IL-6 Activity Research Articles

Association of -607C/A (rs1946518) and -137G/C (rs187238) polymorphisms and immune response in radiation-exposed workers

Purpose Interleukin-18, transforming growth factor-β, and superoxide dismutase are important cytokines and antioxidants in protecting the body from damage caused by radiation exposure through an immune response mechanism. Genetic polymorphisms −607 C/A and −137 G/C are thought to affect the IL-18 cytokine in carrying out its function as a biomarker to indicate adverse conditions due to radiation. The purposes of this study were to investigate the association between 607 C/A and −137 G/C SNPs on the concentrations of IL-18, and to measure TGF-β and SOD activity in radiation workers and control group. Material and method We enrolled 40 radiation workers and 40 non-radiation workers as a control group. We determined genotype distribution of −607 C/A and −137 G/C SNPs and their correlation with IL-18 concentration by using PCR-RFLP method. We also measured the IL-18, TGF-β concentration, and SOD activity by using Elisa assay. Results and conclusion No relationship was found between −607 C/A and −137 G/C on IL-18 concentrations in all genotype groups, and no significant difference in IL-18 and TGF-β concentrations in the radiation worker and control groups. Significant differences were found only in lower SOD activity in radiation workers compared to controls. The −607 C/A and −137 G/C did not significantly correlate with IL-18 cytokine production in all genotypes. There was no significant difference between IL-18 and TGF-β concentrations in the radiation worker and control groups. However, there was a very significant decrease in the SOD activity of the radiation workers by 3.31 times compared to the controls.

Live Akkermansia muciniphila boosts dendritic cell retinoic acid synthesis to modulate IL-22 activity and mitigate colitis in mice

BackgroundThe interplay between gut microbiota and immune responses is crucial in ulcerative colitis (UC). Though Akkermansia muciniphila (Akk) shows therapeutic potential, the mechanisms remain unclear. This study sought to investigate differences in therapeutic efficacy among different forms or strains of Akk and elucidate the underlying mechanisms.ResultsEmploying a dextran sulfate sodium (DSS)-induced colitis mouse model, we assessed Akk’s impact on colitis using cellular cytokine analysis, immune phenotyping, proteomics, and biochemical methods. Our results suggest that treatment with live Akk effectively reduced colitis in the DSS-induced model, whereas heat-inactivated Akk did not yield the same results. Notably, Akk exhibited protective properties by promoting the secretion of IL-22 by Group 3 innate lymphoid cells (ILC3s), as evidenced by the absence of protection in IL-22 knockout mice. Additionally, Akk augmented the population of CD103+CD11b− dendritic cells (DCs) and enhanced their retinoic acid (RA) synthesis through the modulation of RALDH2, a crucial enzyme in RA metabolism. The depletion of RALDH2 in DCs diminished Akk’s protective properties and impaired IL-22-mediated mucosal healing. Mechanistically, Akk activated RA production in DCs by enhancing the JAK2-STAT3 signaling pathway. Additionally, various strains of Akk may exhibit differing abilities to alleviate colitis, with the novel strain Am06 derived from breast milk showing consistent efficacy similar to the reference strain.ConclusionsIn summary, our findings indicate that certain strains of Akk may mitigate colitis through the promotion of RA synthesis and IL-22 secretion, underscoring the potential efficacy of Akk as a therapeutic intervention for the management of UC.6tGY-f7LLTpAkqkC5_h35yVideo

Assessment of Interleukin 17 in Egyptian Systemic Lupus Erythematosus Patients as a Biomarker in Disease Activity.

