Serum Levels Of Proinflammatory Cytokines Research Articles

Establishment of a chronic biliary disease mouse model with cholecystoduodenal anastomosis for intestinal microbiome preservation.

Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver. Therefore, we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases. To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases. We established a mouse biliary disease model by directly connecting the gallbladder and duodenum, enabling ascending infection into the biliary tract without traversing the sphincter of Oddi. In the cholecystoduodenal anastomosis mouse model, we observed impaired epithelial structure, wall thickening, and macrophage recruitment in the gallbladder. Despite the absence of postoperative antibiotics, we detected no changes in serum proinflammatory cytokine levels, indicating no systemic inflammation. Moreover, patency between the gallbladder and duodenum was confirmed via common bile duct ligation. Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection, which significantly increased proinflammatory cytokine mRNA expression in the liver, duodenum, and ileum. These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum, leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans. The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.

Co-administration of Ayurvedic medicines Arshogrit and Jatyadi Ghrit, attenuate croton oil-induced hemorrhoids in rat model of recto-anal inflammation by modulating TNF-α and IL-1β levels

Objective To study the efficacy of co-administration of Arshogrit (AG) and Jatyadi Ghrit (JG), two herb-based Ayurvedic medicines, in rat model of croton oil-induced hemorrhoids. Significance Hemorrhoids refer to a pathological condition affecting the recto-anal region causing pain, swelling, bleeding and protrusion. The available therapies for hemorrhoids are symptomatic or invasive but are expensive and associated with adverse effects. Hence, there exists a need for efficacious and safer pharmacotherapies. Methods Ultra high performance liquid chromatography detected nine phytocompounds in AG and seven in JG. Seven fatty acids were additionally identified in JG by Gas Chromatography-Mass Spectrometry analysis. The in-vivo efficacy of the co-administration of AG, which was administered orally at the doses of 20, 60 and 200 mg/kg/day and JG, which was topically applied (100 mg/animal/day) was evaluated in Wistar rats by inducing hemorrhoids development with the application of croton oil preparation (COP) in the recto-anal area. Prednisolone was employed as the standard drug and was administered orally at the dose of 1 mg/kg/day. Results AG and JG were able to attenuate the croton oil-induced macro and microscopic anomalies. Gross pathological observation demonstrated remarkable decrease in croton oil-induced swelling, hemorrhage and formation of pseudomembrane, with the escalating doses of AG. Microscopic observation revealed alleviation in the histopathological lesions (necrosis, inflammation, hemorrhage/congestion, degeneration and dilatation of blood vessels). AG and JG additionally reduced COP-induced increase in the serum levels of pro-inflammatory cytokines. Conclusion This study convincingly demonstrates that co-administration of AG and JG is a potential therapy against hemorrhoids, warranting further investigations.

Decursin protects against DSS-induced experimental colitis in mice by inhibiting the cGAS-STING signaling pathway.

While studies have shown that Angelica gigas Nakai (A. gigas) can alleviate ulcerative colitis in mice, the therapeutic role of its main active ingredient, decursin, is uncertain. Therefore, we aimed to investigate the protective effect and mechanism of decursin against inflammatory bowel disease (IBD) in vivo using mice. IBD was simulated via induction with 3% dextran sodium sulfate (DSS), with or without daily treatment with decursin (10 mg/kg or 20 mg/kg) or 5-amino salicylic acid (5-ASA; 100 mg/kg) for 14 days. Mice were weighed and monitored daily for disease activity index (DAI) scoring. Colon tissues were collected for histopathological staining analysis, and serum was collected for ELISA measurement of proinflammatory cytokines. Western blotting was employed to analyze colonic expression levels of the tight junction-related proteins ZO-1, Occludin, and Claudin 1, as well as cGAS-STING signaling pathway-associated proteins. The expression levels of major proteins were verified using immunohistochemistry and immunofluorescence. Compared with the control group, DSS-induced mice showed decreased body weight, increased DAI scores, shortening of the colon, disrupted colon tissue structure, increased serum levels of proinflammatory cytokines, increased expression of factors involved in activating the cGAS-STING signaling pathway, and reduced expression of ZO-1, Occludin, and Claudin 1. Under decursin treatment, the pathological state of IBD was less severe, proinflammatory factors were downregulated, and activation of the cGAS-STING signaling pathway was inhibited. Our findings indicate that decursin helps restore the intestinal mucosal barrier and prevents activation of the cGAS-STING signaling cascade, alleviating experimental IBD in mice.

