Concentrations Of Proinflammatory Cytokines Research Articles

Obesity as factor of development of metabolic deviations in gestational diabetes

Objective — to evaluate the pathophysiological role of obesity in the development of metabolic disorders in women with gestational diabetes (GD). Materials and methods. 125 pregnant women were examined, including 33 obese patients, 32 pregnant women with GD, and 37 women with comorbidity of GD and obesity. The control group was represented by 23 practically healthy pregnant women. The content of proinflammatory cytokines (interleukin1b (IL‑1b), IL‑6, IL‑17, tumour necrosis factor a (TNFa)), C‑reactive protein (CRP) and glucometabolic profile were determined. Results. An integral analysis of the incidence structure of degrees of obesity by group established a statistically significant increase in degrees of obesity in women with combined pathology. The HOMA‑IR insulin resistance index was statistically significantly higher in obese patients by 1.1 times (p <0.05) compared with isolated GDM and by 2.5 times (p <0.001) compared with the control group, with a combined course of GDM and obesity — by 1.2 times (p <0.001) and 2.7 times (p <0.001), respectively. The indicators of the obesity group and the comorbidity group differed by 1.1 times (p <0.001). The median CRP content in pregnant women with GD and obesity was 8.12 mg/l, in obese patients — 6.95 mg/l, and in patients with GD — 4.47 mg/l. These results exceeded the control values (2.67 mg/l) by 3.04 (p <0.001), 2.6 (p <0.001) and 1.7 (p <0.001) times, respectively. The results of studying the activity of proinflammatory cytokines showed their significant overexpression in all study groups, but the deviations were more pronounced in women with comorbidities of GD and obesity. Correlations were revealed between parameters of the glucometabolic profile and markers of inflammation, as well as strong positive correlations between body mass index and levels of IL‑17 (r=0.91; p <0.01), IL‑6 (r=0.89; p <0.01), IL‑1b (r=0.94; p <0.01), TNF‑α (r=0.88; p <0.01) and CRP (r=0.86; p <0.01) in women with comorbid pathology. Conclusions. The presence of concomitant obesity in women with GD is characterized by the intensification of the meta‑inflammatory phenotype, which is manifested by significantly more pronounced expression of pro‑inflammatory biomarkers — cytokines IL‑1b, IL‑6, IL‑17, TNF‑α, and CRP, and is associated with statistically deeper deviations of the glucometabolic profile, progression of insulin resistance and deterioration of the course of GD compared to isolated pathology.

Rectal mucosal inflammation, microbiome, and wound healing in men who have sex with men who engage in receptive anal intercourse

Abstract Mucosal injury is common during consensual intercourse and induces an inflammatory response that could contribute to pathogen transmission including HIV. Here, we compared mucosal immune and microbiome responses to experimentally induced mucosal injury between men who have sex with men engaging in receptive anal intercourse (MSM-RAI) and men who do not engage in RAI (controls), all without HIV. Rectal mucosal secretions were collected from adult MSM-RAI (n = 19) and controls (n = 6) via anoscopy before and up to eight days after experimentally induced injury. Mucosal healing was evaluated by repeated injury surface area measurements with digital imaging. MSM-RAI demonstrated overall significantly higher concentrations of pro-inflammatory cytokines and a distinct rectal microbiome compared with controls. Wound healing was numerically faster in MSM-RAI but did not meet statistical significance (p = 0.09). Different cytokine injury response patterns were observed between MSM-RAI and controls; however, IL-6 and IP-10 were important mediators in both groups. Microbial guilds, particularly from the Lachnospiraceae and Prevotellaceae families, were associated with rectal mucosal inflammation. This work is the first experimental study of rectal mucosal injury and the immune environment in healthy humans and provides a more nuanced understanding of rectal mucosal inflammation after injury, which can inform our understanding of HIV transmission.

Indexes of systemic inflammation in hemorrhagic stroke with effective blood flow: a dynamic observation

Increasing evidence suggests that stroke is a systemic disease affecting multiple organs. Systemic inflammatory response and immune dysregulation associated with hemorrhagic stroke, may play an important role in brain injury, its recovery, and stroke outcomes. However, it is worth of note that, from our point of view, the classical concepts about inflammation in pathophysiology and general pathology do not entirely meet the needs of modern medical practice. The existence of this problem is also typical for assessing pathogenesis, as well as for optimizing pathogenetic therapy of severe strokes. Therefore, within the framework of this work, a dynamic observation and assessment of pathogenesis in severe intracerebral hemorrhage was carried out using the criteria of a systemic inflammation scale. The study included patients with intracerebral hemorrhage and effective cerebral blood flow. Blood sampling was carried out on days 1-3 and 5-7 after clinical manifestation of intracerebral hemorrhage. To determine markers of systemic inflammation in the blood plasma of patients, the levels of IL-6, IL-8, IL-10, TNFá, procalcitonin, cortisol, myoglobin, troponin I and D-dimers were examined using an enzyme-linked immunosorbent assay. The Kolmogorov–Smirnov test was used to confirm the normal data distribution. Further comparison of quantitative data was carried out using the nonparametric Wilcoxon test for paired comparisons. All results were considered statistically significant at p 0.05. In patients on days 1-3 and 5-7, statistically significant differences were not observed in almost all studied markers of systemic inflammation, except for IL-8 and tumor necrosis factor-á. Such increased contents of pro-inflammatory cytokines may indicate increased systemic inflammation over time in the patients with intracerebral hemorrhage and effective cerebral blood flow. Hence, the condition of such patients may worsen on days 5-7 after manifestations of intracerebral hemorrhage, thus requiring more careful monitoring of patients’ blood counts and therapy aimed at suppression of increasing inflammation.

