe inflammatory responses. Elevation of pro-inflammatory cytokines considerably activates coagulation cascades, including the tissue factor (TF) pathway. The hypercoagulable state in COVID-19 is presented by severe pulmonary complications such as venous thromboembolism (VTE), disseminated intravascular coagulation (DIC), and disruption of vascular endothelial cells which can lead to severe complications and death. The interaction between inflammatory response and coagulation mechanism in COVID-19 patients with obesity warrants a further understanding of prognosis and potential therapeutic approaches. This review discussed the crosstalk between inflammation and coagulopathy in obesity-related severe COVID-19 infection.

Background: Previous studies of the hydroethanolic extract of Virola elongata inner stem bark (HEVe) have demonstrated its antioxidant, gastroprotective, and antiulcer properties, but have not evaluate its anti-inflammatory potential. Methods: HEVe was obtained by maceration and phytochemicallly analyzed. Its systemic anti-inflammatory activity was assessed by its effect on lipopolysaccharide (LPS)-induced peritonitis in mice. HEVe gel (HEgVe) was employed to evaluate topical anti-inflammatory activity by measuring the ear edema resulted from croton oil-induced dermatitis in mice. Cell viability assay was conducted to determine non-cytotoxic concentrations of HEVe. RAW 264.7 cells were stimulated by LPS to determinate cytokine and nitric oxide production.Results: Phytochemical analysis of HEVe revealed the presence of phenolic acids, neolignans, flavonoids, and monomeric catechins. Oral treatment of acute peritonitis with HEVe reduced total leukocytes, neutrophils, TNF-α and IL-1β, and elevated IL-10 levels. The application of HEgVe reduced local edema. The HEVe on RAW 264.7 cells exhibited no cytotoxicity and cells with HEVe reduced TNF-α, IL-1β, and NO levels, and increased IL-13 levels. Conclusions: HEVe demonstrated systemic and topical multitarget anti-inflammatory activity, which is likely due to the combined effects of secondary metabolites. HEVe emerges as a promising herbal remedy for inflammation with minimal cytotoxicity, emphasizing its potential therapeutic significance.

Senolytic and senomorphic therapies gain more and more attention in the last decade. This kind of therapy is based on the killing of cellular senescent cells without harming the “normal” cells. Ageing is not a disease. Clinical studies on healthy people will be difficult to conduct. Therefore, one possibility is to draw on the large repertoire of medicinal plants and use their sneolytic properties to provide mild, anti-ageing therapies. Chamomile, goldenrod, reishi and green tea were tested for their ability to trigger senolysis quercetin was used as control substance. Cellular senescence was induced with 25µM etoposide in human dermal fibroblasts and established for at least 14 days. The plant extracts were tested for their antioxidant potential (DPPH assay) and their polyphenol content. Senolysis was determined by presto blue assay of young and etoposide-induced senescent cells, and ß-Gal assays were also performed. The senomporphic properties of the plants were investigated using IL-6 ELISA and qPCR. It turned out that chamomile triggers a kind of cytokine storm and causes the cytokine values in the Elisa and in the qPCR to rise extremely, and other senescence-associated phenotype (SASP) markers were also elevated. Goldenrod and quercetin tend to have a senolytic and senomorphic effect respectively. Regarding the senolytic and senomorphic properties of herbs, we have found that all tested herbs can have a senolytic effect, and a senomorphic effect of quercetin has also been uncovered. With regard to the effect of chamomile, however, we can say that seemingly harmless tea products may have harmful effects, especially in combination with chemotherapy, at least in cell culture experiments.

Asthma is a chronic inflammatory disease for which the main anti-inflammatory drugs for better disease control are steroids or corticosteroids. The use of steroids in asthma patients, in particular in uncontrolled asthma patients, is associated with an increased risk of osteoporosis and fragility fractures. A single oral corticosteroids course increases the risk of osteoporosis and continual use of inhaled corticosteroids is correlated over time to an increased risk for both bone conditions. With the use of new, available biologic therapies for asthma, perhaps even anticipating the times of their use in what are the steps of therapeutic management, in the current guidelines and with targeted strategies of prevention it may be possible to improve asthma management, preventing some comorbidities, such as osteoporosis.

Similar to humans, the renin-angiotensin-aldosterone system (RAAS) plays a key role in regulating blood pressure and body fluid homeostasis in dogs and cats. The classical RAAS pathway, which involves the conversion of angiotensin I to angiotensin II by the angiotensin converting enzyme (ACE), leads to aldosterone production and associated maladaptive effects in cardiovascular and renal diseases. Recent studies have highlighted the alternative RAAS pathway, which counteracts these effects through angiotensin 1-7, promoting vasodilation and reducing inflammation. Beyond RAAS modulation, RAAS inhibitors have been shown to exert significant anti-inflammatory properties. This is particularly relevant given the American Heart Association's recent focus on Cardiovascular-Kidney-Metabolic (CKM) health, which emphasizes the interconnected risks of cardiovascular disease, chronic kidney disease (CKD), type 2 diabetes, and obesity. These conditions share common pathophysiological pathways, including chronic inflammation, oxidative stress, and metabolic dysregulation. Advances in biomedical research, including the development of adult stem cell-derived canine organoids, provide impetus to study the effects of RAAS modulators and new CVD drugs on CKM health, with a focus on epithelial inflammation within the context of One Health.

