Serum Levels Of Proinflammatory Cytokines Research Articles

Huangqi Baihe Granules alleviate hypobaric hypoxia-induced acute lung injury in rats by suppressing oxidative stress and the TLR4/NF-κB/NLRP3 inflammatory pathway

Ethnopharmacological relevanceHuangqi Baihe Granules (HQBHG) are a modified formulation based on the traditional recipe “Huangqi Baihe porridge” and the Dunhuang medical prescription “Cistanche Cistanche Soup.” The Herbal medicine moistens the lungs and tones the kidneys in addition to replenishing Qi and feeding Yin, making it an ideal choice for enhancing adaptability to high-altitude hypoxic environments. Aim of the studyThe purpose of this study was to examine a potential molecular mechanism for the treatment and prevention of hypoxic acute lung injury (ALI) in rats using Huangqi Baihe Granules. Materials and methodsThe HCP-III laboratory animal low-pressure simulation chamber was utilized to simulate high-altitude environmental exposure and establish an ALI model in rats. The severity of lung damage was evaluated using a battery of tests that included spirometry, a wet/dry lung ratio, H&E staining, and transmission electron microscopy. Using immunofluorescence, the amount of reactive oxygen species (ROS) in lung tissue was determined. Superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) levels in lung tissue were determined using this kit. Serum levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta), and antiinflammatory cytokines like interleukin-10 (IL-10) were measured using an enzyme-linked immunosorbent assay kit. Gene expression changes in lung tissue were identified using transcriptomics, and the relative expression of proteins and mRNA involved in the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB p65)/Nod-like receptor protein 3 (NLRP3) pathway were determined using western blotting and quantitative real-time PCR. ResultsHQBHG was shown to enhance lung function considerably, decrease the wet/dry ratio of the lungs, attenuate lung tissue damage, suppress ROS and MDA formation, and increase SOD activity and GSH expression. The research also demonstrated that HQBHG inhibited the activation of the TLR4/NF-κB p65/NLPR3 signaling pathway in lung tissue, reducing the release of downstream pro-inflammatory cytokines. ConclusionsHQBHG exhibits potential therapeutic effects against ALI induced by altitude hypoxia through suppressing oxidative stress and inflammatory response. This suggests it may be a novel drug for treating and preventing ALI.

Peripheral blood regulatory B and T cells are decreased in patients with focal epilepsy

Patients with focal epilepsy of unknown cause (FEoUC) may display T cell infiltration in post-surgery brain specimens and increased serum levels of pro-inflammatory cytokines produced by B and T cells, indicating potential involvement of adaptive immunity. Our study aimed to investigate the peripheral blood distribution of B and T cell subgroups to find clues supporting the distinct organization of adaptive immunity in FEoUC. Twenty-two patients with FEoUC and 25 age and sex matched healthy individuals were included. Peripheral blood mononuclear cells were immunophenotyped by flow cytometry. Expression levels of anti-inflammatory cytokines and FOXP3 were measured by real-time PCR. Carboxyfluorescein succinimidyl ester (CFSE) proliferation assay was conducted using CD4+ T cells. Patients with FEoUC showed significantly decreased regulatory B (Breg), B1a, plasmablast and regulatory T (Treg) cell percentages, and increased switched memory B and Th17 cell ratios. Moreover, CD4+CD25+CD49d− Tregs of FEoUC patients displayed significantly reduced TGFB1 and FOXP3, but increased IL10 gene expression levels. CD4+ helper T cells of patients with FEoUC gave more exaggerated proliferation responses to phytohemagglutinin, anti-CD3 and anti-CD28 stimulation. Patients with FEoUC display increased effector lymphocyte, decreased regulatory lymphocyte ratios, and impaired Treg function and enhanced lymphocyte proliferation capacity. Overall, this pro-inflammatory phenotype lends support to the involvement of adaptive immunity in FEoUC.