Milk fat globule membrane attenuates acute Salmonella typhimurium infection induced mouse model of colitis and ameliorates intestinal immunity

Research investigating the effects of milk fat globule membranes (MFGM) on Salmonella typhimurium-induced colitis, intestinal barrier integrity, and gut-associated immune responses remains scarce. This study aimed to investigate the potential of dietary MFGM to alleviate S. typhimurium-induced colitis in mice. Male C57BL/6J mice were administered S. typhimurium to induce colitis and were then subjected to dietary interventions with either bovine MFGM (BMFGM) or goat MFGM (GMFGM). Both BMFGM and GMFGM mitigated S. typhimurium-induced colitis, as evidenced by increased body weight, decreased mRNA levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) in the colon, reduced intestinal permeability, and increased mRNA expression of tight junction-associated genes (Claudin-1 and ZO-1). Additionally, there was a reduction in the number of S. typhimurium in the mesenteric lymph nodes and an improvement in CD4 T cell activation status. Furthermore, liver and spleen injury was reduced, and serum levels of pro-inflammatory cytokines (IFN-γ, IL-1β, IL-4, IL-2, IL-6, and TNF-α) were decreased by both type of MFGM. Overall, BMFGM and GMFGM effectively alleviated S. typhimurium-induced colitis and associated hepatic and splenic injuries.

Diagnosis and hormonal treatment of cystic ovaries associated with uterine disorders in Egyptian buffaloes: ultrasonography, histopathological and serological investigations

Cystic ovarian disease (COD) with uterine abnormalities is a postpartum reproductive pathology in Egyptian buffaloes causing significant economic losses. In this study, we aimed to employ various diagnostic methods for detecting cystic ovarian disease (COD) in Egyptian buffaloes. tour study assessed the effectiveness of the GnRH/PGF2α protocol as a treatment strategy. Our goal was to determine if this protocol could effectively reduce economic losses associated with cystic ovarian disease and improve herd fertility in Egyptian buffaloes. Eighty Egyptian buffalo cows were included in this study. They were identified to have follicular cysts through rectal examination, which was confirmed by ultrasonography. These buffaloes were then divided into two main groups: the COD Control (untreated) (GA) (n = 40) and COD group (GB) (n = 40) treated with GnRH/PGF2α. According to our immunological studies, buffaloes in the COD-treated group (GB) exhibited significantly lower serum levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) compared to the control group. This observation was consistent with the decline in E2 levels and the increase in P4 levels (p < 0.01–0.001) observed in the treated animals compared to the untreated group. Furthermore, serum cortisol and glucose concentrations decreased in COD-treated buffaloes. Histopathological examination of ovaries and uterine tissue from slaughtered COD buffaloes has revealed significant structural alterations. These include the presence of ovarian cysts of varying sizes with vacuolar degeneration. Additionally, lymphoplasmacytic endometritis was observed in the uterine tissue of affected animals, featuring degeneration and desquamation of the endometrial lining accompanied by infiltration of mononuclear inflammatory cells. Severe and prolonged cases of COD, which did not respond to treatment, exhibited marked adverse pathological changes upon histopathological assessment of the genital tract. In conclusion, hormonal treatment with GnRH/PGF2α appears to be effective in treating COD-affected animals. The study provides valuable insights into the immunological, biochemical, and histopathological aspects of cystic ovaries associated with uterine disorders in Egyptian buffaloes, while also evaluating hormonal treatment for cystic ovarian disease as a means to minimize economic losses and improve herd fertility in this species.