Сontents of neuroimmunovascular factors and the state of microcirculation of bulbar conjunctiva in post-traumatic stress disorder in veterans of modern combat conflicts

Chronic exposure to multimodal stress, e.g., allostatic overload leads to dysadaptive response of various organs and triggers pathophysiological mechanisms that contribute to development of post-stress disorders in veterans of modern military conflicts. Brain is a key stress response organ, and sustained matching of blood flow to metabolic demands of the brain is ensured by signaling mechanisms of neuroimmunovascular interaction. The purpose of the study was to assess the contents of humoral neuroimmunovascular factors, and the state of microcirculation at the ocular bulbar conjunctiva in post-traumatic stress disorder (PTSD) in veterans of modern military conflicts. Materials and methods: 35 veterans of a special military operation on the territory of Ukraine with a documented diagnosis of PTSD (ICD-10: F43.1; ICD-11: 6B40) aged from 25 to 60 years particioated in the study. Biomicroscopy of the ocular bulbar conjunction was performed using a slit lamp SLR 100 (K. Zeiss, Germany). The levels of following vasoactive factors were determined in blood by ELISA method: vascular endothelial growth factor VEGF (eBioscience test system, BenderMedSystems, Austria); endothelin-1 (BioMedica, Austria). The concentration of nitrites was determined by Gries reaction using the technique of N. Emchenko. The blood cytokine profile was studied with a Luminex Magpix 100 immunoanalyzer (USA), using Bio-Plex multiplex test system (MERZ, Germany), in order to determine IL-6, TNFá. The data were evaluated with SPSS program. Results and discussion: a study of blood microcirculation at the bulbar conjunctiva of veterans with PTSD revealed the predominance of spastic-atonic changes, mainly due to the capillary-venular component, emergence of arterial-venous anastomoses, aneurysms contributing to increase of hypoxic-ischemic changes in brain tissue, dystrophic changes, reduction of cerebral blood flow, being a consequence of vascular remodeling and neovascularization. There is an imbalance of vasoactive molecules in blood, with predominance of vasoconstriction effects associated with increased levels of endothelin-1, a vascular endothelial growth factor along with decreased concentrations of nitrite ions. We have shown increased systemic circulation of pro-inflammatory cytokines IL-6 and TNFá which may promote neuroinflammatory and neurotoxic processes in brain tissue. Conclusion. Development of neurocognitive post-stress disorders occurs in presence of accumulating “allostatic cargo”, being accompanied by maladaptive changes in the microcirculation of brain tissue along with disturbances in angioarchitecture, imbalance of vasoactive molecules, and increased contents of pro-inflammatory cytokines.

Diagnostic value of interleukins 23 and 17 in the assessment of ulcerative colitis severity

Background. Ulcerative colitis (UC) is a chronic bowel disease with a complex aetiology that includes immune, genetic and environmental factors. Its progression and severity vary greatly, suggesting that different cytokine pathways may be responsible for the heterogeneity of clinical outcomes. The purpose of the study was to investigate the state of cytokine regulation of inflammation depending on the severity of UC. Materials and methods. We examined 32 patients with UC who were treated at the Department of Intestinal Diseases of the State Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”. Patients were divided into groups depending on disease severity determined by the Mayo index: moderate UC — 24 individuals, severe UC — 8 patients. Serum levels of interleukin (IL) 17 and IL-23 were determined by enzyme-linked immunosorbent assay. The study was performed according to the instructions for each test kit. Statistical processing of the results was done using the Statistica 6.1 software package. Results. The content of proinflammatory cytokines in the examined patients with UC was significantly higher than in the control group: IL-17 — by 9.0 times (р < 0.05), the median level of IL-23 — 8.6-fold (р < 0.05). When analysing the data depending on the disease severity, it was found that IL-17 was significantly higher in patients with moderate (by 9.9 times, р < 0.05) and severe UC (by 9.1 times, р < 0.05) than in controls. The median level of IL-23 was significantly higher in moderate (by 8.3 times, р < 0.05) and severe UC (by 13.2 times, р < 0.05) compared to that of the control group. In addition, with severe UC, the concentration of IL-23 was 1.6 times than in moderate UC. A correlation was found between the levels of IL-17 and IL-23 in patients with UC (r = +0.361; p = 0.042). Conclusions. The content of proinflammatory cytokines in UC has reliable differences vs. control group: IL-17 is significantly higher, by 9.0 times (р < 0.05), and IL-23 — by 8.6 times (р < 0.05). It was found that among patients with UC, the level of IL-23 was higher in those with severe course. Thus, quantitative determination of IL-17 and IL-23 levels in the blood serum of patients with UC can be a useful clinical tool for stratification by disease severity and help choose therapy.