the close phylogenetic relationship between ascidians (Tunicata) and vertebrates makes them a powerful model for studying the innate immune system. To better understand the nature and dynamics of immune responses and the mechanisms through which bacterial infections are detected and translated into inflammation in Ciona robusta, we applied an approach combining in vivo lipopolysaccharide (LPS) stimulation, immune-labelling and functional enzymatic analyses. The immunohistochemistry showed that toll-like receptor 4 (TLR4) and nuclear factor kappa B (NFκB) were expressed during the inflammatory pharynx response 4 hours post-LPS, with formation of immune-stained haemocyte nodules in the vessel lumen. Pharynx vessel endothelium also took part in the inflammatory response. Observations of histological sections from naive and MS-inoculated ascidians confirmed immuno-positive tissue response. Enzyme immune parameters – which included the activity of phenoloxidase, glutathione peroxidase, lysozyme, alkaline phosphatase and esterase – showed up-modulation 4 hours after LPS injection, confirming their involvement during ascidian inflammatory response. These findings provide new insights into the mechanisms involved in LPS-induced C. robusta response and suggest that a broad innate immune mechanism is involved in the regulation of tunicate inflammatory responses.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Macrophages as a source and target of GDF-15

Receptor-interacting protein kinase 1 (RIPK1) plays a crucial role in controlling inflammation and cell death. Its function is tightly controlled through post-translational modifications, enabling its dynamic switch between promoting cell survival and triggering cell death. Phosphorylation of RIPK1 at various sites serves as a critical mechanism for regulating its activity, exerting either activating or inhibitory effects. Perturbations in RIPK1 phosphorylation status have profound implications for the development of severe inflammatory diseases in humans. This review explores the intricate regulation of RIPK1 phosphorylation and dephosphorylation and highlights the potential of targeting RIPK1 phosphorylation as a promising therapeutic strategy for mitigating human diseases.

Microglial cells are brain macrophages that support and protect the central nervous system enviroment. Aging induces alterations in microglial polarization, resulting in a shift towards a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding the involvement of microglia in neurodegenerative diseases like Alzheimer's and Parkinson's, is a critical topic to studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including downregulation of oxidative phosphorylation are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies.

Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies. Traditional pharmacological treatments aimed at slowing degeneration are ineffective in the long-term. Orthobiologics, regenerative agents derived from the patient’s own tissue, are a promising emerging therapy for degenerative disc disease. This review first outlines the pathophysiology of degenerative disc disease, highlighting the limitations of existing treatments and explores the orthobiologic tools for treating degenerative disc disease (platelet-rich plasma, mesenchymal stem cells). Their history in regenerative medicine is outlined, demonstrating how in vitro evidence informed preclinical animal studies on their efficacy in treating degenerative disc disease. Finally, clinical trials utilizing these treatment options are reviewed and directions for future research are outlined. Although the current clinical evidence available is limited to propagate their routine clinical usage the field holds immense potential in the management of DDD. There is room for these treatments to be optimized for effective consistent clinical outcomes in DDD.

The study evaluated the regenerative responses of the lacrimal functional unit (LFU) after Lacrimal Gland (LG) ablation. The LG of Wistar rats were submitted to G1) partial LG ablation, G2) partial ablation and transplantation of an allogeneic LG, or G3) total LG ablation, (n=7-10/group). The eye wipe test, slit-lamp image, tear flow, and histology were evaluated. RT-PCR analyzed inflammatory and proliferation mediators. The findings were compared to naïve controls after 1 and 2 months (M1 and M2). G3 presented increased corneal sensitivity, and the 03 groups have shown corneal neovascularization. Histology revealed changes in LG, and corneal inflammation. In the LG, there was an increase in MMP-9 mRNA of G1 and G2 at M1 and M2 and RUNX-1 at M1 and M2 in G1 and RUNX-3 mRNA at M1 in G1, and in G2 at M2. TNF-α mRNA rose in the corneas of G1 and G2 at M2. There was an increase in the IL-1β mRNA in the Trigeminal Ganglion of G1 at M1. Without changes in tear flow or evidence of LG regeneration, LG ablation or grafting are unreliable models for dry eye or LG repair in rats. The surgical manipulation extended inflammation to the LFU.

Background: The modified Duke index derived from coronary computed tomography angiography (CCTA) was designed to predict cardiovascular outcomes based on the severity of coronary ste-nosis. However, it does not take into consideration the presence or severity of peri-coronary in-flammation. The peri-coronary fat attenuation index (FAI) is a novel imaging marker determined by CCTA which reflects the degree of inflammation in the coronary tree in patients with coronary artery disease. Purpose: To assess the association between the modified Duke index assessed by CCTA, cardiovascular risk factors and peri-coronary inflammation in the coronary arteries of pa-tients with coronary artery disease. Methods: One hundred seventy-two patients who underwent CCTA for typical angina were assigned into two groups based on the modified Duke index: group 1 – patients with low index ≤ 3 (n=107) and group 2 – patients with high index > 3 (n=65). Demo-graphic, clinical and CCTA data were collected for all patients, and FAI analysis of coronary in-flammation was performed. Results: Patients with increased values of the modified Duke index were significantly older compared to those with a low index (61.83 ± 9.89 vs. 64.78 ± 8.9; p = 0.002). No differences were found between the two groups in terms of gender distribution, hypertension, hypercholesterolemia or smoking history (all p > 0.5). The FAI score was significantly higher in patients from group 2, who presented a significantly higher score of inflammation compared to the patients in group 1, especially at the level of the right coronary artery (FAI score 20.85 ± 15.80 vs. 14.61 ± 16.66; p = 0.01 for the right coronary artery, 13.85 ± 8.04 vs. 10.91 ± 6.5; p = 0.01 for the circumflex artery, and 13.26 ±10.18 vs. 11.37 ± 8.84; p = 0.2 for the left anterior descending artery). CaRi-Heart® analysis identified a significantly higher risk of future events among patients with a high modified Duke index (34.84 % ± 25.86 % versus 16.87 % ± 15.80 %; p

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Mast cells are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, mast cells act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. Mast cells originate from bone marrow progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating in heterogeneous tissue-specific subsets. Even though mast cell activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of mast cell biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand mast cell origin and differentiation as well as the phenotype and functions within different tissues, including the gut. This review recapitulates how single cell transcriptomic studies provided insight into mast cell development as well as into the functional role of intestinal MC subsets in health and disease.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects: antioxidant, anti-inflammatory and immunomodulatory, which involves inhibiting molec-ular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential, analysis of cyto-kine, protein and gene expression were investigated in the head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified mor-phology, inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in G2/M and S. A decrease in cell migration was also observed, and decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IF-y and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anti-cancer effects on tumor cells, and could be a promising natural treatment by regulating signaling pathways associated with head and neck cancer.