Synthesis of cytokines during physiological pregnancy

The article is devoted to the study of the level of pro- and anti-inflammatory cytokines in women with a physiological pregnancy, which is of great importance in obstetrics. Studying the synthesis of cytokines makes it possible to identify disturbances in the course of pregnancy, which is of great practical importance. The authors conducted a study of the level of cytokines in women with physiological pregnancy. Purpose of the study: to study the serum concentration of pro-inflammatory (IL-1β, IL-6, TNFα, IFNγ) and anti-inflammatory (IL-4, IL-10) cytokines in the dynamics of physiological pregnancy. The level of serum cytokines was studied in 94 women with a physiologically progressing pregnancy, who were registered with advisory clinics No. 14, No. 26, and No. 28 in Bukhara. The age of pregnant women ranged from 21 to 37 years, averaging 26.3±1.5 years. When compiling groups by trimester of pregnancy, it was revealed that: 35 women were in the first trimester of pregnancy; in 31 – the second trimester; and in 28 women – the third trimester of pregnancy. The control group consisted of 30 practically healthy non-pregnant women who were comparable in age. The levels of cytokines 1β, IL-6, TNFα, IFNγ, IL-4, and IL-10 was determined in peripheral blood serum using a set of reagents produced by Cytokin LLC (St. Petersburg, Russia) using the ELISA method according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using Student’s t-test using the standard Windows 2000 statistical software package. An increase in the level of proinflammatory cytokines (IFNγ, TNFα) was detected in the early stages of gestation compared with data from healthy non-pregnant women, which persisted in the second half of pregnancy against the background of an increase in anti-inflammatory cytokines (IL-4, IL-10). In the third trimester of pregnancy, a further increase in the serum level of pro-inflammatory cytokines (IL-1β, TNFα, IFNγ) was observed. The results of the studies indicate that at the level of the cytokine network there are mechanisms of fetoprotection, the violation of which can be the cause of pregnancy pathology.

Gross saponins of Tribulus terrestris attenuate rheumatoid arthritis by promoting apoptosis of fibroblast-like synoviocytes and reducing inflammation by inhibiting MAPK signalling pathway.

Among the numerous treatment options for rheumatoid arthritis (RA), the promotion of synoviocyte apoptosis and inhibition of inflammation are considered the most effective. However, the potential pro-apoptotic effects of gross saponins of Tribulus terrestris (GSTT), which are natural saponins derived from the herb Tribulus terrestris L., on rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and their essential molecular mechanisms remain unclear. The aim of the present study was to investigate the influence of different concentrations of GSTT on RA-FLSs using various assays, including cell counting kit-8 (CCK-8), reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot analysis. These assessments were conducted to evaluate the cell viability, changes in the levels of inflammatory cytokines, apoptosis rates and alterations in protein expression related to this process. In vivo, arthritis clinical score, haematoxylin and eosin (HE) staining and ELISA were used to assess paw inflammation, histopathology and serum inflammatory cytokine changes. Our findings demonstrated that GSTT substantially promotes the apoptosis of RA-FLSs and reduces pro-inflammatory cytokine levels. GSTT also reduced the Bcl-2/Bax ratio and inhibited JNK and p38 phosphorylation. Furthermore, GSTT exhibits positive effects on RA by improving clinical scores, reducing synovial inflammatory infiltration and lowering serum pro-inflammatory cytokine levels. Therefore, by promoting the apoptosis of RA-FLSs and suppressing inflammation through the inhibition of the MAPK signalling pathway, GSTT is a promising therapeutic intervention for RA.

Preventive effect of imperatorin against doxorubicin-induced cardiotoxicity through suppression of NLRP3 inflammasome activation.

Cardiotoxicity is one of the major obstacles to anthracycline chemotherapy. Anthracycline cardiotoxicity is closely associated with inflammation. Imperatorin (IMP), a furocoumarin ingredient extracted from Angelica dahurica, might have potential activity in preventing anthracycline cardiotoxicity due to its anti-cancer, anti-inflammatory, anti-oxidant, cardioprotective properties. This study aims to reveal the effect of IMP on doxorubicin (DOX)-induced cardiotoxicity and its underlying mechanism. We established a rat model of DOX-induced cardiotoxicity by intraperitoneal injection with DOX (1.25mg/kg twice weekly for 6weeks), and found that both IMP (25mg/kg and 12.5mg/kg) and dexrazoxane 12.5mg/kg relieved DOX-induced reductions in heart weight, change in cardiac histopathology, and elevated serum levels of LDH, AST and CK-MB. Moreover, DOX upregulated mRNA levels of NLRP3, CASP1, GSDMD, ASC, IL-1β and IL-18, elevated protein expressions of NLRP3, ASC, GSDMD-FL, GSDMD-N, pro‑caspase‑1, caspase‑1 p20, pro‑IL‑1β and IL‑1β in heart tissues, as well as increased serum levels of pro-inflammatory cytokines including IL-1β and IL-18, however both of IMP and dexrazoxane suppressed these alterations. In addition, we carried out neonatal rat cardiomyocytes experiments to confirm the results of the in vivo study. Consistently, pretreatment with IMP 25µg/mL relieved DOX (1μg/mL)-induced cardiomyocytes injury, including decreased cell viability and reduced supernatant LDH. IMP inhibited DOX-induced activation of NLRP3 inflammasome in cardiomyocytes. In conclusion, IMP had a protective effect against DOX-induced cardiotoxicity via repressing the activation of NLRP3 inflammasome. These findings suggest that IMP may be a promising alternative or adjunctive drug for the prevention of anthracycline cardiotoxicity.