Changes in levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in the Serum of Preterm Delivery Pregnant Women Affected by Gingivitis

Background: Periodontal disease increases local and systemic inflammatory responses in pregnant women, which may lead to premature delivery. Objectives: To detect maternal serum levels of proinflammatory cytokine (Interleukine-6, Interleukin-8) with preterm delivery in pregnant women suffering from gingivitis. Cases and methods: In this case-control study, a total of 85 pregnant women, were included in the study, of whom 55 had gingivitis: 25 preterm deliveries and 30 full-term deliveries. Thirty healthy pregnant women with healthy gingiva were in the control group. They were selected from Al-Ramadi Teaching Hospital for Gynecology and Pediatrics, from November 2022 to May 2023. Blood samples were collected from all participants and the biomarkers cytokines were detected by immunosorbent assay ( ) kits. Results: The current study showed an increased level of interleukin-6 and interleukin-8 in the pre-term delivery gingivitis group followed by full-term-delivery pregnant groups having gingivitis compared with the control group, with statistically highly significant differences ( ). Conclusion: Pregnant women with gingivitis with the highest levels of Interlukine-6 and Interlukine-8 were more prone to have premature delivery than those with lower levels of Interleukins and those without gingivitis. Received: June, 2023 Accepted: Aug, 2023 Published: Jan..2024

Targeting the tumor microenvironment to improve clinical outcomes in triple negative breast cancer patients and bridge the current disparity gap.

Triple negative breast cancer (TNBC) is a heterogenous disease that disproportionately affects Black women. TNBC outcomes among Black women are dismal secondary to multiple factors, such as poor healthcare accessibility resulting in delays in diagnosis, and aggressive disease biology in addition to a pro-tumor immune microenvironment (TME). Black women with breast cancer exhibit elevated levels of serum pro-inflammatory cytokines, and a pro-tumorigenic TME with higher immunosuppressive regulatory T cells (Tregs), M2 macrophages and exhausted CD8+ T cells. We have shown that the combined use of toll-like receptor 3 (TLR3) ligands with interferon-α (chemokine modulation: CKM) is able to enrich the tumor with CD8+ T cells, while not increasing immunosuppressive cells. Recent clinical trials have revealed the efficacy of immune checkpoint inhibitors (ICI) in rejuvenizing exhausted CD8+ T cells. We hypothesize that strategies to modulate the TME by enriching chemokines that attract CD8+T cells followed by reversal of CD8+ T cell exhaustion (ICI), when added to standard treatment, could potentially improve clinical outcomes, and mitigate the racial disparities in TNBC outcomes between Black and White Women.

Administering Lactiplantibacillus fermentum F6 decreases intestinal Akkermansia muciniphila in a dextran sulfate sodium-induced rat colitis model.

Probiotics are increasingly used to manage gut dysbiosis-related conditions due to their robust ability to manipulate the gut microbial community. However, few studies have reported that probiotics can specifically modulate individual gut microbes. This study demonstrated that administering the probiotic, Lactiplantibacillus fermentum F6, could ameliorate dextran sulfate sodium-induced colitis in a rat model, evidenced by the decreases in the disease activity index score, histopathology grading, and serum pro-inflammatory cytokine levels, as well as the increase in the serum anti-inflammatory cytokine levels. Shotgun metagenomics revealed that the fecal metagenomic of colitis rats receiving the probiotic intervention contained substantially fewer Akkermansia muciniphila than the dextran sulfate sodium group. Thus, the probiotic mechanism might be exerted by reducing specific gut microbial species associated with disease pathogenesis. A new paradigm for designing probiotics that manage diseases through direct and precise manipulation of gut microbes has been provided through this study.

Analysis of the liver-gut axis including metabolomics and intestinal flora to determine the protective effects of kiwifruit seed oil on CCl4-induced acute liver injury.