Chitinase 3-like 1 （also known as CHI3L1 or YKL-40）is a mammalian chitinase that has no enzymatic activity, but has the ability to bind to chitin, the polymer of N-acetylglucosamine (GlcNAc). Chitin is a component of fungi, crustaceans, arthropods including insects and mites, and parasites, but is completely absent from mammals, including humans and mice. In general, chitin-containing organisms produce CHI3L1 to protect the body from exogenous pathogen as well as hostile environments, and it was thought that it has a similar effect in mammals. However, recent studies have revealed that CHI3L1 plays a pro-inflammatory role by inducing anti-apoptotic activity in epithelial cells and macrophages. Under chronic inflammatory conditions such as inflammatory bowel disease and chronic obstructive pulmonary disease, many groups already confirmed that the expression of CHI3L1 is significantly induced on the apical side of epithelial cells, and activates many downstream pathways involved in inflammation and carcinogenesis. In this review article, we will summarize the expression of CHI3L1 under the chronic inflammatory conditions in various disorders and would like to discuss the potential roles of CHI3L1 in those disorders on various cell types.

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

Chronic kidney disease (CKD) affects approximately 12% of the global population posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of CKD contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in non-dialysis dependent stage 5 CKD patients using semitargeted metabolomics. In a prospective observational design involving 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5’-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (N-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in CKD, shedding light on cellular energy production and offering insights for further clinical validation.

The studies regarding macrophage lncRNAs described in this review can help provide valuable information for developing treatments for various pathological conditions involving macrophages. Over the past century, molecular biology's focus has transitioned from proteins to DNA, and now to RNA. Once considered merely a genetic information carrier, RNA is now recognized as both a vital element in early cellular life and a regulator in complex organisms. Long noncoding RNAs (lncRNAs), which are over 200 bases long but do not code for proteins, play roles in gene expression regulation and signal transduction by inducing epigenetic changes or interacting with various proteins and RNAs. These interactions exhibit a range of functions in various cell types including macrophages. Notably, some macrophage lncRNAs influence the activation of NF-κB, a crucial transcription factor governing immune and inflammatory responses. Macrophage NF-κB is instrumental in the progression of various pathological conditions including sepsis, atherosclerosis, cancer, autoimmune disorders, and hypersensitivity. It orchestrates gene expression related to immune responses, inflammation, cell survival, and proliferation. Consequently, its malfunction is a key contributor to the onset and development of these diseases. This review summarizes the role of lncRNAs that regulate NF-κB in macrophage activation and inflammation, especially focusing on their implications in human diseases and their potential as therapeutic targets

Radiotherapy is a crucial treatment for head and neck malignancies, but it usually leads to sensorineural hearing loss (SNHL). Changes in the immune microenvironment and sensorial neuroepithelium of the inner ear after radiation exposure remain poorly understood. This study investigated cochlear morphology and macrophages in the inner ear after high-dose irradiation. The heads of 8-week-old Cx3cr1GFP/+ heterozygous male mice were irradiated with 30Gy X-rays and biological samples were taken on the 1st, 7th, and 10th days after irradiation. Auditory brainstem responses were used to assess auditory function in mice. The changes of basal membrane hair cells, spiral ganglion (SGN), and inner ear macrophages were observed using hematoxylin-eosin (HE) staining and immunofluorescence staining. The expression of inflammatory mediators in the inner ear was detected by reverse transcription-polymerase chain reaction (RT-PCR) in cochlear tissue. As a result, there was no significant hair cell loss after high doses of radiation, but the mice developed full-frequency hearing loss on day 10 when HE staining revealed SGN atrophy and immunofluorescence revealed decreased neurofilament expression. The number of macrophages in the inner ear decreased over time. RT-PCR showed that cochlear inflammatory factors and chemokines were briefly up-regulated on the first day after irradiation and then decreased over time. In summary, high-dose irradiation causes acute SNHL that does not involve hair cell loss and may be associated with SGN changes. Radiation-induced SNHL is accompanied by a reduction in cochlear macrophages and changes in the immune microenvironment, but the relationship between the two has yet to be explored.

Anti-inflammatory agents are widely used for the treatment of inflammatory diseases. Nevertheless, the associated side effects of available drugs make necessary the search for new anti-inflammatory conditions. Here, we investigated the anti-inflammatory activity of solidagenone. Initially, we observed that a single dose of 30, 60 or 90 mg/Kg of solidagenone did not result in mortality or elicit any discernible signs of toxicity in the animals. At the same doses, solidagenone promoted a significative reduction in the migration of neutrophils in an acute peritonitis model and decreased mortality in a lipopolysaccharide-induced endotoxic shock model. Interestingly, treatment with solidagenone conferred a protective effect against leukopenia and thrombocytopenia, hematological disorders commonly observed in sepsis conditions. In addition, treatment with all the doses of solidagenone promoted a significative reduction in nitric oxide, TNF-α, and IL-1β relative to the LPS-stimulated vehicle-treated cultures. Furthermore, gene expression and in silico analyses also supported the modulation of NF-κB pathway by solidagenone. Finally, in silico pharmacokinetics prediction indicated a favorable drugability profile for solidagenone. Taken together, the findings of the present investigation show that solidagenone exhibits significant anti-inflammatory properties in acute experimental models, potentially through the modulation of NF-κB signaling pathway.