IGF2BP2 promotes lung adenocarcinoma progression by regulating LOX1 and tumor-associated neutrophils.

Lung adenocarcinoma (LUAD) is the common form of lung cancer and is prone to distant metastasis. IGF2BP2, an m6A modification regulator, is upregulated in lung cancer tissue, but its specific role within the LUAD tumor microenvironment (TME) is unknown. We explored the role of IGF2BP2 in the progression of LUAD. IGF2BP2 expression in LUAD patient specimens and controls was evaluated through bioinformatics, Western blot, and immunohistochemistry. LUAD subcutaneous and orthotopic xenograft tumor models were established, alongside a co-culture system of tumor-associated neutrophils (TANs) and A549 cells. Functional assays assessed IGF2BP2's role under treatment with JX5, an IGF2BP2 inhibitor. Mechanistic assays explored the interaction between IGF2BP2 and LOX1 in 293T cells. IGF2BP2 was significantly upregulated in LUAD tissues, with higher expression levels predicting worse prognosis for patients (p < 0.001). In subcutaneous and orthotopic xenograft models, treatment with JX5, an IGF2BP2 inhibitor, reduced tumor size, volume, and weight (p < 0.001). JX5 also significantly reduced the concentrations of pro-inflammatory cytokines in peripheral blood (p < 0.01 and p < 0.001). Flow cytometry analysis indicated JX5 reduced CD11b+Ly6G+/CD45+ cells (TANs) in the TME (p < 0.001). Mechanistically, JX5 downregulated LOX1 expression in vivo, and co-culture experiments further demonstrated that IGF2BP2 promotes LUAD progression through LOX1-mediated regulation of TAN activity (p < 0.01 and p < 0.001). Overexpression of LOX1 reversed the inhibitory effects of JX5 on TAN infiltration, tumor cell viability, and apoptosis (p < 0.01 and p < 0.001). Additionally, RNA immunoprecipitation revealed that IGF2BP2 binds to LOX1 mRNA at its m6A modification site, stabilizing LOX1 and enhancing its function in the TME. Knockdown of IGF2BP2 accelerated LOX1 mRNA degradation, confirming its role in maintaining LOX1 stability (p < 0.01 and p < 0.001). IGF2BP2 recognizes and stabilizes LOX1 through m6A modification, contributing to TAN-mediated LUAD progression. Overall, these findings offer new insights into LUAD progression and demonstrate that IGF2BP2 is a key regulator that promotes tumor advancement, highlighting the IGF2BP2-LOX1 axis as a potential therapeutic target for LUAD.

Flow-cytometric Analysis of Reactive Oxygen Species in Blood Cells: A Potential Tool for Predicting Restenosis - Insights from a Cohort Study.

In-stent restenosis (ISR) is a recurrence of a blockage in a section of the coronary artery that has previously been treated with a stent. Molecular/biochemical pathways underlying ISR are not fully understood, but inflammation and reactive oxygen species (ROS) induced oxidative stress play a significant role in the pathogenesis of restenosis. As blood cells are highly sensitive to oxidative stress and blood is readily accessible compared to other tissues, the current study flow cytometrically investigated intracellular ROS and cytokine profile of blood cells as possible markers of restenosis. Flow cytometry is commonly used for detecting ROS and analyzing oxidative stress but so far, it has not been utilized for prediction of ISR. So, the aim of the study was to explore the potential of flow cytometric assessment of ROS levels in the blood cells as predictor of ISR. The study was carried out in a total of 60 patients who had previously undergone coronary artery stent implantation. They were categorized as Group I - Coronary stent implanted patients without restenosis (n=30) and Group II - Coronary stent implanted patients with restenosis (n=30). Sociodemographics, biochemical and angiographic characteristics were assessed. Intracellular ROS and cytokine estimation in blood cells was done by using flow cytometric analysis. Flow cytometric measurements demonstrated a 1.3-fold increase in ROS levels in red blood cells (RBCs) and 2-fold increase in ROS levels in leucocytes in group II as compared to group I. Mean serum concentrations of pro-inflammatory cytokines: tumor necrosis factor-α (33.54 ± 6.48 vs. 20.10 ± 5.61, p <0.001***), interferon-gamma (21.76 ± 4.46 vs. 20.10 ± 5.61, p <0.001***), interleukin 6 (152.56 ± 30.67 vs. 113.95 ± 23.38, p <0.001***) were found to be higher in restenotic patients as compared to the non-restenotic patients. Correlation analysis showed that intracellular ROS levels of RBCs exhibited a significant positive correlation with late lumen loss in restenotic (r=0.71, p <0.01) as well as non-restenotic patients (r=0.59, p <0.01). Similarly, intracellular ROS levels of WBCs exhibited a significant positive correlation with late lumen loss in restenotic (r=0.72, p <0.01) as well as non-restenotic patients (r=0.61, p <0.01). This study highlights the role of increased levels of intracellular ROS in blood cells in the subsequent development of ISR, which can be detected flow cytometrically. The study suggests that intracellular ROS estimation in blood cells may serve as a potential marker for restenosis and their flow cytometric analysis may facilitate the prediction of ISR.