Systemic lupus erythematosus (SLE) is a chronic idiopathic systemic autoimmune disorder with dysregulation of adaptive and innate immune systems. Interleukin (IL)-17 is the prototypical pro-inflammatory cytokine of T helper 17 (Th17) cells. Therefore, it contributes to the pathogenesis of human SLE. The aim of the research paper was the evaluation of IL-17 level as a biomarker in the SLE cohort and its relation to disease activity and analysis of IL-17 concentration in patients with lupus nephritis and non-lupus nephritis. The research enrolled 45 SLE patients according to Systemic Lupus International Collaborating Clinics Classification Criteria (SLICC), and age and sex-matched. The patients underwent full history, clinical examination, laboratory investigation, and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) calculation. The mean age ± SD of the participants equaled 32 ± 11 years, and serum IL-17 in SLE cases was statistically significantly high (p < 0.001). No statistically significant correlations were reported between disease activity according to SLEDAI and IL-17. In addition, a statistically significant positive correlation was reported between IL-17 and ESR, and a high statistically significant negative correlation was reported between IL-17 and C3 and C4 (P < 0.001). A statistically significant positive correlation was reported between IL-17 and 24-hour urinary proteins with a Pvalue of 0.01. SLE cases demonstrated higher levels of serum IL-17, contributing to SLE pathogenesis. However, no statistically significant difference was reported between IL-17 and Lupus nephritis. IL-17 and SLE activity (SLEDAI) did not correlate. A statistically significant positive relation was reported between IL-17 and 24-hour urinary proteins. Additionally, a high statistically significant negative correlation was reported between IL-17 and C3 and C4.

Single nucleotide polymorphisms: impact on susceptibility to chemotherapy in patients with colorectal cancer.

Single-nucleotide polymorphisms (SNPs) in enzyme-coding genes play a role in susceptibility to anti-cancer therapy. A prospective study was performed of the relationship between enzyme activity and treatment response, drug toxicity and hypersensitivity reactions in 51 patients with colorectal cancer treated with fluoropyrimidine-based chemotherapy. SNP analysis was performed in 22 enzyme-coding genes with a previously described role in treatment efficacy. SLC6 and MTHR enzyme activity was related with rates of progressive disease, GSTP1 activity with anti-EGFR antibodies-related skin toxicity, CYP3A5 and MTHR with chemotherapy dose reduction, CYP2B6, IL10, MTHR and TYMS activity with the risk of drug hypersensitivity reactions. Pharmacogenetics is a valuable predictive marker in oncology, related to chemotherapy treatment response, toxicity and hypersensitivity.

Neuroprotective role of curcumin on the hippocampus against the oxidative stress and inflammation of streptozotocin-induced diabetes in rats.

In recent years, it has gained importance to determine the effects of diabetes on central nervous system complications. This study aimed to assess the neuroprotective properties of curcumin against neuronal damage in the rat hippocampus caused by diabetes. In accordance with this purpose, we investigated the effects of curcumin on oxidative/antioxidative parameters and pro-inflammatory cytokines in the hippocampal tissue of diabetic Wistar rats. For this purpose, 32 adults, male and healthy Wistar Albino rats were used. Animals were randomly divided into four separate groups: control (C), curcumin(Cu), diabetes (D) and Diabetes + Curcumin (DCu)-treated groups. 60mg/kg STZ i.p. A single dose was administered to D and DCu groups. Cu and DCu groups were given 50mg/kg/day curcumin by gavage. After four weeks of treatment, the animals were decapitated under anesthesia and tissue samples were taken for analyses of the parameters (TNF-α, IL-6, IL-1, IL-10, MDA, SOD, catalase, and GSH activities) in the hippocampal tissue. TNF-α, IL-6, IL-1, and MDA levels were increased significantly (p < 0.05) in rats with diabetes compared to the other three groups. TNF-α, IL-6, IL-1, and MDA levels were lower in DCu group animals compared to the D group. It was determined that IL-10, SOD, Catalase, and GSH levels, which were significantly decreased in the D group, increased in the curcumin-supplemented diabetic group (DCu). The relevant sentence has been changed as follows. In conclusion, our findings from this study prove the protective effect of curcumin against diabetes-induced neuropathy in the hippocampus in rats with STZ-induced diabetes.

Selective PPARδ Agonist GW501516 Protects Against LPS-Induced Macrophage Inflammation and Acute Liver Failure in Mice via Suppressing Inflammatory Mediators.