Arrhythmogenic cardiomyopathy is a primary genetic disease caused by mutations of the desmosome genes. Ever since the introduction of new imaging criteria, like cardiovascular magnetic resonance, the diagnosis of arrhythmogenic cardiomyopathy is more challenging as left ventricular or biventricular variants may cause resemblance with other cardiomyopathies or myocarditis. Not only this, but they may also share an acute phase that might determine even more confusion and misdiagnosis which can influence prognosis and outcome. In this case report we present a 31-year-old patient with multiple clinical pictures: acute chest pain, new onset of heart failure and arrhythmia symptoms which determined a dynamic change in clinical diagnosis and management, ultimately taking into consideration arrhythmogenic cardiomyopathy. Through the article we try to emerge and explain common pathophysiological pathways shared by arrhythmogenic cardiomyopathy and other clinical entities with a special focus on inflammation. The final question remains: “If there is more than one heart disorder that eventually will lead to the same clinical picture, one could not but wonder if arrhythmogenic cardiomyopathy is rather a syndrome than a specific condition?”

This study explored the effects of pBD114 (porcine β-defensin 114) on inflammatory response. The results in RAW264.7 cells showed that 100 μg/mL of pBD114 significantly increased the concentrations of TNFα and IL-10, and 10 μg/mL of pBD114 significantly decreased the concen-tration of TNFα in LPS-induced RAW264.7 cell cultures at 10 ng/mL. These results suggest that pBD114 can exhibit pro-inflammatory or anti-inflammatory activities under certain conditions. RNA-seq analysis was performed to gain further insight into the effects of pBD114 on the in-flammatory response. Among pBD114 promoting RAW264.7 pro-inflammatory response, pBD114 significantly up-regulated 1170 genes and down-regulated 724 genes. KEGG enrichment found that the DEGs were significantly enriched in immune- and signal-transduction-related signaling pathways. PPI and KDA analyses revealed that Bcl10 and Bcl3 were the key genes. In addition, pBD114 significantly up-regulated 12 genes and down-regulated 38 genes in the an-ti-inflammatory response. KEGG enrichment analysis revealed that the DEGs were mainly en-riched in the "Cytokine-cytokine receptor interaction" signaling pathway, and PPI and KDA analyses showed that Stat1 and Csf2 were the key genes. The results of qRT-PCR verified those of RNA-seq. In vivo mice tests also confirmed the pro- or anti-inflammatory activity of pBD114. Although the inflammatory response is a rapid and complex physiological reaction to noxious stimuli, this study found that pBD114 plays an essential role in the inflammatory response mainly by acting on genes related to immunity, signal transduction, signaling molecules, and interactions.

Several chronic diseases derive from metabolic, genetic, or inflammatory causes and often these causes are interconnected. Pharmacological treatments, although effective, often lead to unpleasant side effects. In this context, preventive approaches are of growing interest. The literature data of recent years support that the dietary intake of bioactive compounds can positively influence the biological functions of an organism. Among the bioactive compounds in the diet, polyphenols are widely recognized for their beneficial effects on health, as useful compounds for preventing/combating a series of pathologies related to lifestyle, metabolism, and aging. The artichoke (Cynara scolymus L.), a member of the Asteraceae family, is widely used in the food and herbal medicine fields for its beneficial properties. Artichokes are rich in polyphenols (including cynarin), flavonoids and their derivatives, and, for this reason, they have aroused interest in their pharmacological properties. The best-known activity of polyphenols is antioxidant activity. Through it, they help to neutralize free radicals, preventing cellular damage and the subsequent risk of conditions such as cancer, diabetes, and heart disease. Related to the antioxidant action we find the anti-inflammatory activity. This is an important benefit since chronic inflammation is a cause or contributory cause of many chronic diseases. Although many scientific results are of great interest and potential, there are still gaps to be filled. In this review, we report and discuss new insights providing documented evidence regarding the benefits of the artichoke compounds and their possible use to support the pharmacological treatment of pathologies associated with inflammation.

CLIPPERS which stand for Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a chronic inflammatory disorder of the central nervous system. The aetiology of CLIPPERS remains unclear, although its pathogenesis shows immune-mediated processes. The diagnosis of CLIPPERS is challenging without a specific biomarker hence, it is important to consider if both the clinical and radiological features are consistent with the diagnosis, or rather any other disease that mimics CLIPPERS. The Authors present a case of a 40-year-old Female patient diagnosed with CLIPPERS syndrome in India. Differential diagnosis, clinical and MRI characteristics of CLIPPERS syndrome, and treatment approaches are discussed.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, is a disease of chronic inflammatory conditions of the intestinal tract due to disturbance of the inflammation and immune system. Symptoms of IBD include abdominal pain, diarrhea, bleeding, reduced weight, and fatigue. In IBD, the immune system attacks the intestinal tract's inner wall, causing chronic inflammation and tissue damage. In particular, IL-6 and IL-17 act on immune cells, including T cells and macrophages, to amplify the immune responses so that tissue damage and morphological changes occur. Of note, excessive calorie intake and obesity also affect the immune system due to inflammation caused by lipotoxicity and changes in lipids supply. Similarly, individuals with IBD have alterations in liver function after sustained high-fat diet feeding. In addition, excess dietary fat intake, along with alterations in primary and secondary bile acids in the colon, can affect the onset and progression of IBD because inflammatory cytokines contribute to insulin resistance; the factors include the release of inflammatory cytokines, oxidative stress, and changes in intestinal microflora, which may also contribute to the disease progression. However, interfering with de novo fatty acid synthase by deleting the enzyme acetyl-CoA-carboxylase 1 in intestinal epithelial cells leads to the deficiency of epithelial crypt structures and tissue regeneration, which seems to be due to Lgr5+ intestinal stem cell function. Thus, conflicting reports exist regarding high-fat diet effects on IBD animal models. This review will focus on the pathological basis of the link between dietary lipids intake and IBD and cover currently available pharmacological approaches.