Interferon regulatory factor 7 alleviates the experimental colitis through enhancing IL-28A-mediated intestinal epithelial integrity

BackgroundThe incidence of inflammatory bowel disease (IBD) is on the rise in developing countries, and investigating the underlying mechanisms of IBD is essential for the development of targeted therapeutic interventions. Interferon regulatory factor 7 (IRF7) is known to exert pro-inflammatory effects in various autoimmune diseases, yet its precise role in the development of colitis remains unclear.MethodsWe analyzed the clinical significance of IRF7 in ulcerative colitis (UC) by searching RNA-Seq databases and collecting tissue samples from clinical UC patients. And, we performed dextran sodium sulfate (DSS)-induced colitis modeling using WT and Irf7−/− mice to explore the mechanism of IRF7 action on colitis.ResultsIn this study, we found that IRF7 expression is significantly reduced in patients with UC, and also demonstrated that Irf7−/− mice display heightened susceptibility to DSS-induced colitis, accompanied by elevated levels of colonic and serum pro-inflammatory cytokines, suggesting that IRF7 is able to inhibit colitis. This increased susceptibility is linked to compromised intestinal barrier integrity and impaired expression of key molecules, including Muc2, E-cadherin, β-catenin, Occludin, and Interleukin-28A (IL-28A), a member of type III interferon (IFN-III), but independent of the deficiency of classic type I interferon (IFN-I) and type II interferon (IFN-II). The stimulation of intestinal epithelial cells by recombinant IL-28A augments the expression of Muc2, E-cadherin, β-catenin, and Occludin. The recombinant IL-28A protein in mice counteracts the heightened susceptibility of Irf7−/− mice to colitis induced by DSS, while also elevating the expression of Muc2, E-cadherin, β-catenin, and Occludin, thereby promoting the integrity of the intestinal barrier.ConclusionThese findings underscore the pivotal role of IRF7 in preserving intestinal homeostasis and forestalling the onset of colitis.

Harnessing ZIKV NS2A RNA for alleviating acute hepatitis and cytokine release storm by targeting translation machinery.

Hyperactivated inflammatory responses induced by cytokine release syndrome are the primary causes of tissue damage and even death. The translation process is precisely regulated to control the production of proinflammatory cytokines. However, it is largely unknown whether targeting translation can effectively limit the hyperactivated inflammatory responses during acute hepatitis and graft-versus-host disease. By using in vitro translation and cellular overexpression systems, we have found that the nonstructural protein gene NS2A of Zika virus functions as RNA molecules to suppress the translation of both ectopic genes and endogenous proinflammatory cytokines. Mechanistically, results from RNA pulldown and co-immunoprecipitation assays have demonstrated that NS2A RNA interacts with the translation initiation factor eIF2α to disrupt the dynamic balance of the eIF2/eIF2B complex and translation initiation, which is the rate-limiting step of translation. In the acetaminophen-induced, lipopolysaccharide/D-galactosamine-induced, viral infection-induced acute hepatitis, and graft-versus-host disease mouse models, mice with myeloid cell-specific knock-in of NS2A show decreased levels of serum proinflammatory cytokines and reduced tissue damage. Zika virus NS2A dampens the production of proinflammatory cytokines and alleviates inflammatory injuries by interfering translation process as RNA molecules, which suggests that NS2A RNA is potentially used to treat numerous acute inflammatory diseases characterized by cytokine release syndrome.

The Effects of Single- or Mixed-Strain Fermentation of Red Bean Sourdough, with or without Wheat Bran, on Bread Making Performance and Its Potential Health Benefits in Mice Model.

