IL-6 Concentrations Research Articles

Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.

This study aims to identify biomarkers for treatment response of atezolizumab plus bevacizumab (Atezo+Bev) in patients with hepatocellular carcinoma (HCC). 96 patients who received Atezo+Bev or lenvatinib as a first-line systemic therapy were enrolled as the training group after propensity score matching (PSM), and 42 patients treated with Atezo+Bev were enrolled as the validation group. 17 serum cytokines were measured by Luminex multiplex assay at the start of treatment. For further assessment of the association between cytokine levels and the tumor microenvironment (TME), immunohistochemistry (IHC) was performed on pre-treatment liver biopsy specimens. In the derivation set, multivariate analysis identified elevated IL-6 as an independent risk factor in the Atezo+Bev group (HR 5.80: p<0.01), but not in the lenvatinib group; in a subset analysis of patients with low IL-6, PFS was longer in the Atezo+Bev training group than in the lenvatinib group (p = 0.02). A validation study also showed a significantly longer prognosis in the low IL-6 group for both PFS (p = 0.0001) and OS (p = 0.03). Serum IL-6 had a positive correlation with tumor IL-6 expression (ρ = 0.56, p < 0.0001) and an inverse correlation with the CD8/CD163-positive cell count ratio (ρ = -0.4, p < 0.01). Serum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.

Study the Relationship of IFN-γ (+874A/ T) Polymorphism, and Some Cytokines with Breast Cancer in a Population from Baghdad City, Iraq

Background: Breast cancer is still a complicated and common health issue that affects millions of people globally. Aim: the current investigation aimed to study the relationship of IFN-γ (+874 A/T) genetic polymorphism, and some cytokines to breast cancer women in a population from Baghdad city/ Iraq. Materials and Methods: In this study, (80) females with an age of (20-60) years were employed; they were attending Oncology Teaching Hospital, Medical City, Baghdad. All these females were notified regarding the purpose of these investigations and agreed to its protocol. 80 healthy women were taken into the current study for comparison purposes. Results: The findings demonstrated that C3 levels showed a significant (P≤0.05) elevation in patients compared to healthy females. C4 levels demonstrated significantly (P≤0.05) elevation in patients that compared to healthy females. IL-6 levels significantly (P &lt;0.05) increased in patients compared with control group (4.15±0.65 pg/ml). IL-17 concentration in serum of patients showed a significant (P &lt;0.05) increased in patients compared with healthy ones. T and A alleles of IFN-γ T / A +874 locus had distinct results when repeated distribution was used to compare women who had breast cancer to healthy individuals. In the patient BC sample, the T allele was 42.4%, while the allele T in the control group was 71.4%. While the allele A in the sample of BC patients, which is 57.6%, compared to the allele A in control group, which was 28.6%. Conclusions: This study suggests that elevated IL-6 and IL-17 levels, along with specific IFN-γ gene polymorphisms, could serve as potential biomarkers for breast cancer risk and prognosis.

Low-grade systemic inflammation, but not neuroinflammation, is associated with 12-month postoperative outcome after total hip arthroplasty in patients with painful osteoarthritis.

Better prediction of outcome after total hip arthroplasty (THA) is warranted. Systemic inflammation and central neuroinflammation are possibly involved in progression of osteoarthritis and pain. We explored whether inflammatory biomarkers in blood and cerebrospinal fluid (CSF) were associated with clinical outcome, and baseline pain or disability, 12 months after THA. A total of 50 patients from the Danish Pain Research Biobank (DANPAIN-Biobank) between January and June 2018 were included. Postoperative outcome was assessed as change in Oxford Hip Score (OHS) from baseline to 12 months after THA, pain was assessed on a numerical rating scale, and disability using the Pain Disability Index. Multiple regression models for each clinical outcome were included for biomarkers in blood and CSF, respectively, including age, sex, BMI, and Kellgren-Lawrence score. Change in OHS was associated with blood concentrations of tumour necrosis factor (TNF), interleukin-8 (IL-8), interleukin-6 receptor (IL-6R), glycoprotein 130 (gp130), and IL-1β (R2 = 0.28, p = 0.006), but not with CSF biomarkers. Baseline pain was associated with blood concentrations of lymphotoxin alpha (LTα), TNFR1, TNFR2, and IL-6R (R2 = 0.37, p < 0.001) and CSF concentrations of TNFR1, TNFR2, IL-6, IL-6R, and IL-1Ra (R2 = 0.40, p = 0.001). Baseline disability was associated with blood concentrations of TNF, LTα, IL-8, IL-6, and IL-1α (R2 = 0.53, p < 0.001) and CSF concentrations of gp130, TNF, and IL-1β (R2 = 0.26, p = 0.002). Thus, preoperative systemic low-grade inflammation predicted 12-month postoperative outcome after THA, and was associated with preoperative pain and disability. This study highlights the importance of systemic inflammation in osteoarthritis, and presents a possible path for better patient selection for THA in the future. Preoperative central neuroinflammation was associated with preoperative pain and disability, but not change in OHS after THA.