The hepatoprotective effects of kiwifruit seed oil (KSO) were evaluated on acute liver injury (ALI) induced by carbon tetrachloride (CCl4) in vivo. Network pharmacology was used to predict active compounds and targets. Metabolomics and gut microbiota analyses were used to discover the activity mechanism of KSO. KSO improved the liver histological structure, significantly reduced serum proinflammatory cytokine levels, and increased liver antioxidant capacity. The metabolomics analysis showed that KSO may have hepatoprotective effects by controlling metabolites through its participation in signaling pathways like tryptophan metabolism, glycolysis/gluconeogenesis, galactose metabolism, and bile secretion. The gut microbiota analysis demonstrated that KSO improved the composition and quantity of the gut flora. Network pharmacological investigations demonstrated that KSO operated by altering Ptgs2, Nos2, Ppara, Pparg and Serpine1 mRNA levels. All evidence shows that KSO has a hepatoprotective effect, and the mechanism is connected to the regulation of metabolic disorders and intestinal flora.

Molecular Approach to Identify Anti-inflammatory Potential of Stevioside in HFD-induced Type 2 Diabetic Rats: Evidence From in Vivo Study

Stevioside is a natural sweetener derived from the leaves of the Stevia rebaudiana plant. It has gained popularity as a sugar substitute due to its intense sweetness without adding calories or affecting blood sugar levels, making it a suitable option for people with diabetes or those looking to reduce their sugar intake. Studies have shown that stevioside has glucose lowering effects. Previous studies have shown that it has significant role in skeletal muscle but its role on expression of inflammatory signaling molecules in adipose tissue against high diet and sucrose-induced type-2 diabetes in experimental rats is yet to be done. The current research was undertaken to investigate if stevioside could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of stevioside (20 mg/kg b.wt) was administered orally for 45 days to high fat diet and sucrose induced type-2 diabetic rats. Interestingly, stevioside treatment restores the elevated serum levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) in adipocytes of diabetic rats. The gene expression of IR, GLUT4 and PPAR-γ mRNA were also significantly activated in stevioside treated groups but reduced IL-1 beta, IlL-6, IKKB, TNF-alpha and NFkB mRNA expression in diabetic adipose tissue. More importantly, stevioside acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that stevioside inhibits obesity induced insulin resistance by ameliorating the inflammatory events and upregulating insulin signalling molecules. Keywords: Stevioside, HFD-T2DM, pro inflammation, insulin signalling; adipose tissue, obesity; signaling pathways; Therapautics.

Glutamine attenuates bisphenol A-induced intestinal inflammation by regulating gut microbiota and TLR4-p38/MAPK-NF-κB pathway in piglets

Bisphenol A (BPA), as a kind of widely exerted environmental hazardous material, brings toxicity to both humans and animals. This study aimed to investigate the role of glutamine (Gln) in intestinal inflammation and microbiota in BPA-challenged piglets. Thirty-two piglets were randomly divided into four groups according to 2 factors including BPA (0 vs. 0.1%) and Gln (0 vs. 1%) supplemented in basal diet for a 42-day feeding experiment. The results showed BPA exposure impaired piglet growth, induced intestinal inflammation and disturbed microbiota balance. However, dietary Gln supplementation improved the growth performance, while decreasing serum pro-inflammatory cytokine levels in BPA-challenged piglets. In addition, Gln attenuated intestinal mucosal damage and inflammation by normalizing the activation of toll-like receptor 4 (TLR4)-p38/MAPK-nuclear factor-kappa B (NF-κB) pathway caused by BPA. Moreover, dietary Gln supplementation decreased the abundance of Actinobacteriota and Proteobacteria, and attenuated the decreased abundance of Roseburia, Prevotella, Romboutsia and Phascolarctobacterium and the content of short-chain fatty acids in cecum contents caused by BPA exposure. Moreover, there exerted potential relevance between the gut microbiota and pro-inflammatory cytokines and cecal short-chain fatty acids. In conclusion, Gln is critical nutrition for attenuating BPA-induced intestinal inflammation, which is partially mediated by regulating microbial balance and suppressing the TLR4/p38 MAPK/NF-κB signaling.