Background: Polycystic ovary syndrome (PCOS) is a common reproductive and endocrinological disease characterized by ovulatory dysfunction, polycystic ovaries, and hyperandrogenism. Adipokines are believed to contribute to developing PCOS and its accompanying metabolic complications such as dyslipidemia, insulin resistance, and cardiovascular diseases. Oncostatin M (OSM), a novel adipokine, plays a role in oogenesis, lipogenesis, and inflammation and may contribute to PCOS pathogenesis and its related metabolic problems. Methods: In this case-control study, the patients were grouped in a 1:1 ratio into either the PCOS (n = 32) or the control group (n = 32). Blood samples were obtained between the 3rd and 5th days of the menstrual cycle. Serum levels of fasting glucose, insulin, C-reactive protein (CRP), low-density lipoprotein, high-density lipoprotein, triglyceride, white blood cell count, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, total testosterone, prolactin estradiol, and OSM were analyzed. Results: OSM levels were significantly lower, but CRP levels were substantially higher in the PCOS group than in the control group (p = .002, p = .001, respectively). OSM was inversely correlated with total cholesterol, non-high-density lipoprotein cholesterol, fasting glucose, and the luteinizing hormone/follicle-stimulating hormone ratio (ρ = .329, p = .017; ρ = .386, p = .005; ρ = .440, p = .001; ρ = .316, p = .023, respectively). Conversely, there was no correlation between OSM and total testosterone level (ρ = .220; p = .118). In the context of inflammation and metabolic parameters, OSM was inversely correlated with CRP, Homeostatic Model Assessment for Insulin Resistance score (HOMA-IR), and low-density lipoprotein cholesterol (LDL) (ρ = .353, p = .019; ρ = .275, p = .048; ρ = .470, p &lt; .001, respectively). The performance of Oncostatin M for diagnosing PCOS showed 50% sensitivity, 75% specificity, and 63% accuracy (p = .009) in ROC curve analysis. Conclusions: Plasma OSM levels were considerably lower in patients with PCOS than in the control group, and this was inversely correlated with the hormonal and metabolic parameters of PCOS. Thus, OSM may be a novel therapeutic target for PCOS and metabolic complications.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibro-blast-like cells which play important roles in tissue repair, inflammation, and immune modula-tion. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in the last years as key regulator of tumor microenvironment. Indeed, they are now con-sidered as active players in the pathophysiology of hematologic malignancies rather than passive by-standers in hematopoietic microenvironment. Once the malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progres-sion. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been showed that stromal cells themselves play a major role in several hematological malig-nancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterpart and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt the tumor/MSCs coupling. The present review will focus on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer pro-gression.

Inflammation is natural protective response of the body tissue caused by various stimuli. Macrophages start and control the inflammatory response. Microalgae have high value of ingredients including carotenoids which are well known for anti-inflammatory properties and used for various products in functional food industries. A green microalgal, Tetraselmis species contains a various type of carotenoids such as lutein, violaxanthin, astaxanthin, fucoxanthin, α-carotene and β-carotene. Therefore, we studied whether carotenoids isolated from Tetraselmis sp. with different culture conditions in Raw 264.7 cells and zebrafish (Danio rerio) have an anti -inflammatory effect. Carotenoid extracts of natural seawater (NS) and magma seawater (MS) showed inhibitory activity of nitric oxide (NO) overproduction without toxicity. In addition, carotenoid extracts of NS and MS inhibited pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 1β and IL-6. Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, which are inflammatory mediators also decreased by pretreatment of NS and MS. Carotenoid extracts of NS and MS pretreatment also reduced phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kB (NF-kB). In conclusion, the carotenoid extract of Tetraselmis sp. has an anti -inflammatory effect and can be potential industrial ingredient.

The importance of various markers such as sclerostin, Dickkopf-1 (DKK-1), Irisin, receptor activator of NF-kB ligand (RANKL), and Vitamin D have been well studied in bone metabolism. Additionally, inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and Interleukine-6 (IL-6) have been identified to hinder muscle protein synthesis, leading to the loss of muscle and strength. However, a research gap exists in the understanding their role in muscle function and physical activity. Therefore, this study aims to explore the serum levels of sclerostin, DKK-1, irisin, IL-6, RANKL, Vitamin D, and TNF-α and assess their relationships with upper and lower body strength in young adults. In this study, 38 college-aged students 18-23 years participated and completed the protocols. The participants’ lower and upper body strength were assessed by the vertical jump test (Just Jump, Probotic, AL) with a Tendo FitroDyne (Tendo Sports Machines, Trencin, Slovak Republic) and handgrip (HG) dynamometry (Takei Scientific Instruments, Yashiroda, Japan), respectively. Fasting morning blood samples were analyzed for serum levels of the biomarkers by ELISA. The results indicate significant sex differences in sclerostin, DKK-1, irisin, and vitamin D levels (p<0.05). Furthermore, a positive association was observed between sclerostin, DKK-1, and vitamin D, with lower body muscle performance variables (p<0.05). Conversely, a significant negative correlation was observed between TNF-α and upper-body muscle performance variables (p<0.05). The results suggest that these markers may have a distinct effect on muscle performance, underscoring the need for further investigation to elucidate the concept of muscle-bone crosstalk.