Inflammation is critical in the development of acute liver failure (ALF). Peroxisome proliferator-activated receptor delta (PPARδ) regulates anti-inflammatory responses and is protective in several diseases such as obesity and cancer. However, the beneficial effects and underlying mechanisms of PPARδ agonist GW501516 in ALF remain unclear. This study investigated the molecular mechanisms underlying the anti-inflammatory effects of GW501516 in macrophages and assessed its protective potential against lipopolysaccharide (LPS)/galactosamine (GalN)-induced ALF. In vivo administration of GW501516 significantly reduced LPS/GalN-induced hepatotoxicity, as evidenced by lower mortality, decreased liver damage, and attenuated secretion of IL-1β, IL-6, and TNF-α. GW501516 treatment also decreased LPS-induced nitric oxide synthase 2 (NOS2) expression and nitric oxide (NO) production in RAW264.7 cells, an effect reversed by PPARδ siRNA. Additionally, GW501516 inhibited LPS-induced phosphorylation of p38 and c-Jun N-terminal kinase (JNK), suggesting that inactivation of these MAPKs contributes to its effects. The secretion of IL-6, TNF-α, and NF-κB DNA-binding activity were also suppressed by GW501516, while the nuclear translocation of the NF-κB p65 subunit was unaffected. In conclusion, our findings suggest that GW501516 exerts protective effects in ALF by inhibiting the production of inflammatory mediators. Therefore, GW501516 may act as a potential agent for developing anti-inflammatory therapies for ALF.

Rats Exposed to Excess Sucrose During a Critical Period Develop Inflammation and Express a Secretory Phenotype of Vascular Smooth Muscle Cells.

Neonatal rats that receive sucrose during a critical postnatal period (CP, days 12 to 28) develop hypertension by the time they reach adulthood. Inflammation might contribute to changes during this period and could be associated with variations in the vascular smooth muscle (VSMC) phenotype. We studied changes in inflammatory pathways that could underlie the expression of the secretory phenotype in the VSMC in the thoracic aorta of rats that received sucrose during CP. We analyzed histological changes in the aorta and the expression of the COX-2, TLR4, iNOS, eNOS, MMP-2 and -9, and β- and α-actin, the quantities of TNF-α, IL-6, and IL-1β using ELISA, and the levels of fatty acids using gas chromatography. The aortic wall presented disorganization, decellularization, and wavy elastic fibers and an increase in the lumen area. The α- and β-actin expressions were decreased, while COX-2, TLR4, TNF-α, and the activity of IL-6 were increased. Oleic acid was increased in CP in comparison to the control group. There is transient hypertension at the end of the CP that is accompanied by inflammation and a change in the phenotype of VSMC to the secretory phenotype. The inflammatory changes could act as epigenetic signals to determine the development of hypertension when animals reach adulthood.

Neoadjuvant Intratumoral Plasmid IL-12 Electro-Gene-Transfer and Nivolumab in Patients with Operable, Locoregionally Advanced Melanoma.

Intratumoral tavokinogene telseplasmid delivered by electroporation (TAVO-EP) results in localized expression of IL-12 within the tumor microenvironment (TME). This study evaluated neoadjuvant TAVO-EP combined with intravenous nivolumab followed by surgery and adjuvant nivolumab in patients with operable, locoregionally advanced melanoma. The neoadjuvant phase comprised up to 3 × 4-week cycles during which TAVO-EP was given intratumorally on days 1, 8, and 15 (optional) concurrently with 480 mg nivolumab intravenously on day 8 of each 4-week cycle. Surgery followed, and adjuvant nivolumab was initiated after surgery. The primary endpoint was pathologic complete response (pCR). Secondary endpoints included major pathologic response (MPR; pCR or near pCR). Sixteen patients were enrolled, and the preoperative radiological response rate was 63%. One patient declined surgery after experiencing a significant clinical response. Among the remaining 15 patients, the pCR rate was 60% and the MPR was 80%. No patient with MPR has had disease recurrence with a median follow-up from the date of surgery of 15.4 months. At baseline, most patients exhibited low CD8+ tumor-infiltrating lymphocytes, PD-L1, and IFN-γ gene expression signature. There was enhanced immune activation following treatment in the TME and blood, including increased immune-related gene expression, CD8+ tumor-infiltrating lymphocytes, and proliferating immune cell subsets. The clinical efficacy of neoadjuvant intratumoral TAVO-EP + nivolumab is promising with 80% of patients achieving an MPR. Evidence of potent immune activation both systemically and within the TME along with a favorable safety profile supports the activity of local IL-12 and anti-PD-1 based regimens.