The effects of single- (Lactobacillus fermentum) or mixed-strain (Lactobacillus fermentum, Kluyveromyces marxianus) fermentation of red bean with or without wheat bran on sourdough bread quality and nutritional aspects were investigated. The results showed that, compared to unfermented controls, the tannins, phytic acid, and trypsin inhibitor levels were significantly reduced, whereas the phytochemical (TPC, TFC, and gallic acid) and soluble dietary fiber were increased in sourdough. Meanwhile, more outstanding changes were obtained in sourdough following a mixed-strain than single-strain fermentation, which might be associated with its corresponding β-glucosidase, feruloyl esterase, and phytase activities. An increased specific volume, reduced crumb firmness, and greater sensory evaluation of bread was achieved after mixed-strain fermentation. Moreover, diets containing sourdough, especially those prepared with mixed-strain-fermented red bean with wheat bran, significantly decreased serum pro-inflammatory cytokines levels, and improved the lipid profile, HDL/LDL ratio, glucose tolerance, and insulin sensitivity of mice. Moreover, gut microbiota diversity increased towards beneficial genera (e.g., Bifidobacterium), accompanied with a greater increase in short-chain fatty acid production in mice fed on sourdough-based bread diets compared to their controls and white bread. In conclusion, mixed-strain fermentation's synergistic effect on high fiber-legume substrate improved the baking, sensory quality, and prebiotic effect of bread, leading to potential health benefits in mice.

High-concentration hydrogen inhalation mitigates sepsis-associated encephalopathy in mice by improving mitochondrial dynamics.

Sepsis-associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H2) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H2 on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics. A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H2 for 1 h at 1 and 6 h post-surgery, respectively. The 7-day survival rate was recorded. Cognitive function was assessed using the Y-maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC-1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy. Inhalation of 67% H2 improved the 7-day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H2 inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis-related factors (PGC-1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels. Inhalation of high concentration (67%) of H2 in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics.

Nuciferine inhibits TLR4/NF-κB/MAPK signaling axis and alleviates adjuvant-induced arthritis in rats

Rheumatoid arthritis is an inflammatory condition primarily affecting the joints. Nuciferine (NCF), a key bioactive aporphine alkaloid biosynthesized in lotus leaves, exhibits promising anti-inflammatory and antioxidant properties. In this study, we investigated whether NCF could alleviate inflammatory arthritis conditions in a complete Freund's adjuvant (CFA)-mediated arthritis model in rats. The arthritis model was established through intradermal injection of CFA (100 μL) in the sub-plantar region of the right hind paw. The arthritic animals were treated orally with NCF at 5 and 10 mg/kg and indomethacin (Indo) at 5 mg/kg body weight as reference control. NCF treatment remarkably alleviated inflammatory joint swelling and arthritic index. The radiological and histological analysis revealed evidence of the beneficial effects of NCF. NCF treatment decreased the content of pro-inflammatory cytokines (TNF-α and IL-1β) and myeloperoxidase (MPO) activity and restored the anti-inflammatory cytokine (IL-10) in the paw joints. The serum levels of pro-inflammatory cytokines were also markedly reduced in the NCF (10 mg/kg) treatment group. Moreover, the arthritis-induced inflammatory mediators, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the toll-like receptor (TLR)-4, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling proteins were substantially decreased in the NCF treatment groups. NCF treatment also restored the antioxidant defense enzymes and abrogated lipid peroxidation in the paw tissue. Our findings strongly suggest that NCF is a promising therapeutic molecule for rheumatoid arthritis, inspiring further research, and development in this area.

Systemic and cerebro-cardiac biomarkers following traumatic brain injury: an interim analysis of randomized controlled clinical trial of early administration of beta blockers

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal.

UV-spectrophotometric and spectroscopic observed Vachellia nilotica and Nigella sativa formulations regularized the histopathological and biochemical parameters during wound contraction.