Treatment with β-Adrenoceptor Agonist Isoproterenol Reduces Non-parenchymal Cell Responses in LPS/D-GalN-Induced Liver Injury

There is an increasing evidence indicating the involvement of the sympathetic nervous system (SNS) in liver disease development. To achieve an extensive comprehension of the obscure process by which the SNS alleviates inflammatory damage in non-parenchymal liver cells (NPCs) during acute liver failure (ALF), we employ isoproterenol (ISO), a beta-adrenoceptor agonist, to mimic SNS signaling. ISO was administered to C57BL/6J mice to establish an acute liver failure (ALF) model using LPS/D-GalN, which was defined as ISO + ALF. Non-parenchymal cells (NPCs) were isolated from liver tissues and digested for tandem mass tag (TMT) labeled proteomics to identify differentially expressed proteins (DEPs). The administration of ISO resulted in a decreased serum levels of pro-inflammatory cytokines, e.g., TNF-α, IL-1β, and IL-6 in ALF mice, which alleviated liver damage. By using TMT analysis, it was possible to identify 1587 differentially expressed proteins (DEPs) in isolated NPCs. Notably, over 60% of the DEPs in the ISO + ALF vs. ALF comparison were shared in the Con vs. ALF comparison. According to enrichment analysis, the DEPs influenced by ISO in ALF mice were linked to biological functions of heme and fatty acid metabolism, interferon gamma response, TNFA signaling pathway, and mitochondrial oxidation function. Protein-protein interaction network analysis indicated Mapk14 and Caspase3 may serve as potentially valuable indicators of ISO intervention. In addition, the markers on activated macrophages, such as Mapk14, Casp1, Casp8, and Mrc1, were identified downregulated after ISO initiation. ISO treatment increased the abundance of anti-inflammatory markers in mouse macrophages, as evidenced by the immunohistochemistry (IHC) slides showing an increase in Arg + staining and a reduction in iNOS + staining. Furthermore, pretreatment with ISO also resulted in a reduction of LPS-stimulated inflammation signaling markers, Mapk14 and NF-κB, in human THP-1 cells. Prior treatment with ISO may have the potential to modify the biological functions of NPCs and could serve as an innovative pharmacotherapy for delaying the pathogenesis and progression of ALF.

SSRIs in the course of COVID-19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. Aretrospective study.

Relationships between inflammation and mood have been observed in terms of pro-inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant-induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID-19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro-inflammatory cytokine serum levels. The medical records of COVID-19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL-6) after admission for over a period of 22months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed. The entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n=107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL-6 levels in the treated group were significantly lower (p<0.01) than the levels in the untreated group, in every comparison. Outcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID-19, possibly mediated by IL-6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed.

Association between Proinflammatory Cytokines and Lung Cancer Risk: A Case-Cohort Study from a Community-Based Prospective Cohort

Recent studies have shed light on alterations to the proinflammatory tumor microenvironment as a significant carcinogenic mechanism. Despite previous studies on associations between proinflammatory cytokines and lung cancer risk, few studies have been conducted in Asian populations. This study aimed to investigate associations between proinflammatory cytokines and lung cancer risk, considering histological types, in the Korean general population. We carried out a case-cohort study on the Korean National Cancer Center Community (KNCCC) cohort (lung cancer cases: 136, subcohort: 822). Pre-diagnostic serum levels of proinflammatory cytokines (i.e., IL-6, TNF-α, IL-1β, IFN-γ, and IL-10) were measured using Quantikine® ELISA. A Cox proportional-hazards regression analysis was conducted. In this study, serum levels of IL-6, IL-1β, and IFN-γ were associated with lung cancer risk. IL-6 was associated with lung cancer, regardless of the histological type. IL-1β had an association only with adenocarcinoma, while IFN-γ had an association only with squamous-cell carcinoma. This study shows associations between serum levels of IL-6, IL-1β, and IFN-γ and lung cancer risk, underscoring the potential of these cytokines to act as risk biomarkers. The utilization of these biomarkers for risk prediction may hold the promise of facilitating the identification of the high-risk population.