Phytochemicals in the treatment of patients with depression: a systemic review

BackgroundDepression is a complex mental disease whose incidence increases every year; 300 million people worldwide currently suffer from it. Women are more likely to suffer from depression, twice the rate as men. It is one of the few illnesses that can lead to suicide, which makes it very dangerous – currently, 700,000 people die from suicide and it is the 4th most common cause of death in people aged 15-29. The treatment strategies for depression is a big challenge for physicians, pharmacists, scientists and classic remedies cause many side effects. Therefore, natural phytotherapy with herbs can prove to be a good solution. Phytotherapy is a popular treatment method used for centuries in Chinese medicine or Ayurveda.Materials and methodsThe study conducted a comprehensive database search PubMed, ClinicalKey and MedNar covered the years 2015 - 2024 to provide the most up-to-date data. 13 randomized controlled trials and 1 meta – analysis were included in the systematic review.ResultsMany plants show anti-inflammatory, antioxidant and cognitive enhancing effects, which are particularly important in depression. In the treatment of depression, plants such as Crocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. have proven to be effective. They show good effectiveness in human studies and alleviate the symptoms of depression. Herbal products can support classical pharmacotherapy, but this requires further research. Non-commercial clinical trials in the future should provide answers to research questions: at what stage of treatment of patients with MDD will the use of phytochemicals be most appropriate in terms of therapy efficacy and safety for the patient.ConclusionsCrocus sativus L. stigma, Lavandula angustifolia, Hypericum perforatum L. and Curcuma longa L. in modern medicine can help improve the well-being of patients with depression. The use of herbs as an intervention was associated with a decrease in the concentration of proinflammatory cytokines and an overall improvement in the mood of patients. Further research should be undertaken into combining both therapies in order to improve patients’ quality of life and reduce treatment costs.

NK cell-derived exosomes inhibit survival of Mycobacterium tuberculosis by promoting apoptosis in mice

AimTo investigate anti-Mycobacterium tuberculosis (Mtb) influences exerted by natural killer cell-derived exosomes (NK-exo) on mice and to elucidate underlying immunologic mechanisms. MethodsWe established tuberculosis (TB) model in mouse by injecting Mtb H37Ra (1 × 106 colony counting (CFU), i.v.) into tail vein for 14 days. The survival rate of Mtb was assessed through CFU, apoptosis rates were measured utilizing flow cytometry, and inflammation relief was quantified via HE staining. Expressions of apoptosis, inflammation, and pyroptosis-related proteins were quantified by Western blotting and RT-qPCR. ELISA was utilized for detecting inflammatory cytokines production. Intracellular reactive oxygen species (ROS) levels were assessed through DCFH-DA fluorescent probe assay. ResultsNK-exo treatment reduced Mtb load in lung and spleen tissues and alleviated inflammation in mice lung tissues. NK-exo intervention increased protein levels of markers associated with apoptosis, PARP and caspase-3/8/9, downregulating the concentrations of pro-inflammatory cytokines, comprising IL-1β, TNF-α, IL-6, along with protein expressions of biomarkers, ASC, NLRP3, GSDMD, associated to inflammation and pyroptosis. NK-exo also elevated ROS levels without affecting lactate dehydrogenase (LDH) release from macrophages. ConclusionNK-exo exhibits anti-tuberculosis activity in experimental TB mice. The underlying mechanism involve regulating caspase-dependent apoptotic signaling pathway to promote cell apoptosis, as well as modulating NLRP3 signaling pathway to suppress the inflammatory response.

Cerebral natriuretic peptide and systemic inflammation factors in the combined course of community-acquired pneumonia and gastroesophageal reflux disease