Diabetes mellitus causes impaired diabetic wounds which is linked to a number of pathological alterations that impede the healing of wounds. In the current research, Swiss albino mice were given alloxan monohydrate to induce diabetes and excision wounds of approximately 6 mm using biopsy punch. The diabetic wounds were treated with various biomaterials including Vachellia nilotica extract (VN), Nigella sativa extract (NS), V. nilotica nanoparticles (VNNPs) and N. sativa nanoparticles (NSNPs). Their effects were determined by evaluating the percent wound contraction, healing time, and histopathological analysis. The serum level of various biochemical parameters that is, pro-inflammatory cytokines, Matrix metalloproteinases (MMPs) and tissue inhibitor matrix metalloproteinases (TIMPs) were also determined. VNNPs group provided the best outcomes, with wound contraction 100% on 12th day. According to histopathological examination, VNNPs group reduced inflammation and encouraged the formation of blood vessels, fibroblasts, and keratinocytes. VNNPs group significantly alleviated the serum level of pro-inflammatory cytokines that are, TNF-α (19.4 ± 1.5 pg/mL), IL-6 (13.8 ± 0.6 pg/mL), and IL-8 (24.8 ± 1.2 pg/mL) as compared with the diabetic mice. The serum level of MMP2 (248.2 ± 7.9 pg/mL), MMP7 (316 ± 5.2 pg/mL), and MMP9 (167.8 ± 12.1 pg/mL) in the same group VNNPs were also observed much less than the diabetic mice. The serum level of TIMPs (176.8 ± 2.9 pg/mL) in the VNNPs group was increased maximally with respect to diabetic mice. It is concluded that nanoparticles and biomaterials possess healing properties and have the ability to repair the chronic/diabetic wound. RESEARCH HIGHLIGHTS: UV-spectrophotometric and Fourier transform infrared spectroscopy observation for functional group analysis and possible linkage between conjugates Optimization of the histopathological and biochemical markers after application of the formulations Microscopic analysis of epithelial tissues for evaluation of healing mechanisms Speedy contraction of wounds as the alleviation of the inflammatory and necrotic factors.

Soymilk yogurt fermented using Pediococcus pentosaceus TOKAI 759m improves mice gut microbiota and reduces pro-inflammatory cytokine production.

This study aimed to determine the anti-inflammatory activities and bioactive compounds of soymilk yogurt prepared using Lactiplantibacillus plantarum TOKAI 17 or Pediococcus pentosaceus TOKAI 759m. Mice were divided into five groups: normal diet (ND), soymilk, soymilk yogurt using L. plantarum TOKAI 17 (SY 17) or P. pentosaceus TOKAI 759m (SY 759m), and 0.5×109 cells of each starter strain (BC 17 or BC759m). In the SY 759m group, the serum pro-inflammatory cytokine levels and the cytotoxicity of natural killer cells were attenuated compared to the ND group. In the cecum microbiota, the abundances of butyrate-producing bacteria increased in the SY 759m and BC 17 groups. Furthermore, SY 759m metabolites contained high levels of aglycone isoflavone, adenine and showed a significant decrease in CCL-2 and interleukin-6 production in lipopolysaccharide-induced macrophage. In conclusion, soymilk yogurt produced using P. pentosaceus TOKAI 759m modulates the gut microbiota and can potentially prevent pro-inflammatory cytokine production.

Graphene Oxide Nanosheets Toxicity in Mice Is Dependent on Protein Corona Composition and Host Immunity.

Two-dimension graphene oxide (GO) nanosheets with high and low serum protein binding profiles (high/low hard-bound protein corona/HChigh/low) are used in this study as model materials and screening tools to investigate the underlying roles of the protein corona on nanomaterial toxicities in vivo. We proposed that the in vivo biocompatibility/nanotoxicity of GO is protein corona-dependent and host immunity-dependent. The hypothesis was tested by injecting HChigh/low GO nanosheets in immunocompetent ICR/CD1 and immunodeficient NOD-scid II2rγnull mice and performed histopathological and hematological evaluation studies on days 1 and 14 post-injection. HClow GO induced more severe acute lung injury compared to HChigh GO in both immunocompetent and immunodeficient mice, with the effect being particularly pronounced in immunocompetent animals. Additionally, HClow GO caused more significant liver injury in both types of mice, with immunodeficient mice being more susceptible to its hepatotoxic effects. Moreover, administration of HClow GO resulted in increased hematological toxicity and elevated levels of serum pro-inflammatory cytokines in immunocompromised and immunocompetent mice, respectively. Correlation studies were conducted to explore the impact of distinct protein corona compositions on resulting toxicities in both immunocompetent and immunodeficient mice. This facilitated the identification of consistent patterns, aligning with those observed in vitro, thus indicating a robust in vitro-in vivo correlation. This research will advance our comprehension of how hard corona proteins interact with immune cells, leading to toxicity, and will facilitate the development of improved immune-modulating nanomaterials for therapeutic purposes.

Protective effect of 5,4'-dihydroxy-6,8-dimethoxy7-O-rhamnosylflavone from Indigofera aspalathoides Vahl on lipopolysaccharide-induced intestinal injury in mice.