Comparison of the activity of IL-6 and IL22 as more inflammatory cytokines related to the pathogenesis of celiac disease between active and gluten-free diet patient

This study aimed to investigate the activity of anti-inflammatory IL-6 (aIL-6) and pro-regenerative IL-22 in celiac disease patients based on their dietary habits. By comparing cytokine levels between patients on active gluten-containing diets and those on gluten-free diets, we sought to elucidate the potential role of diet in modulating inflammatory responses and clinical outcomes in celiac disease. The study made use of an enzyme-linked immunosorbent assay (ELISA) to evaluate the serum levels of interleukins IL6 and IL22. This was performed on three different groups: Group 1, which consisted of 40 recently identified active celiac patients; Group 2, which included 20 patients following a gluten-free diet; and Group 3, which contained 40 apparently healthy individuals .the individuals included in the study had been previously confirmed as celiac patients through serology, specifically by detecting both anti-IgA and IgG antibodies against tTG and gliadin using indirect immunofluorescence. The findings revealed a notable difference in IL6 levels between the patient and control groups, with a P-value of 0.041. However, when the patient groups were compared using the least significant difference (LSD) method, there were no significant differences between Group 1 (G1) and Group 2 (G2) with a P-value of 0.101, and between Group 1 and Group 3 (G3) with a P-value of 0.720. Yet, a more pronounced difference was observed between Group2 and Group3,with a P-value less than 0.015.Regarding IL22 levels, there was a significant difference between the patient and control groups, with a P-value of 0.002. Further comparisons using the LSD method revealed no significant differences between Group 1 and Group 2, with a P-value less than 0.154. However, a highly significant difference was found between Group 1 and Group 3, with a P-value less than 0.01. Also, significant differences were observed between Group 2 and Group 3, with a P-value less than 0.012. In conclusion, there is important role of the inflammatory cytokines il-6 and il-22 in the inflammation of celiac disease and potential role for these cytokines in the pathogenesis and management of the disease. Adherence to a gluten-free diet appears to have a beneficial effect on modulating the inflammatory response and improving clinical outcomes in celiac disease..

Comparison of the Activity of IL-6 and IL22 as More Inflammatory Cytokines Related to the Pathogenesis of celiac Disease Between Active and Gluten-Free Diet Patient

This study aimed to investigate the activity of anti-inflammatory IL-6 (aIL-6) and pro-regenerative IL-22 in celiac disease patients based on their dietary habits. By comparing cytokine levels between patients on active gluten-containing diets and those on gluten-free diets, we sought to elucidate the potential role of diet in modulating inflammatory responses and clinical outcomes in celiac disease. The study made use of an enzyme-linked immunosorbent assay (ELISA) to evaluate the serum levels of interleukins IL6 and IL22. This was performed on three different groups: Group 1, which consisted of 40 recently identified active celiac patients; Group 2, which included 20 patients following a gluten-free diet; and Group 3, which contained 40 apparently healthy individuals .the individuals included in the study had been previously confirmed as celiac patients through serology, specifically by detecting both anti-IgA and IgG antibodies against tTG and gliadin using indirect immunofluorescence. The findings revealed a notable difference in IL6 levels between the patient and control groups, with a P-value of 0.041. However, when the patient groups were compared using the least significant difference (LSD) method, there were no significant differences between Group 1 (G1) and Group 2 (G2) with a P-value of 0.101, and between Group 1 and Group 3 (G3) with a P-value of 0.720. Yet, a more pronounced difference was observed between Group2 and Group3,with a P-value less than 0.015.Regarding IL22 levels, there was a significant difference between the patient and control groups, with a P-value of 0.002. Further comparisons using the LSD method revealed no significant differences between Group 1 and Group 2, with a P-value less than 0.154. However, a highly significant difference was found between Group 1 and Group 3, with a P-value less than 0.01. Also, significant differences were observed between Group 2 and Group 3, with a P-value less than 0.012. In conclusion, there is important role of the inflammatory cytokines il-6 and il-22 in the inflammation of celiac disease and potential role for these cytokines in the pathogenesis and management of the disease. Adherence to a gluten-free diet appears to have a beneficial effect on modulating the inflammatory response and improving clinical outcomes in celiac disease.