Assessment of some cytokines levels in a pauci-immune crescentic glomerulonephritis patients

Background: Glomerulonephritis is the common cause of end-stage of renal failure. Rapidly progressive glomerulonephritis (RPGN) is characterized by glomerular injuries and formation of crescents. Moreover, anti-neutrophil cytoplasmic antibodies (ANCA), and pro-inflammatory cytokines play a damaging role in a crescent glomerulonephritis. Objectives: The main goal of the current study was aimed to determine the ANCA autoantibodies, and the serum levels of pro-inflammatory cytokines (IL-6, IL-17, IL-18, INF-γ), as well as the relationship between these cytokines and ANCA test in a pauci-immune crescentic glomerulonephritis patients. Methodology: The study was carried out in AL-Yarmouk teaching hospital and AL-Sader teaching hospital during the period from April 2022 to April 2023. This study was involved 90 patients with a crescentic glomerulonephritis disease, the diagnosis was made by the consultant medical staff. In addition to a 60 samples of healthy individuals as control group was involved to comparison the results. ANCA test was made by Indirect immunofluorescence method for the detection of ANCA autoantibodies in serum, in addition to measure the serum level of cytokines including IL6, IL-17, IL-18, and IFN-γ by using Enzyme Linked Immune Sorbent Assay methods. Results: This study has shown that the majority of patients were male (66.7%). Moreover, the most effected age groups within the age ≥ 61 years in percentage (65.5%) followed by the age group 51-60 years old (28.8%). There were 59 (65.5%) positive cases for ANCA from total patients and all of these cases were MPO-ANCA. The total RPGN patients were showed a highly significant increased mean serum levels of IL-18, IL-17, IL-6, and INF-γ as compared to healthy controls, as well as, the same cytokines were showed significant increased levels in myeloperoxidase (MPO)-ANCA positive serum in crescent glomerulonephritis patients as compared to ANCA –negative serum of patients. These results indicate a functional role of IL-6, IL-17, IL-18, and INF-γ in ANCA-mediated neutrophil activation by the interdependence of IL-6, IL-17, IL-18, and INF-γ priming for ANCA responses. Conclusion: It can be drawn from the present study that, the pro-inflammatory cytokines play an integral role in determining the course of disease and it can be used as major drug targets for therapy, as well as these cytokines have the ability to priming neutrophils thus contribute in the progression of a pauci-immune crescentic glomerulonephritis disease.

Anti-inflammatory effect of a novel millet gliadin peptide on mice with colitis

A novel peptide (VSAAAA) was obtained after the isolation, purification, and identification of millet gliadin. In order to explore the anti-inflammatory effect of peptide VSAAAA in vivo, the peptide VSAAAA was administered in the first three weeks, and ulcerative colitis was induced in mice with DSS aqueous solution in the last week. Results showed that the disease activity index and histopathological changes in the colon were significantly reduced after VSAAAAA intervention. The expression levels of serum proinflammatory cytokines in mice were significantly reduced. In addition, VSAAAA gavage significantly alleviated decrease in the expression levels of the intestinal nexus proteins ZO-1 and occludin and increase in the expression levels of p65 and p-p65 proteins in the NF-κB signaling pathway. Moreover, the intestinal flora composition of colitis mice was regulated by decreasing the relative abundance of harmful bacteria (Firmicutes) and increasing the relative abundant of beneficial bacteria (Bacteroides).

Patients with Chronic Coronary Syndrome Can Benefit from Consumption of Enriched Chicken Eggs: The Effects on Microvascular Function, Inflammatory Biomarkers, and Oxidative Status—Randomized Clinical Study