Capsaicin, a lipophilic, volatile compound, is responsible for the pungent properties of chili peppers. In recent years, a significant increase in investigations into its properties has allowed the production of new formulations and the development of tools with biotechnological, diagnostic, and potential therapeutic applications. In this way, the possible clinical application of such compound is expanding every year. This opinion article aims to provide a synthesis of recent findings regarding the mechanisms by which capsaicin participates in the control of non-communicable diseases such as obesity, diabetes, and dyslipidemia. This opinion review also discusses the recent findings and clinical studies of the use of capsaicin in body weight control.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (PNE), eosinophil to lymphocyte ratio (ELR) and eosinophil to neutrophil to lymphocytes ratio (ENLR) before and after can-nabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were includ-ed in the study. T. gondii, PNE, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest PNE (p = .02), ELR (p = .03) and ENLR levels (p = .031) and highest increase of PNE (p = .044), and ENLR (p = .036) levels were found in patients after cannabis cessation only in the Toxo+ group. At four weeks, significant interactions between cannabis and T. gondii status for PNE (p = .038), and for ENLR (p = .043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = .049). After cannabis cessation, we found a positive correlation between negative symptoms and PNE levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patient after cannabis cessation.

Background and Objectives: Stroke is a main leading cause for mortality and morbidity worldwide. Treat-ment of this pathology is still under development and its risk factors remain the main target to be reached. Therefore, we aim to determine the role of interleukin 1 beta in atheromatosis, as risk factor for stroke and the reole of this biomarker in stroke prognosis. Materials and Methods: The study conducted enrolled 56 patients diagnosed with ischemic stroke in the anterior (AVT) and posterior vascular territory (PVT). All patients had venous blood collected at admission and 7 days after the onset of the cerebral ischemia in order to determine plasma concentration for interleukin 1 beta. At the same time an extracranial carotid ultrasound was performed. Results: Interleukin 1 beta collected at admission was positively correlated with NIHSS at admission (Pearson index 0,424) and both measurements were corelated with carotid stenosis (Spearmen correlation index 0,529, respectively 0,653). Conclusion: Interleukin 1 beta could be a reliable biomarker for stroke prognosis and carotid atheromatosis development.

To date, recanalization interventions are the only available treatments for ischemic stroke patients, however, there are no effective therapies for reducing stroke-induced neuroinflammation. We recently reported that H+ extrusion protein Na+/H+ exchanger-1 (NHE1) plays an important role in stroke-induced inflammation and white matter injury. In this study, we tested the efficacy of two potent NHE1 inhibitors, HOE642 and Rimeporide, with a delayed administration regimen starting at 24 h post-stroke in adult C57BL/6J mice. Post-stroke HOE642 and Rimeporide treatments accelerated motor and cognitive function recovery without affecting the initial ischemic infarct, neuronal damage or reactive astrogliosis. However, delayed administration of NHE1 blockers after ischemic stroke significantly reduced microglial inflammatory activation while enhanced oligodendrogenesis and white matter myelination, with increased proliferation and decreased apoptosis of the oligodendrocytes. Our findings suggest that NHE1 protein plays an important role in microglia-mediated inflammation and white matter damage. Pharmacological blockade of NHE1 protein activity reduced microglia inflammatory responses and enhanced oligodendrogenesis and white matter repair, leading to motor and cognitive function recovery after stroke. Our study reveals the potential of targeting NHE1 protein as therapeutic strategy for ischemic stroke therapy.

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.

Background: The systemic inflammatory index (SII) is a new inflammatory marker that has been the subject of various studies in diseases with chronic inflammation. Diabetic nephropathy is also a disease that goes with chronic inflammation. We aimed to evaluate the relationship be-tween SII and diabetic nephropathy. Methods: Patients with diabetes who applied to our outpatient clinic are included in the study. Diabetic patients are divided into two groups: those with diabetic nephropathy and those with-out. In addition, healthy individuals who applied to our clinic for general check-ups during these dates are included as control group. The SII values and other characteristics of the three study groups are compared. Results: The median SII value for those with DKI was 584 (178-4819); for those without DKI, it was 282 (64-618); and for the control group, it was 236 (77.5-617) (p<0.001). SII was significantly and positively correlated with BMI, weight, blood glucose, HbA1c, CRP and creatinine, and neg-atively correlated with glomerular filtration rate (GFR) value. The SII value higher than 336 has 75% sensitivity and 70% specificity in detecting DKI. Conclusion: The SII value could predict diabetic kidney injury in diabetics and it could be used as an adjunctive diagnostic tool.

Background: In this paper, it was aimed to evaluate the biomarker potential as well as the effect of the prognostic nutritional index (PNI), which is calculated using the albumin level reflecting nutritional status and lymphocyte count reflecting immune status, in determining the prognosis of metastatic castration-sensitive prostate cancer (mCSPC). Methods: This retrospective observational study included the complete data of 108 patients with mCPSC who were treated for at least three months between January 1, 2010, and June 1, 2021. The relationship between cancer specific survival (CSS), overall survival (OS), progression free survival (PFS) and PNI was evaluated. Kaplan-Meier method for OS, PFS, and CSS, as well as univariate and multivariate Cox regression models were used in statistical analyses. Results: The median age of 108 patients included in the study was 68.54 (61.05-74.19) years. While 71.3% (n = 77) of the patient population were high-volume according to CHAARTED, 52.8% (n = 57) were high-risk based on LATITUDE. 49.75 was determined as the best cut-off point for the PNI. OS (months) was found to be significantly lower in patients with low PNI (median: 34.93, 95% CI: 21.52–48.34) compared to patients with high PNI (median: 65.60, 95% CI: 39.36–91.83) (p=0.016). Patients with high PNI (median: 48.20, 95% CI: 34.66–61.73) had significantly better CSS (months) than patients with low PNI (median: 27.86, 95% CI: 24.16–31.57) (p=0.001). Conclusions: PNI calculated at the time of diagnosis strongly predicts OS and CSS but not PFS in patients with mCSPC.