Objective: to determine the level of cerebral natriuretic peptide (CNP) and markers of systemic inflammation in the dynamics of treatment of CAP in patients with GERD.Materials and methods: 84 patients with CAP were studied at an average age (42.3±2.9) years, including 44 men and 40 women who were treated in a therapeutic hospital. All patients with VP had a mild course. Among patients with CAP, 48 were diagnosed with GERD (main group), 36 patients had no symptoms of GERD (comparison group 1). Comparison group 2 consisted of 36 patients with GERD without CAP. In addition to conventional examination methods, all patients with CAP and GERD were assessed for CRP, procalcitonin (PCT), BNP (by its stable fragment NTproBNP), interleukins (IL)-1, IL-6, IL-8 at the start of therapy and before discharge.Results: in all patients with CAP in combination with GERD, respiratory and dyspeptic symptoms were noted, along with symptoms of intoxication. Electrocardiography in patients with CAP in combination with GERD diagnosed low voltage voltage of QRS complexes, right ventricular extrasystoles, violations of the processes of repolarization of the left ventricle. During laboratory examination in patients with САP combined with GERD, a significant increase in the level of CRP, PCT, and proinflammatory cytokines was observed, which characterized a pronounced systemic inflammatory syndrome. At the same time, by discharge in patients with CAP combined with GERD, blood levels of CRP and IL-1, IL-6 and IL-8 remained elevated, despite clinical recovery from CAP. Positive correlations were found between CRP and proinflammatory cytokines, which weakened by discharge. In patients with CAP combined with GERD and with only CAP, at the beginning of treatment, the level of NTproBNP was within the reference values, and by discharge it increased by 1.2 times, more significantly in patients with CAP combined with GERD.Conclusions: the clinical course of САP in patients with GERD is characterized by respiratory and dyspeptic syndromes, as well as more frequent ECG changes in the form of extrasystole. In patients with САP combined with GERD, there is a pronounced systemic inflammatory syndrome with a significant increase in the concentration of CRP, PCT and proinflammatory cytokines in the blood compared with patients with САP without GERD. At the same time, by discharge in patients with САP combined with GERD, blood levels of CRP and IL-1, IL-6 and IL-8 remain elevated, despite clinical recovery from САP. An increase in the level of MNUP (according to a stable fragment of NTproBN) in patients with САP combined with GERD, which appeared during clinical recovery from САP, taking into account its pathogenetic role, should be considered as a risk factor for myocardial involvement in the preserved inflammatory process, which determines careful monitoring of the dynamics of CRP, MNUP (NTproBN), proinflammatory cytokines and the state of myocardial infarction in patients with GERD who underwent САP during the dispensary observation.

A cross-section study of the comparison of plasma inflammatory cytokines and short-chain fatty acid in patients with depression and schizophrenia

BackgroundMajor depressive disorder (MDD) and schizophrenia (SCH) are common and severe mental disorders that are mainly diagnosed depending on the subjective identification by psychiatrists. Finding potential objective biomarkers that can distinguish these two diseases is still meaningful.MethodsIn the present study, we investigate the differences in plasma inflammatory cytokines and short-chain fatty acids (SCFAs) among patients with MDD (n = 24) and SCH (n = 24), and gender- and age-matched healthy controls (HC, n = 27) and identify potential plasma biomarkers.ResultsWe found that the concentrations of pro-inflammatory cytokines were increased, whereas the anti-inflammatory cytokines were decreased in both MDD and SCH. Meanwhile, except for an increase in 4-Methylvaleric acid, other SCFAs with statistical differences were reduced in both MDD and SCH. Moreover, potential biomarker panels were developed that can effectively discriminate MDD from HC (AUC = 0.997), SCH from HC (AUC = 0.999), and from each other (MDD from SCH, AUC = 0.983).ConclusionsThese data suggest that alterations in plasma cytokines and SCFAs might be one of the potential features for distinguishing MDD and SCH.Trial registrationChinese Clinical Trial Registry: ChiCTR2100051243, registration date: 2021/09/16.

Вміст цитокінів у слизовій оболонці стравоходу щурів із глутаматіндукованим ожирінням за умов періодичного введення мультипробіотика

Today, the link between obesity and gastroesophageal reflux disease [GERD] is a proven fact. However, there is no information about the condition of the esophageal mucosa (EM) against the background of glutamate-induced obesity (GIO). The aim of our work was to investigate the content of cytokines in the EM of rats with GIO against the background of periodic administration of the multiprobiotic “Symbiter acidophilic®” concentrated (Symbiter). The work was carried out on 30 white non-linear male rats, divided into three groups: the first group was an intact control, the rats of the second and third groups were simulated obesity by administering to them in the neonatal period monosodium glutamate (4 mg/g, dissolved in water for injections in the volume of 8 μl/h subcutaneously on the 2nd, 4th, 6th, 8th, and 10th days after birth. Rats in the third group were periodically injected with Symbiter (140 mg/kg), starting from the first month of life. After reaching the age of 16 weeks, the rats were sacrificed and the presence of obesity was assessed according to the Lee index. Next, the esophagus was cut out and the mucous membrane was examined using a binocular magnifier. The content of cytokines in the mucosal homogenate was determined using enzyme-linked immunosorbent assay. Obesity was recorded in 4-month-old rats after neonatal sodium glutamate administration. In the EM, they did not have visible lesions, but biochemical changes developed, consisting of an increase in the content of pro-inflammatory cytokines IL-1β, TNF-α and IL-12B p40 against the background of a decrease in the content of the anti-inflammatory cytokine IL-4 and a slight increase in another anti-inflammatory cytokine IL-10. That is, we are talking about the inflammatory process at preclinical level. Against the background of the GIO development, the periodic administration of Symbiter to rats led to the normalization of the body weight and to a decrease in the content of pro-inflammatory cytokines and a positive effect on the level of anti-inflammatory cytokines in the EM. Subsequently, the EM inflammatory process in rats with GIO may lead to the development of GERD. Symbiter, having a normalizing effect on the composition of the microflora, prevents obesity, eliminates inflammation, this leads to the normalization of the pro- and anti-inflammatory cytokines ratio in the mucous membrane of the esophagus of rats after neonatal administration of monosodium glutamate.