The aim of this clinical study was to determine the impact of the consumption of chicken eggs enriched with n-3 polyunsaturated fatty acids, selenium, vitamin E, and lutein on micro- and macrovascular endothelium-dependent dilation, inflammation biomarkers, and oxidative stress levels in participants with chronic coronary syndrome (CCS). This was a double-blind, placebo-controlled clinical study that included 30 CCS participants (9 women, 21 men) randomized into the control group (N = 15), who ate ordinary chicken eggs (three per day), and the Nutri4 group (N = 15), who ate enriched eggs (three per day) for 21 days. Microvascular and macrovascular endothelium-dependent vasodilation was evaluated by measuring forearm skin post-occlusive reactive hyperemia (PORH) and acetylcholine-induced dilation (AChID) and the flow-mediated dilation (FMD) of the brachial artery, respectively. The serum lipid profile, anti- and proinflammatory cytokine levels, serum concentration of nitric oxide synthase (NOS) isoforms, and oxidative stress biomarkers were measured before and after the diet protocols. Enriched, but not regular, chicken eggs significantly improved microvascular PORH and AChID and macrovascular FMD, increased the serum concentration of inducible NOS, decreased serum triglyceride levels, and decreased proinflammatory cytokine IL-17A and TGF-1β levels compared to initial measurements. Patients with CCS can benefit from the consumption of enriched chicken eggs due to improved lipid biomarkers, a more favorable anti-inflammatory milieu, and improved vascular relaxation at micro- and macrovascular levels.

Chronic alcohol and nicotine consumption as catalyst for systemic inflammatory storm and bone destruction in apical periodontitis.

To assess the periapical alveolar bone pattern and the serum levels of proinflammatory cytokines, biochemical markers and metabolites in rats subjected to chronic alcohol and nicotine consumption and induced apical periodontitis. Twenty-eight male Wistar rats were divided into four groups: Control, Alcohol, Nicotine and Alcohol+Nicotine. The alcohol groups were exposed to self-administration of a 25% alcohol solution, while the other groups were given only filtered water. The nicotine groups received daily intraperitoneal injections of a nicotine solution (0.19 μL of nicotine/mL), whereas the other groups received saline solution. Periapical lesions were induced by exposing the pulps of the left mandibular first molars for 28 days. After euthanasia, the mandibles were removed and the percentage bone volume, bone mineral density, trabecular thickness, trabecular separation and trabecular number of the periapical bone were measured using micro-computed tomography images. Serum samples were collected for analysis of proinflammatory cytokines (IL-1β, IL-4, IL-6 and TNF-α), biochemical and metabolomic analysis. Statistical analysis was performed with a significance level of 5%. Nonparametric data were analysed using the Kruskal-Wallis test followed by Dunn's test, while one-way anova followed by Tukey's test was performed for parametric data. The groups exposed to alcohol or nicotine consumption exhibited an altered bone pattern indicating lower bone density and higher levels of IL-1β, IL-6 and TNF-α compared to the Control group (p < .05). Significant differences were observed among the groups in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, triglycerides, urea, creatinine, albumin, uric acid, bilirubin and calcium. Metabolomic analysis revealed significant differences in glycine, phosphocholine, lysine, lactate, valine, pyruvate and lipids (CH2 CH2 CO), n(CH2 ) and n(CH3 ). Most of these parameters were even more altered in the simultaneous consumption of both substances compared to single consumption. Alcohol and nicotine chronic consumption altered several metabolic markers, impaired liver and kidney function, increased the production of systemic proinflammatory mediators and harmed the periapical bone microarchitecture in the presence of apical periodontitis. The simultaneous consumption of alcohol and nicotine intensified these detrimental effects.

In-situ complexation of rice starch and nobiletin by extrusion alleviates ulcerative colitis and modulates dysbiosis of intestinal flora in C57BL/6 mice

In this study, a rice starch–nobiletin (NOB) complex with well digestion-resistance by in-situ extrusion was chosen as a supplementary diet to protect against ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice. After oral administration, the complex alleviated colon damage caused by DSS, decreased serum levels of proinflammatory cytokines and colon oxidative stress, and improved the expression of tight junction proteins. Meanwhile, the complex may modify the gut microbiota by increasing its diversity and promoting potentially beneficial bacteria, as well as boosting short-chain fatty acid levels. Correlation analysis further revealed that proinflammatory cytokines and other injury factors were negatively related to Firmicutes and Verrucomicrobiota (phylum level), as well as Lactobacillus and Akkermansia (genus level). Overall, our results show that the rice starch–NOB complex protects intestinal barrier dysfunction in UC and may be a healthy addition to rice starch diets.