Leukotrienes are proinflammatory mediators that participate in the process of atherogenesis and contribute to the development of symptomatic peripheral arterial disease. The aim was to evaluate the relationship between leukotriene E4 (LTE4) and B4 (LTB4) with parameters reflecting endothelial vascular function in patients with chronic lower limb ischemia. This prospective observational study enrolled 50 consecutive patients undergoing endovascular treatment due to chronic lower limb ischemia (Rutherford 3). All participants were followed-up for one year (after 1, 3, 6 and 12 months), with a sequential assessment of urinary LTE4 and LTB4, as well as measures of endothelial and vascular function: Flow-Mediated Dilatation (FMD), Intima-Media Thickness (IMT), corrected Augmentation Index (AI75), Shear Rate (SR), Ankle-Brachial Index (ABI), Toe-Brachial Index (TBI). There was a significant relationship between LTE4 and measures of vascular function: FMD (R2 = 0.69, P&lt;0.001), IMT (R2=0.12, P&lt;0.01), AI75 (R2=0.43, P&lt;0.001), SR (R2=0.48, P&lt;0.001). Similar findings were noted for LTB4: FMD (R2=0.47, p&lt;0.001), IMT (R2=0.23, P&lt;0.001), AI75 (R2=0.61, P&lt;0.001) and SR (R2=0.33, P&lt;0.001). Alterations in parameters were significantly related: ΔLTE4 vs ΔFMD(R2=0.63, P&lt;0.001), ΔSR (R2=0.42, P&lt;0.001) and ΔLTB4 vs AI75(R2=0.40, P&lt;0.001), SR(R2=0. 29, P&lt;0.001). We conclude, that increasing concentrations of LTE4 and LTB4 are associated with impairment of vascular and endothelial function, which may lead to worse endovascular treatment clinical outcomes.

The assessment of the prevalence of Subclinical Mastitis (SCM) in dairy farms is essential to validate the health status of the mammary gland. The aim of the study was to assess the prevalence of SCM in dual purpose livestock systems in Arauca, Colombian Orinoquia, through the analysis of the values found by the field diagnostic tests California Mastitis Test (CMT) and Electric Conductivity (EC). Milk samples were taken from the individual mammary quarters of 481 cows. The general prevalence, per affected room and the total number of rooms was determined according to the values obtained for each test using two methods of analysis. An ANOVA was performed to determine the difference between prevalence’s, a correlation analysis, and an analysis of sensitivity and specificity. The general prevalence was similar between the tests (CMT = 31.4%; EC = 29.7%) (p > 0.05). The prevalence of the total quarters was lower with EC (11.3% vs 14.2%) (p < 0.05). The correlations between tests were significant, but with low values (rs = 0.20-0.25). CMT and EC test concordance showed a sensitivity between 0.35-0.45 and a specificity of 0.75-0.90. The two tests showed positive results in detecting the same animals with or without the presence of the infection, although some animals that were positive for one test were not positive for the other test. The test EC classified animals and their quarters as SCM positive or negative in a more similar way to that obtained with CMT. The two diagnostic tests showed a general low prevalence of SCM in the livestock systems evaluated.

Background: Fabry disease cardiomyopathy (FDCM) has manifested some resistance to enzyme replacement therapy (ERT) particularly in its advanced phase. Recently myocardial inflammation of autoimmune origin has been demonstrated in FDCM. Aims: Aim of the study is the assessment of circulating anti-globotriaosylceramide (GB3) antibody as biomarker of myocardial inflammation in FDCM. Its sensitivity was based on the evidence of overlapping myocarditis at left ventricular endomyocardial biopsy. Methods and Results: From January 1996 to December 2021, 85 patients received in our Department the histological diagnosis of FDCM and 48 (56.5%) of them had an overlapping myocardial inflammation with negative PCR for the common cardiotropic viruses, positive anti-heart and anti-myosin abs. The presence of anti-GB3 antibodies was evaluated with an Elisa assay (BioGeM scarl Medical Investigational Research, MIR - Ariano Irpino, Italy) in the FDCM patients and compared with controls of healthy individuals. Circulating levels of anti-GB3 autoantibodies were compared with the presence or absence of myocardial inflammation at histology and with the severity of FDCM. The assay results showed that 42 out of 48 FDCM subjects with myocarditis were positive for anti-Gb3 antibodies while 30 out of 37 FDCM patients without myocarditis had negative anti-GB3 antibodies, with a sensitivity of 87.5 % and a specificity of 83.5%. Conclusions: The present study suggests a potential positive role of antiGB3 antibodies as marker of overlapping cardiac inflammation in patients with FDCM.

White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue that’s primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression. The role of adiposity and systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is still not clear. This review aims to evaluate the emerging evidence on the crosstalk between adiposity and the immune-tumour microenvironment in BC, its progression and treatment resistance. Adiposity, and by extension subclinical inflammation, are associated with metabolic dysfunction and changes in the immune-tumour microenvironment in BC. In oestrogen receptor positive (ER+) breast tumours, it is proposed that these changes are mediated via a paracrine interaction between macrophages and preadipocytes leading to elevated aromatase expression and secretion of pro-inflammatory cytokines and adipokines in the breast tissue in patients who are obese or overweight. In HER2+ breast tumours, WAT inflammation has been shown to be associated with resistance to trastuzumab mediated via MAPK or PI3K pathways. Furthermore, adipose tissue in patients with obesity is associated with upregulation of immune checkpoints on T-cells that is partially mediated via immunomodulatory effects of leptin and has been paradoxically associated with improved responses to immunotherapy in several cancers. In conclusion, evidence suggests that body composition and metabolic status are associated with patient outcomes. To optimise patient stratification and personalisation of treatment, prospective studies are required to evaluate the role of body composition and metabolic parameters in metabolic immune reprogramming with and without immunotherapy in patients with BC.