Thymoquinone Abrogates Acrylamide-Induced Cerebellar Toxicity via Modulation of Nuclear Factor Erythroid 2-Related Factor 2/Nuclear Factor Kappa B Signaling, Oxidative Neuroinflammation, and Neuroapoptosis in Rats.

Acrylamide (ACR) is an obligate human neurotoxicant ubiquitously produced and found in foods processed at high temperature. There is an increasing public health concern regarding its probable carcinogenic potential. Its prevailing toxicity mechanism is oxidative inflammation and apoptosis. Herein, we explored whether thymoquinone (TQ), a bioactive quinone in Nigella sativa seed, could mitigate ACR-induced cerebellar toxicity in rats. Our study design featured four rat groups: control, TQ (5 mg/kg bw), ACR (50 mg/kg bw), and TQ + ACR (5 mg/kg + 50 mg/kg). After 14 days of respective treatments, cerebellar homogenate was used to estimate acetylcholinesterase activity (AchE) activity, antioxidant enzymes (catalase [CAT], superoxide dismutase [SOD], and glutathione peroxidase [GPx]), malondialdehyde (MDA), inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-4, and IL-10), nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), caspase-3, and caspase-9. The level of DNA damage by fragmentation and histopathological lesions was also determined in the cerebellum. The rat exposure to ACR caused significant decreases in the cerebellar activities of AchE, CAT, SOD, and GPx, IL-4, IL-10, and expression of Nrf2, whereas the levels of MDA, IL-6, TNF-α, caspase-3, and caspase-9 were prominently increased compared with the control. ACR induced significant DNA fragments and cerebellar lesions when compared with the control. Contrarily, TQ treatment inhibited the depression of CAT, SOD, and GPx activities and reversed the MDA level and expression of Nrf2/NF-κB, cytokines, and caspases. These effects were confirmed by reduced DNA damage and cerebellar histopathological lesions in comparison with the ACR. TQ afforded neuroprotection via its antioxidant, anti-inflammatory, and antiapoptotic mechanisms in rats.

Pharmacological assessment of delphinidin in counteracting polystyrene microplastic induced renal dysfunction in rats

Polystyrene microplastics (PSMP) are toxic environmental contaminants which can damage various body organs including kidneys. Delphinidin (DEL) is a potential anthocyanidin flavonoid with significant pharmacological benefits. This research was conducted to analyze the protective effect of DEL to avert PSMP prompted renal dysfunction. Rats (n = 24) were divided into 4 separate groups: Control, PSMP (0.01 mgkg−1), PSMP (0.01 mgkg−1) + DEL (25 mgkg−1) and only DEL (25 mgkg−1). Our results showed that PSMP exposure reduced the expressions of Nrf-2 and antioxidant genes while increasing the expression of Keap1. Besides, PSMP intoxication escalated the level of kidney injury markers (urea, KIM-1, creatinine and NGAL) while inducing substantial reduction in the levels of creatinine clearance. Moreover, PSMP significantly reduced the levels of GSH, GST, SOD, HO-1, CAT, GSR, GPx while escalating MDA and ROS. Conversely, inflammatory biomarkers including IL-1β, TNF-α, NF-kB, IL-6 and COX-2 activity were increased due to PSMP intoxication. Our results showed that PSMP administration increased the expressions of Bax and caspase-3 while decreasing the expression of Bcl-2. However, DEL treatment significantly restored the PSMP-induced renal impairments. Therefore, it is suggested that DEL could be used as a therapeutic compound to alleviate PSMP-induced kidney damage in rats, possibly due to its strong pharmacological properties.