Potential effects of spirulina and date palm pollens on zinc oxide nanoparticles -induced hepatoxicity, oxidative stress, and inflammation in male albino rats.

The application of Zinc oxide nanoparticles (ZnO NPs) is substantially growing in industrial products. Therefore, humans are increasingly exposed to ZnO NPs daily due to their extensive range of applications, raising worries about their possible toxicity. In this study, the ameliorative effects of raw Phoenix dactylifera L. (date palm) pollens (DPP) and Spirulina platensis (SP) independently against ZnO NPS-induced hepatoxicity in male albino rats were examined. Six groups (6/group) of adult male albino rats received oral treatment using distilled water (control), SP (1000 mg/kg b. wt.), DPP (100 mg/kg b. wt.), ZnO NPs (100 mg/kg b. wt.), ZnO NPs +SP, and ZnO NPs + DPP respectively for 15 days. The results of the biochemical investigation indicated that the administration of ZnO NPs substantially upregulated (p < 0.05) transaminases, alkaline phosphatase, and bilirubin serum levels. Malondialdehyde and pro-inflammatory cytokine serum levels were also elevated after ZnO NPs administration. Simultaneously, the downregulated catalase and glutathione peroxidase serum activities were significantly suppressed in ZnO NPs treated rats. Moreover, exposure to ZnO NPs induced liver histopathological alterations. The administration of SP and DPP ameliorated the aforementioned effects caused by ZnO NPs. This result can be attributable to the downregulation of hepatic transaminases, alkaline phosphatase, and bilirubin in the serum and the antioxidation system's equilibration, thus alleviating the accumulation of reactive oxygen species. SP and DPP are natural antioxidants with the potential to eliminate inflammation as well as oxidative damage caused by ZnO NPs in hepatic tissue.

Association Between Biofilm Formation by U.P.E.C. and Serum Level of Several Cytokines

One hundred and eighty-nine subjects from Baghdad enrolled in this study (110 female and 79 male) and gathered into two investigated groups; the first group consisted of 149 patients, and the second group consisted of 40 healthy individuals. Results revealed after clinical laboratory diagnosis of urine samples 12 (8.1%) gave a negative bacterial culture, 137 (91.9%) were positive culture, while all urine samples of healthy control were negative. Gram staining and microscopic examination of bacterial colonies showed that 11(8.03%) out of 137 isolates were identified as Gram-positive and 126 (91.97%) as Gram-negative. After biochemical analysis and diagnosis by the Vitik system, the data demonstrated that a single infectious agent caused all U.T.I. cases. U.P.E.C. represented the most common bacterial agent because of several virulence factors responsible for its pathogenicity. The test tube method and Congo red agar medium have been used to detect biofilm formation. Results demonstrate that 129 (94.16 %) of bacterial isolates were producers, while just 8 (5.84 %) were non-producers. The results of the microtiter plate method revealed that the isolates were categorized into four groups: Strong, moderate, weak, and harmful. 22 (63.5%) were strong biofilm producers, 28 (20.449%) were moderate producers, 14 (10.22%) were weak producers, and 8 (5.84%) were unable to form biofilm. Serum levels of IL-1β, IL-6 and IL-8 were estimated by Sandwich ELISA, which were significantly higher in patients with different types of U.T.I.s than the healthy group. This study concluded that the U.P.E.C. represented the most common prevalent agent of U.T.I.s and more efficient biofilm-producer bacteria. The test tube method is the best qualitative, quick, and easy detection method of biofilm formation, while the microtiter plate is the best quantitative and sensitive method. A positive correlation was found between biofilm formation and elevated serum levels of proinflammatory cytokines, proportionally increased with advanced and severe, especially in old persons. Keywords: UTIs; ELISA; IL-1β; IL-6; IL-8; Iraq

Untargeted and Targeted Metabolomics Reveal the Active Peptide of Eupolyphaga sinensis Walker against Hyperlipidemia by Modulating Imbalance in Amino Acid Metabolism.