Effects of Hyperbaric Oxygen Therapy in Treatment on Diverse Diseases

INTRODUCTION: Hyperbaric oxygen therapy (HBOT) indeed holds significant therapeutic potential across various medical conditions, primarily by increasing the concentration of oxygen delivered to tissues under pressure. Saturating tissues with oxygen allows for the effective alleviation of underlying hypoxia, facilitating healing, tissue repair and mechanisms of action leads to reducing concentration of pro-inflammatory acute phase proteins, interleukins, and cytokines. Conversely, HBOT while also boosting levels of growth factors and other cytokines that promote angiogenesis. REVIEW METHODS: The article was complied by analyzing data from PubMed and Google Scholar regarding effects of hyperbaric therapy. THE STATE OF KNOWLEDGE: Studies indicate that HBOT provides numerous opportunities in the treatment of extensive diseases acress various systems. Neurodegenerative disorders involve progressive nerve cell damage leading to motor or cognitive decline, exacerbated by oxidative stress and inflammation. HBOT has shown promise in delaying disease onset by improving mitochondrial dysfunction in motor neuron disease. In case of intestinal obstruction HBOT reduces intestinal gas volume, diameter of obstructed loops, and improves intestinal contractility. Significant benefits have been observed in conditions such as Crohn's disease and ulcerative colitis. Hyperbaric therapy presents potential benefits for the infertility, improving the environment for blastocyst implantation and pregnancy. CONCLUSION: There is no doubt that HBOT has a beneficial impact on treatment of many systems such as the nervous, cardiovascular, digestive, and skeletal. This innovative approach of hyperbaric therapy extends to selected disorders such as neurodegenerative diseases, Crohn's disease, ulcerative colitis, and infertility.

Evaluating the roles of food matrix, lipid micronutrients and bioactives in controlling postprandial hypertriglyceridaemia and inflammation.

Lipids play an important role in human nutrition. Although adequate lipid consumption is necessary for an optimal functioning of the human body, overconsumption of saturated fatty acids can lead to postprandial hypertriglyceridaemia, which triggers the development of atherosclerosis. Important parameters that impact postprandial lipaemia and inflammation are related to the matrix structure and the fat-soluble micronutrient profile of ingested foods/lipids, but the specific effect of these parameters should be further studied, as most of the available studies evaluate their effect at fasting state. This review specifically explores the effects of food structure and fat-soluble micronutrients, from either micronutrient-rich foods or supplements, on postprandial hypertriglyceridaemia and inflammation. The review also highlights the potential of emerging biomarkers such as miRNAs or circulating microvesicles, as an alternative to the widely use biomarkers (e.g. low-density lipoproteins or blood concentration of pro-inflammatory cytokines), to identify inflammation associated with postprandial hypertriglyceridaemia at early stages.

Impact of IL-8 on survival after TARE in HCC: a comprehensive investigation and external validation from the SORAMIC trial.

In the treatment of hepatocellular carcinoma (HCC) with transarterial radioembolization (TARE), identifying reliable biomarkers for predicting survival outcomes remains a critical challenge. We aimed to address this gap by investigating the significance of serum cytokines associated with inflammation as potential biomarkers for the selection of patients for TARE. Our retrospective study involved 161 patients diagnosed with HCC who underwent Y90 radioembolization at our medical center between 2010 and 2020. Serum samples from a subset of 78 patients were retrospectively analyzed to determine the concentrations of pro-inflammatory cytokines. The results from the prospective SORAMIC trial were used for independent validation. With a median overall survival of 36 weeks (range 4-436), our study showed the strongest correlation between 12-week survival and IL-8 levels before treatment (p < 0.001), while other relevant interleukins, interferon-α2, INF-γ, TNF-α and MCP-1 were not associated with survival. IL-8 levels below the cut-off of 190 pg/mL were significantly associated with increased 12-week and 24-week survival, with hazard ratios of 19.01 (95% CI: 2.29-157.89) and 2.57 (95% CI: 1.05-6.31), respectively (p = 0.006 and p = 0.039, respectively). In the adjusted multivariate analysis, the 190 pg/mL cut-off for IL-8 remained independently associated with 12- (p = 0.011) and 24-week survival (p = 0.039). Similarly, the SORAMIC population showed a strong association between IL-8 levels and 36-week survival (p = 0.03). Our study emphasizes the pivotal role of IL-8 as a valuable parameter, demonstrating its potential for predicting treatment outcomes and assessing liver function in patients with HCC undergoing TARE. The robustness of these findings warrants further validation.