There is disagreement on the associations between chorioamnionitis and pneumonia/sepsis, respiratory distress syndrome (RDS), and bronchopulmonary (BPD)dysplasia, three pulmonary outcomes of concern for preterm newborns. Determining clear correlations is challenging due to the intricacy of the prenatal, postnatal, and therapeutic practices that affect the diagnosis of RDS, pneumonia/sepsis, and BPD, two long-term outcomes, as well as their short- and long-term consequences. Owing to the interconnected nature of the variables, the vaguely defined fetal exposures, and the imprecise identification of disorders like RDS and BPD, multivariant studies of huge data sets are unreliable methods for defining associations. On the other hand, research using animal models offers reliable data regarding the effects of exploratory chorioamnionitis on the fetal lung. Understanding the clinical intricacy and the experimental consequences of chorioamnionitis together will help us understand on the impact on the fetal lung .

Secretory leucoprotease inhibitor (SLPI) has multifaceted functions, including inhibition of protease activity, antimicrobial functions, and anti-inflammatory properties. In this study, we show that SLPI plays a role in controlling pulmonary P. aeruginosa infection. Mice lacking SLPI were highly susceptible to P. aeruginosa infection, however had no difference in bacterial burden. Utilising a model of P. aeruginosa LPS-induced lung inflammation, human recombinant SLPI (hrSLPI) administered intraperitoneally suppressed the recruitment of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and resulted in reduced BALF and serum levels of inflammatory cytokines and chemokines. This anti-inflammatory effect of hrSLPI was similarly demonstrated in a systemic inflammation model induced by intraperitoneal injection of LPS from various bacteria or lipoteichoic acid, highlighting the broad anti-inflammatory properties of hrSLPI. Moreover, in bone-marrow-derived macrophages, hrSLPI reduced LPS-induced phosphorylation of p-IkB-α, p-IKK-α/β, p-P38, demonstrating that the anti-inflammatory effect of hrSLPI was due to the inhibition of the NFB and MAPK pathways. In conclusion, administration of hrSLPI attenuates excessive inflammatory responses and is therefore, a promising strategy to target inflammatory diseases such as acute respiratory distress syndrome or sepsis and could potentially be used to augment antibiotic treatment.

Uterine fibroid (UF) is a tumour in some parts of the uterus, which introduces health challenges or death due to failed surgery among women globally. This study was designed to ascertain the involvement of micro-nutrients, inflammation, and antioxidant enzymes in the UF development to gain further insights and provide a strategy for managing the disease. One hundred ninety reproductive-aged women were recruited and classified equally into case and control subjects. The supernatant obtained from excised tissues from the fibroid and the normal samples from the adjacent myometrium were assessed for the selected biochemical parameters with standard methods. The levels of vitamin A and sodium between 26-35 years; vitamins D, E, zinc, and selenium between 46-55 years; and vitamin E at 56 years and above significantly decreased (p&lt;0.05). Interleukin-2 (IL-2) level significantly increased (P &lt; 0.05) among the case between 36-45 years. An increase in the activity of glutathione-s-transferase and the reduction in glutathione peroxidase activity and vitamin A level in the uterus between 26-45 years were the most pronounced significant findings (p&lt;0.05) recorded. Prolonged vitamin A deficiency coupled with excess sodium salts facilitating inflammation induced by IL-2 are critical factors for UF development.

The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity that may ultimately result in cancer. The process is described as the result of dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potential cancerous behavior. In support of the hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic model for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed against recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. Subsequently, is proposed an epigenetic landscape for their progression and a potential mechanism to restrain the degree of dedifferentiation and malignant behavior. Finally, is suggested a novel understanding of the involution and carcinogenesis of tissues associated with aging as a perspective that might inspire integrative approaches in the study and management of chronic diseases.

Chronic heart failure (CHF) results when heart cannot constantly supply the body tissues with oxygen and required nutrients, and it can be categorized as heart failure (HF) with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). There are different causes and mechanisms of the HF pathogenesis; however, the inflammation can be regarded as one of the factors promoting both HFrEF and HFpEF. Monocytes, a subgroup of leucocytes, are known as cellular mediators in response to cardiovascular injury and are closely related to inflammatory reactions. These cells are a vital component of the immune system and are the source of macrophages, which participate in cardiac tissue repair after injury. However, the monocytes are not homogenous as thought, and thus can present different functions under different cardiovascular disease conditions. In addition, there is still an open question whether the functions of monocytes and macrophages should be regarded as a cause or a consequence in CHF development. Therefore, our aim was to summarize the current studies on the function of various monocyte subsets in CHF with a focus on the role of a certain monocyte subset in HFpEF and HFrEF patients, and the relation to inflammatory markers.

The present study explored the expression of CD62L and CD44 by bovine peripheral blood mononuclear cells (PBMCs) and WC1.1+ γδ T cells under Staphylococcus aureus cell culture stimu-lation. In this study, peripheral blood cells were isolated from ten dairy cows and cocultured with S. aureus. Afterward, the γδ T cell subpopulation and the expression of CD44, CD62L and prolif-erative (Ki67+) cells were evaluated by flow cytometry. Our results showed that the percentages of proliferative PBMCs and WC1.1+ γδ T cells were higher when stimulated with S. aureus. The percentage of CD44+ cells increased in S. aureus-stimulated cultured PMBCs and WC1.1+ γδ T cells, as did the CD44 geometric mean fluorescence intensity (GMFI). The rate of CD62L cells did not differ among groups for either PBMCs or WC1.1+ γδ T cells. A higher GMFI of CD62L in prolif-erative PBMCs than nonproliferative PBMCs upon stimulation with S. aureus was detected, whereas no impact on the GMFI of CD62L was observed in WC1.1+ cells. In summary, our study identified that S. aureus was associated with high expression of CD44 in overall PBMCs and WC1.1+ γδ T cells, and they could generate memory WC1.1+ γδ T cells, preferably central memory cells.