FUNDC1 mediated mitochondria-dependent ferroptosis of epithelial cells in model of asthma by FBXL2/ar/GPX4 signaling pathway of SUMO1 at K136

This study aimed to explore the critical role of FUNDC1 on epithelial cells in model of asthma. Patients with asthma and normal healthy volunteers were obtained from our hospital. The serum of FUNDC1 mRNA expression was down-regulated in patients with asthma. Meanwhile, the serum of FUNDC1 mRNA expression was positive correlation with IgE and anti-HDM IgE protein. FUNDC1 expression in lung tissue of mice model was decreased in mice model of asthma. Sh-FUNDC1 enhanced asthma in mice model of asthma. FUNDC1 up-regulation reduced IL-4, IL-5, IL-10 and IL-13 activity levels in vitro model of asthma.FUNDC1 down-regulation promoted IL-4, IL-5, IL-10 and IL-13 activity levels in vitro model of asthma. FUNDC1 reduced ferroptosis of epithelial cells in model of asthma through the inhibition of mitochondrial damage. FUNDC1 induced FBXL2 and AR protein expression in model of asthma. FUNDC1 interlinked with FBXL2 is modified by SUMO1 at K136. FBXL2, ASN-205, GLN-204, ARG-235, and GLN-237 form hydrogen bonds with FUNDC1's ASP-15, ASP-16, GLU-25, and ARG-29, with lengths of 2.3, 3.1, 2.9, 2.3, and 2.9 Å, respectively. The induction of FBXL2 reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma. The inhibition of AR reduced the effects of Sh-FUNDC1 on asthma in mice model of asthma Overall, FUNDC1 prevents ferroptosis of airway epithelial cells of asthma through FBXL2/AR/GPX4 signaling pathway of SUMO1 at K136. FUNDC1 might benefit the treatment of asthma or other pulmonary disease.

Exploring the Influence of IL-8, IL-10, Patient-Reported Pain, and Physical Activity on Endometriosis Severity.

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain, and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis.

HIV-1 latency reversal and immune enhancing activity of IL-15 is not influenced by sex hormones.

The role of different biological variables including biological sex, age, and sex hormones in Human immunodeficiency virus (HIV) cure approaches is not well understood. The γc-cytokine IL-15 is a clinically relevant cytokine that promotes immune activation and mediates HIV reactivation from latency. In this work, we examined the interplay that biological sex, age, and sex hormones 17β-estradiol, progesterone, and testosterone may have on the biological activity of IL-15. We found that IL-15-mediated CD4+ T cell activation was higher in female donors than in male donors. This difference was abrogated at high 17β-estradiol concentration. Additionally, there was a positive correlation between age and both IL-15-mediated CD8+ T cell activation and IFN-γ production. In a primary cell model of latency, biological sex, age, or sex hormones did not influence the ability of IL-15 to reactivate latent HIV. Finally, 17β-estradiol did not consistently affect reactivation of translation-competent reservoirs in CD4+ T cells from people living with HIV who are antiretroviral therapy (ART) suppressed. Our study has found that biological sex and age, but not sex hormones, may influence some of the biological activities of IL-15. Understanding how different biological variables may affect HIV cure therapies will help us evaluate current and future clinical trials aimed toward HIV cure in diverse populations.

Synthetic thymic hexapeptide in the correction of alterations of antibacterial immune defense and normalization of the profile of proinflammatory cytokines in immunocompromized Children with local unlimited acute peritonitis