The active peptide (APE) of Eupolyphaga sinensis Walker, which is prepared by bioenzymatic digestion, has significant antihyperlipidemic effects in vivo, but its mechanism of action on hyperlipidemia is not clear. Recent studies on amino acid metabolism suggested a possible link between it and hyperlipidemia. In this study, we first characterized the composition of APE using various methods. Then, the therapeutic effects of APE on hyperlipidemic rats were evaluated, including lipid levels, the inflammatory response, and oxidative stress. Finally, the metabolism-regulating mechanisms of APE on hyperlipidemic rats were analyzed using untargeted and targeted metabolomic approaches. The results showed that APE significantly reduced the accumulation of fat, oxidative stress levels, and serum pro-inflammatory cytokine levels. Untargeted metabolomic analysis showed that the mechanism of the hypolipidemic effect of APE was mainly related to tryptophan metabolism, phenylalanine metabolism, arginine biosynthesis, and purine metabolism. Amino-acid-targeted metabolomic analysis showed that significant differences in the levels of eight amino acids occurred after APE treatment. Among them, the expression of tryptophan, alanine, glutamate, threonine, valine, and phenylalanine was upregulated, and that of arginine and proline was downregulated in APE-treated rats. In addition, APE significantly downregulated the mRNA expression of SREBP-1, SREBP-2, and HMGCR. Taking these points together, we hypothesize that APE ameliorates hyperlipidemia by modulating amino acid metabolism in the metabolome of the serum and feces, mediating the SREBP/HMGCR signaling pathway, and reducing oxidative stress and inflammation levels.

Neuroinflammation is linked to dementia risk in Parkinson's disease.

The development of dementia is a devastating aspect of Parkinson's disease (PD), affecting nearly half of patients within 10 years post-diagnosis. For effective therapies to prevent and slow progression to PD dementia (PDD), the key mechanisms that determine why some people with PD develop early dementia, while others remain cognitively unaffected, need to be understood. Neuroinflammation and tau protein accumulation have been demonstrated in post-mortem PD brains, and in many other neurodegenerative disorders leading to dementia. However, whether these processes mediate dementia risk early on in the PD disease course is not established. To this end, we used PET neuroimaging with 11C-PK11195 to index neuroinflammation and 18F-AV-1451 for misfolded tau in early PD patients, stratified according to dementia risk in our 'Neuroinflammation and Tau Accumulation in Parkinson's Disease Dementia' (NET-PDD) study. The NET-PDD study longitudinally assesses newly-diagnosed PD patients in two subgroups at low and high dementia risk (stratified based on pentagon copying, semantic fluency, MAPT genotype), with comparison to age- and sex-matched controls. Non-displaceable binding potential (BPND) in 43 brain regions (Hammers' parcellation) was compared between groups (pairwise t-tests), and associations between BPND of the tracers tested (linear-mixed-effect models). We hypothesized that people with higher dementia risk have greater inflammation and/or tau accumulation in advance of significant cognitive decline. We found significantly elevated neuroinflammation (11C-PK11195 BPND) in multiple subcortical and restricted cortical regions in the high dementia risk group compared with controls, while in the low-risk group this was limited to two cortical areas. The high dementia risk group also showed significantly greater neuroinflammation than the low-risk group concentrated on subcortical and basal ganglia regions. Neuroinflammation in most of these regions was associated with worse cognitive performance (Addenbrooke's Cognitive Examination-III score). Overall neuroinflammation burden also correlated with serum levels of pro-inflammatory cytokines. In contrast, increases in 18F-AV-1451 (tau) BPND in PD versus controls were restricted to subcortical regions where off-target binding is typically seen, with no relationship to cognition found. Whole-brain 18F-AV-1451 burden correlated with serum phosphorylated tau181 levels. Although there was minimal regional tau accumulation in PD, regional neuroinflammation and tau burden correlated in PD participants, with the strongest association in the high dementia risk group, suggesting possible co-localization of these pathologies. In conclusion, our findings suggest that significant regional neuroinflammation in early PD might underpin higher risk for PDD development, indicating neuroinflammation as a putative early modifiable aetiopathological disease factor to prevent or slow dementia development using immunomodulatory strategies.