Intestinal inflammation is one of the main health challenges affecting the quality of life of millions of people worldwide. Accumulating evidence introduces several flavonoids with multifaceted therapeutic properties in inflammatory diseases including intestinal inflammation. Herein, we examined potential anti-inflammatory properties of 5,4'-dihydroxy-6,8-dimethoxy7-O-rhamnosylflavone (DDR) flavone derived from Indigofera aspalathoides Vahl (I. aspalathoides Vahl) on lipopolysaccharide (LPS)-induced intestinal inflammation and injury in mice. Oral DDR treatment decreased serum levels of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β. It reduced oxidative stress through augmenting the activities of catalase (CAT) and superoxide dismutase (SOD) and reducing the level of malondialdehyde (MDA) in the duodenum and colon tissues. Moreover, DDR enhanced the activities of digestive enzymes including trypsin, pancreatic lipase, and amylase, and increased the production of short-chain fatty acids (SCFAs) by colon microbiota. Histopathological investigation of duodenum and colon revealed that DDR inhibited inflammatory infiltration and largely restored mucosal architecture and protected lining integrity. Importantly, DDR suppressed activation of nuclear factor-κB (NF-κB) signaling pathway through reduced expression of Toll-like receptor 4 (TLR4) and expression and phosphorylation of P65. The current study identified DDR as anti-inflammatory flavonoid capable of ameliorating LPS-induced intestinal inflammation through suppression of NF-κB signaling.

The toxic effects of Helicobacter pylori and benzo(a)pyrene in inducing atrophic gastritis and gut microbiota dysbiosis in Mongolian gerbils.

Food chemical and microbiological contamination are major global food safety issues. This study investigated the combined effects of the food-borne pathogen Helicobacter pylori (H. pylori) and the pollutant benzo(a)pyrene (Bap) on atrophic gastritis and gut microbiota in Mongolian gerbils. The results demonstrated that simultaneous administration of H. pylori and Bap caused more severe weight loss, DNA damage, and gastritis in Mongolian gerbils compared with those exposed to H. pylori or Bap alone. The combination also significantly increased the serum level of proinflammatory cytokines, including IL-1β (p < .05), IL-6 (p < .0001), and TNF-α (p < .05). Additionally, the H. pylori and Bap combination altered the composition of gut microbiota in Mongolian gerbils: the relative abundance of Lactobacillus and Ligilactobacillus at the genus level (p < .05) was significantly reduced while the relative abundance of Allobaculum and Erysipelotrichaceae enhanced (p < .0001, p < .05). Our study revealed that the synergy of H. pylori and Bap can boost the development of atrophic gastritis and lead to gut microbiota dysbiosis in Mongolian gerbils, which provides essential implications for preventing contaminated foods to sustain life and promote well-being.

Prevalence of main risk factors and cytokine profile in patients with acute coronary syndrome and different serum myostatin levels

Objective. To study the prevalence of the main risk factors and the value of proinflammatory cytokines in patients with acute coronary syndrome (ACS) depending on the determined level of serum myostatin. Materials and methods. 120 patients with ST elevation ACS (STE-ACS) and non-ST-segment elevation ACS (NSTE-ACS), hospitalized in the cardiology department of the regional vascular center were examined. In 86 patients, the level of serum myostatin and proinflammatory cytokines was determined on the 5th day of the development of acute coronary syndrome. Results. Patients were divided into two subgroups depending on the level of serum myostatin which was determined: group 1 – with a lower level of myostatin, group 2 – with a higher level of myostatin. Group 1 (serum myostatin level from 0.038 to 0.084 ng/ml) consisted of 23 patients (16 males). Group 2 (serum myostatin level from 0.137 to 0.630 ng/ml) contained 21 patients (14 males). The main risk factors for cardiovascular diseases such as family history of early development of cardiovascular diseases, smoking, dyslipidemia, obesity, arterial hypertension and type 2 diabetes mellitus were assessed. The levels of pro-inflammatory cytokines were determined. Tumor necrosis factor alpha (TNF-alpha) and interleukin 18 (IL-18) levels were significantly higher in patients with higher myostatin levels. Correlation analysis revealed a relationship between serum myostatin concentration and TNF-alpha level (r = 0.34; p = 0.0016). Conclusions. No differences in the prevalence of risk factors in patients with ACS and different myostatin levels, except for smoking were revealed in the study, the frequency of smoking was higher in the group with higher myostatin levels. Greater activity of pro-inflammatory cytokines TNF-alpha and IL-18 was revealed in patients with higher levels of myostatin, as well as a significant correlation between the level of myostatin and TNF-alpha.