Immunothrombosis and plasma fibrinolytic function for pediatric COVID-19: a secondary analysis from the COVAC-TP trial

AbstractThe relationship between fibrinolysis, inflammation, and prothrombotic risk among children hospitalized for coronavirus disease 2019 (COVID-19)–related illness is ill defined. To investigate the association between plasma fibrinolytic capacity and proinflammatory cytokine concentrations among children hospitalized for primary COVID-19 infection and multisystem inflammatory syndrome in children (MIS-C), we hypothesized that cytokine concentrations differ by clinical phenotype and are associated with hypofibrinolysis. We analyzed banked plasma specimens serially collected from children aged <18 years admitted for primary COVID-19 or MIS-C and enrolled in the COVID-19 Anticoagulation in Children–Thromboprophylaxis multicenter trial, an open-label, multicenter, phase 2 clinical trial conducted between July 2020 and May 2021. Plasma coagulative and fibrinolytic function were measured via the clot formation and lysis (CloFAL) assay and modified mini-euglobulin clot lysis assay (ECLA). Interleukin-1β (IL-1β), IL-6, and IL-8, and tumor necrosis factor α were measured by the Meso Scale Discovery assay. Correlations were evaluated using Spearman rank testing. A total of 132 banked plasma specimens from 38 participants (COVID-19: n = 18; MIS-C: n = 20) were analyzed. Overall, increased coagulative function (ie, elevated CloFAL area under the curve) and impaired fibrinolytic function (ie, reduced CloFAL fibrinolytic index [FI] and elevated modified mini-ECLA clot lysis time ratio [CLTR]) were observed but most notably among those with MIS-C. Plasma cytokine concentrations correlated with assay indices of hypofibrinolysis (ie, modified mini-ECLA CLTR and CloFAL FI). In summary, among children hospitalized for COVID-19–related illness, hypercoagulability and hypofibrinolysis are mediated, in part, by inflammation that may contribute to prothrombotic risk. This trial was registered at www.ClinicalTrials.gov as #NCT04354155.

The green formulation of silver nanoparticles for the anticancer and lupus nephritis treatment applications and reducing the inflammatory cytokines in the rat periodontal model

In this study, a novel bio-inspired synthesis for the preparation of Ag NPs by Calendula persica flower extract has been researched. Also, the effects of the recent composite on lupus nephritis by following the TGF-β1 signaling pathway in mice and gingival amounts of IL1-β and TNF-α in the animal periodontal model were determined. To assess the crystal nature, morphology and size of the prepared nanoparticles, X-ray diffraction (XRD), transmission electron microscopy (TEM), ultraviolet–visible (UV–Vis) and field emission-scanning electron microscopy (FE-SEM) analyses were applied in this study. The prepared Ag NPs was employed for its effectiveness against colon cancer cell line (C26). The bio-synthesized Ag NPs had also cytotoxic property versus colon cancer based on MTT protocol. Collectively, the Ag NPs fabricated by biological way has potential applications in inflammatory treatment. In lupus nephritis section, indexes in animal tissues and serum were identified using specific kits, while pathological alterations in the mice kidney were examined through H&E staining. Additionally, qPCR was employed to determine the expression related to TGF-β 1 in kidney, thereby providing further insight into the silver nanoparticles mechanism. The findings indicated that silver nanoparticles reduced the mRNA expression levels of TGF-β 1 and NF-κB in the kidneys, while simultaneously increasing the Mn-SOD and IκB-α expression. Histological examination of H&E-stained sections revealed that silver nanoparticles mitigated the morphological abnormalities of the glomeruli and the inflammatory infiltration associated with nephritis. Silver nanoparticles demonstrated an inhibitory effect on the dsDNA positive rate in animal suffering from nephritis. Silver nanoparticles were found to reduce the increase in urinary protein and the pro-inflammatory cytokines concentrations in both the kidney and serum. In the periodontal model study, 0-3 ligatures were applied to induce the inflammatory periodontitis in right mandibular first molar neck in rats. The levels of inflammatory cytokines (IL1-β, CINC-1, IL-10 and TNF-α) were determined by common immunological test, ELISA. The findings revealed that Ag NPs administration could decease the IL1-β and TNF-α production in the rat periodontal model gum tissue. In addition, the outcome of this research indicated that IL1-β and TNF-α levels raised in the rat periodontal model gum tissue compared to control group. Ag NPs increased the levels of superoxide dismutase, catalase, and plasma bone alkaline phosphatase and reduced the IL1-β, TNF-α, inducible nitric oxide synthase and RANK genes mRNA expression. The results indicate that pre/post-treatment with Ag NPs because of its direct activity on pro-inflammatory cytokines inhibition improved the inflammatory symptoms in the periodontitis and lupus nephritis animals.

Schistosoma heamatobium tetraspanins TSP-2 and TSP-6 induce Dendritic Cells maturation, cytokine production and T helper cells differentiation in vitro