The study of dysregulatory disorders of the immune system underlying the immunopathogenesis of severe purulent-inflammatory diseases (PIDs) is important for development of new therapeutic tactics of restoring antibacterial defense. Acute peritonitis (AP) is a severe PID of the abdominal cavity, the course of which are dependent on the treatment, cytokine balance and adequate functioning of the immunity. Objective: to evaluate the modulating effects on the immune system and the levels of proinflammatory cytokines of the synthetic thymic hexapeptide, active substance of Imunofan, included in the complex postoperative treatment (CPOT) of immunocompromised children with local AP. Clinical and immunological examination of 20 immunocompromised children aged 5–12 years with local AP was carried out before (study group 1, SG1) and after (study group 1a, SG1a) CPOT including synthetic thymic hexapeptide (Arginyl-alpha-AspartylLysyl-Valyl-Tyrosyl-Arginine, НР), alongside 20 conditionally healthy children (comparison group, SG). The content of T and B lymphocytes, natural killer cells (NK), levels of serum pro-inflammatory cytokines IL-1β, IL-6, TNFα, IL-8, IL-18, phagocytic and microbicidal activity of neutrophils (NG) were assessed. In SG1, before treatment, a decrease in the number of T lymphocytes, T helpers, CTL-lymphocytes, NK and an increase in the level of B lymphocytes was revealed. Defects in the effector functions of NG were determined: impaired bacterial antigen killing and decreased NADPH oxidase activity. It was established that in case of AP in immunocompromised children, the cytokine profile is characterized by overproduction of studied proinflammatory and neutrophil-associated cytokines. After complex treatment including immunomodulatory therapy, there was a restoration of the content of T lymphocytes, T helper cells, TCTL lymphocytes, an increase in the number of NK and decrease in the level of B lymphocytes. In addition, regression of the levels of inflammatory, including neutrophil-associated, cytokines and emergence of effector functions of NG due to restoration of NADPH oxidases activity, was noted. Thus, the restoration of immunological parameters in AP leads to earlier regression of the purulent-inflammatory process in the abdominal cavity and to the absence of postoperative complications. The clinical and immunological effects of the immunomodulatory therapy program with inclusion of the drug based on HP determines the feasibility of its use in the postoperative period in immunocompromised children with local AP.

Activity and levels of TNF-α, IL-6 and IL-8 in saliva of children and young adults with dental caries: a systematic review and meta-analysis

BackgroundCytokines play an important role in the immunopathogenesis of dental caries. A systematic review and meta-analysis was carried out with the following three objectives: 1)To deepen and discuss through a comprehensive analysis of the literature the effects of dental caries on the activity and levels of TNF-α, IL-6 and IL-8 in saliva of children and young adults, 2)To compare the levels of this cytokines in saliva of the exposure group (moderate-severe dental caries) with the control group (caries-free or mild dental caries), and 3)To determine whether the levels of these cytokines could be used as a complementary clinical diagnostic tool to assess the severity of dental caries.MethodsThe protocol followed PRISMA and Cochrane guidelines and was registered in the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/MF74V. A digital search was performed in PubMed/MEDLINE, Cochrane, Scopus, and Google Schoolar databases from February 15th, 2012, to January 13th, 2024. The methodological validity of the selected studies was assessed using Joanna Briggs Institute (JBI) tool. A meta-analysis was performed using a random-effects model to evaluate the association between dental caries/health, and the concentration of TNF-α, IL-6 and IL-8.ResultsThe search strategy provided a total of 126 articles, of which 15 investigations met the inclusion criteria. The total number of patients studied was 1,148, of which 743 represented the case/exposure group, and 405 represented the control group. The age of the patients ranged from 3 to 25 years. IL-6 was the most prevalent cytokine in the saliva of children and young adults with active dental caries. The meta-analysis revealed that there are significant differences between the levels of IL-6 and TNF-α in saliva of children with active dental caries compared to their control groups.ConclusionsThe findings suggest that IL-6 and TNF-α levels may have potential as complementary biomarkers for assessing dental caries severity. However, further research is needed to validate these findings in larger and more diverse populations before clinical application.

Anxiolytic, Antidepression, and Memory-Enhancing Effects of the Novel Instant Soup RJ6601 in the Middle-Aged of Female Rats.