Urogenital schistosomiasis caused by Schistosoma haematobium is a major cause of disability in endemic areas. Despite its socio-economic burden, no vaccine exists and the parasite's immunobiology remains underexplored. Genome annotation has revealed over 40 different genes encoding tetraspanins, transmembrane proteins with known immunomodulatory properties in other plathelminthes. This study investigated the role of Sh-TSP-2, Sh-TSP-6 and Sh-TSP-23, which are expressed in the parasite's tegument and extracellular vesicles (EVs). Immature dendritic cells (DCs) from unexposed healthy donors were stimulated with these proteins to evaluate maturation maker expression and cytokine production. Also, pre-activated T CD4+ cells were stimulated with the DCs supernatant to assess cytokine gene expression. Sh-TSP-2 and Sh-TSP-6 induced maturation markers and cytokine production in DCs: Sh-TSP-2 increased CD80 and CD83 levels and the concentration of both pro-inflammatory (IL-6, TNF) and regulatory (IL-10) cytokines, while Sh-TSP-6 increased the production of IL-6. Moreover, supernatants from Sh-TSP-2 stimulated DCs induced the expression of Th1 (IFNɣ) and regulatory (IL-10) cytokines in CD4+ T cells, while Sh-TSP-6 induced Th2 (IL-4, IL-13) cytokine expression. These results provide evidence that S. haematobium tetraspanins modulate the response of human DCs and CD4+ T cells in vitro, and support Sh-TSP-2 as a promising vaccine candidate.

Investigation of Antioxidant and Anti-inflammatory Properties of Berberine Nanomicelles: In vitro and In vivo Studies.

In the present study, neuroprotective effects of berberine (BBR) and berberine nanomicelle (BBR-NM) against lipopolysaccharides (LPS)-induced stress oxidative were investigated, and compared by evaluating their antioxidant and anti-inflammatory activities in PC12 cells, and rat brains. A fast, green, and simple synthesis method was used to prepare BBR-NMs. The prepared BBR-NMs were then characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vitro experiments were carried out on the LPS-treated PC12 cell lines to investigate the anti-cytotoxic and antioxidant properties of BBR-NM and BBR. The results showed that BBR-NMs with a diameter of ~100 nm had higher protective effects against ROS production and cytotoxicity induced by LPS in PC12 cells in comparison with free BBR. Moreover, in vivo experiments indicated that the activity levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), increased in the brain of LPS-treated rats administrated with BBR-NM at the optimum dose of 100 mg.kg-1. BBR-NM administration also resulted in decreased concentration of lipid peroxidation (MDA) and pro-inflammatory cytokines, such as Serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Overall, BBR-NM demonstrated higher neuroprotective effects than free BBR, making it a promising treatment for improving many diseases caused by oxidative stress and inflammation.

Skeletal myocyte-specific knockout of Ptpn1 and Ptpn2 enhances inflammatory response in muscle and increases mortality in polymicrobial sepsis

Abstract Background Critically ill patients often suffer from heart and skeletal muscle atrophy and failure (intensive care unit acquired weakness; ICUAW). Inflammation and sepsis are major risk factors for ICUAW. Critically ill patients with sepsis frequently develop insulin resistance that decreases protein synthesis and increases protein degradation in muscle eventually leading to ICUAW. The link between inflammation and insulin resistance is not well understood, but protein tyrosine phosphatases (PTP), that inhibit insulin signaling via insulin receptor (INSR) dephosphorylation as well as inflammation-associated pathways, are implicated. Hypothesis: We hypothesized that PTP1B and TC-PTP mediate inflammation-induced insulin resistance and muscle atrophy in heart and skeletal muscle. Methods and Results qRT-PCR analyses showed that the proinflammatory cytokines tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6 caused a ~2-fold increase in Ptpn1/PTP1B and Ptpn2/TC-PTP mRNA expression in C2C12 myocytes as well as in neonatal rat ventricular cardiomyocytes. Inhibition of the IL-6/GP130 pathway by siRNA and inhibitors in myocytes in vitro and skeletal muscle specific gp130 knockout mice in vivo attenuated IL-6-induced Ptpn1/PTP1B and Ptpn2/TC-PTP mRNA expression. CLP-induced polymicrobial sepsis was associated with a significant increase in gene expression and protein content of pro-inflammatory cytokines (Tnf, Il1b, Ifng) and leukocyte markers (CD68, CD11c, F4/80) in muscle of skeletal myocyte specific double knockout (Ptpn1+Ptpn2loxP/loxP, MCK cre, dKO) compared to wildtype (Ptpn1+Ptpn2loxP/loxP) mice in sepsis. This also resulted in a lower survival rate of dKO mice in sepsis (42% WT vs. 23% dKO). Immunohistological analyses revealed centralized nuclei, macrophage/monocyte infiltration and enhanced regeneration (Myh3, Pax7, Ki67) in tibialis anterior muscle of septic dKO mice. A strong activation of the NLRP3-inflammasome, as indicated by cleavage of caspase 1, GSDMD, GSDME and caspase 8, indicative for a pronounced inflammation and activated cell death pathways was observed in muscle of septic dKO mice. Conclusion The proinflammatory cytokine IL-6 increases the expression of Ptpn1 and Ptpn2 and enhances overall PTP activity. Selective inhibition of the IL-6R/GP130 signaling pathway by JAK2- and STAT3-inhibition as well as Gp130 deletion in myocytes in vivo attenuates those effects. Muscle-specific deletion of Ptpn1 and Ptpn2 in skeletal muscle leads to increased mortality, enhanced pro-inflammatory response and induced inflammatory, programmed cell death pathways in sepsis. Our data show that Ptpn1 and Ptpn2 play a key anti-inflammatory role in skeletal muscle.