Due to the health benefits of polyphenols and dietary fiber in combating mental disorders, we hypothesized that a polyphenol- and dietary fiber-enriched soup (RJ6601) would improve mental wellness in a rat model of middle-aged women. To test this hypothesis, female Wistar rats aged 18 months (350-450 g) were orally administered RJ6601 at doses of 200 and 400 mg/kg BW for 28 days. The anxiolytic, antidepression, and memory-enhancing effects were assessed every 7 days throughout the study period. The neuron density and levels of activities of AChE, total MAO, MAO-A, MAO-B, MDA, SOD, CAT, GSH-Px, IL-1β, IL-6, and BDNF in the prefrontal cortex at the end of study were also investigated. Furthermore, the amounts of Lactobacillus spp. and Bifidobacterium spp. in their feces were also determined. The results revealed that the developed soup shows anxiolytic, antidepression, and memory-enhancing effects. An increased neuron density; reductions in AChE, total MAO, MAO-A, MAO-B, and MDA; and an elevation of serum BDNF, together with increased amounts of both bacterial species in feces, were also observed. Our results suggest that RJ6601 is a potential mental wellness promotion supplement that enhances BDNF levels, brain plasticity, neurotransmitter balance, and oxidative stress and inflammation status, along with improving microbiota.

UPLC-QTOF-MS characterized, herbal medicine, pancogrit modulates NF-κB and JAK2/STAT3 signaling pathways in cell-based model of TNF-α dependent acute pancreatitis

Acute pancreatitis develops as a local inflammatory condition of the pancreas due to a wide range of factors including overdose of alcohol or drugs, gall stones, etc. At present, medications based on herbal formulations have gained importance due to their better safety profile. Current study assessed the pharmacological effects of Pancogrit, an herbal medicine, in caerulein and TNF-α-induced in vitro pancreatitis models. A comprehensive evaluation of phytometabolites present in Pancogrit was conducted and 85 phytometabolites were identified through UPLC-QTOF-MS and UPLC-UV. The bioactivity and mode of action of Pancogrit were assessed in caerulein-induced AR42J (rat pancreatic acinar) cells, TNF-α-induced PANC-1 (human pancreatic duct) cells, and NF-κB reporter cells. Pancogrit was found to decrease the elevated amylase and lipase activity in caerulein-induced AR42J cells. It ameliorated the increased ROS levels, IL-6, IL-8 release and NF-κB activity in TNF-α-induced PANC-1 and NF-κB reporter cells. Pancogrit also downregulated IL-6, IL-1β, ICAM-1, and STAT3 gene expression in PANC-1 cells. Moreover, Pancogrit inhibited the protein expression levels of phosphorylated STAT3, phosphorylated and total JAK2 in TNF-α-induced PANC-1 cells. Taken together, Pancogrit is a clinically relevant therapeutic agent for mitigation of pancreatitis.

Differential Pharmacodynamic Effects on Psoriatic Biomarkers by Guselkumab Versus Secukinumab Correlate with Long-Term Efficacy: An ECLIPSE Substudy

IL-23 is a cytokine produced by myeloid cells that drives the T helper 17 pathway and plays an essential role in the pathophysiology of plaque psoriasis. IL-23 activation initiates a cascade of cytokines subsequently inducing the expression of many psoriasis-related proteins. This study aimed to better understand the underlying mechanisms driving the differences between IL-23 and IL-17A blockade in patients with psoriasis and their implications for durability of clinical responses. Serum and/or skin biopsies were isolated from patients treated with guselkumab or secukinumab for evaluation of potential biomarkers of pharmacodynamic response to treatment. Guselkumab treatment led to significantly greater reductions of IL-17F and IL-22 serum levels than treatment with secukinumab at weeks 24 and 48, demonstrating sustained regulation of the IL-23/T helper 17 pathway. Analyses of proteomic and transcriptomic profiles of patient sera and skin biopsies demonstrated differential regulation of proteins involved in chemokine, TNF, and relevant immune signaling pathways to a greater degree with guselkumab than with secukinumab treatment. These data provide insights into the differences between the mechanisms and impact of IL-23 and IL-17A blockade in psoriasis, with implications for efficacy observations and treatment paradigms. Trial Registration: The original study was registered at ClinicalTrials.gov (NCT03090100).