Enhanced Production of IL-10 in PCR-Positive Dogs Infected with E. canis and A. phagocytophilum Facilitate Specific Immune Responses

Infection of dogs with the tick-borne rickettsiae Ehrlichia and Anaplasma provokes an immune response mediating the pathology and bacterial resistance. IL-10 is the main anti-inflammatory cytokine and plays a multifaceted role in host protection. The study aimed to investigate circulating IL-10 in 32 dogs naturally infected with A. phagocytophilum and E. canis, identified by PCR positivity, and 33 PCR-negative animals which tested positive for antibodies against these pathogens, as well as 22 healthy animals. The highest quantity of IL-10, measured by ELISA, was observed among dogs positive simultaneously for anti-E. canis and anti-A. phagocytophilum IgG antibodies, followed by dogs positive for anti-E. canis only. The concentration of IL-10 in PCR-positive dogs was almost three and a half times higher than that measured in the control group (77.09 ± 23.61 pg./mL vs. 21.55 ± 4.61 pg./mL; p = 0.0015) and five times higher than the concentration of interleukin in PCR-negative animals (77.09 ± 23.61 pg./mL vs. 14.86 ± 3.01 pg./mL; p = 0.000016). The highest level of IL-10 was observed in PCR-positive dogs with mixed infection (120.54 ± 44.18), followed by the level in PCR-positive dogs for E. canis only (78.81 ± 16.92). The lowest level of IL-10 was observed in PCR-positive dogs for A. phagocytophilum only (56.32 ± 12.68). We may suggest that infection with E. canis and A. phagocytophilum stimulates the IL-10 production in dogs, which may facilitate specific antibody responses.

Nasal Mucus Cytokines Are Correlated with Spirometry Measures in CRS Patients with Comorbid Asthma.

CRS patients with asthma show differential nasal mucus cytokine signatures based on endotype. IL-7 concentration is positively associated with higher %FEV1 and %FVC in CRS patients with asthma.

Oxyresveratrol and/or Dapagliflozin Attenuate Doxorubicin-Induced Nephrotoxicity via Modulation of PPAR-γ/Nrf-2/HO-1, NF-κB/TNF-α/Keap-1, and Bcl-2/Caspase-3/ATG-5 signaling pathways in rats.

Among the most undesirable effects that lead to the restriction of doxorubicin (DOX) use in chemotherapy is kidney damage. This research aimed to assess the possible defenses against DOX-induced nephrotoxicity offered by oxyresveratrol (ORES) and/or dapagliflozin (DAPA). Five groups of eight male Swiss albino rats each were created from a total of sixty-four. One intravenous injection of DOX (10mg/kg) was given into the tail vein on the fourteenth day of the experiment; in the meantime, ORES (80mg/kg) and DAPA (10mg/kg) were given orally 14 days prior to the DOX injection and 2 days following the DOX injection. In rats given DOX, ORES and/or DAPA both successfully reduced the kidney weight, kidney/bodyweight ratio, and blood levels of creatinine, uric acid, and urea. They also increased final body weight and albumin serum levels. Additionally, lower serum concentrations of TNF-α and IL-6 were noted, along with a lower kidney content of caspase-3. Furthermore, the expression of the Bcl-2 gene was upregulated, as were the Nrf-2, PPAR-γ, and HO-1 proteins, and there was a downregulation of the ATG-5, Keap-1, and NF-κB renal gene expression. These findings support a decrease in oxidative stress and relief of histopathological alterations. The current study's findings suggest that ORES and/or DAPA pretreatment could be a viable therapeutic approach to ameliorate DOX-induced nephrotoxicity.

Основные противовоспалительные цитокины и интерлейкин 6 у больных ревматоидным артритом: взаимосвязи и клиническое значение

In the pathogenesis of rheumatoid arthritis (RA), an important role is played by dysfunction between the production of the main anti-inflammatory interleukins (IL) IL-4, IL-10 and proinflammatory (IL-6) cytokines. Objective. Determination of IL-4, IL-6 and IL-10 concentrations in RA patients with advanced stage of the disease, assessment of the relationship between them, clinical indices of disease activity, the presence of rheumatoid factor (RF) and antibodies to cyclic citrullinated peptide (CCP). Material and methods. The study included 154 RA patients (41 males and 113 females) of middle age (56.0 (50.0; 64.0) years), disease duration (9.4 (3.0; 13.0) years), seropositive 129 (83.8 %) for IgM RF and/or 106 (68.8 %) ACPP with moderate or high (DAS28-ESR – 5.40 (4.65; 6.00)) disease activity. The concentration of IL-4, IL-6, IL-10 in the blood serum was determined by multiplex technology. Results. In patients with RA, the concentration of IL-4 did not differ significantly from the control, and for IL-6 and IL-10 it was significantly higher than in donors. High values of IL-6 were significantly more common (51.6 %) than IL-4 (12.33 %, p = 0.001) and IL- 10 (16.23%, p = 0.001). Reliable correlations were found between the hyperproduction of IL-4 and IL-6, IL-6 and IL-4, IL-10. For IL-4 and IL-10, such an association was not found. The concentration and frequency of increased IL-4, IL-6, IL-10 did not differ in patients positive or negative for IgM RF. The concentration of IL-4 was significantly higher in the group of patients seronegative for ACPA compared to seropositive ones, and the prevalence of high IL-4 values was also noted in this group. No such association was found for IL-6 and IL-10. The concentration of IL-6 significantly positively correlated with the indices (DAS28-ESR, CDAI, SDAI) of clinical activity of RA, and the level of IL-4 was positively associated with CDAI, SDAI, IgM RF and inversely with ACPA values. The concentration of IL-10 was associated with CDAI, SDAI, IgM RF. Conclusion. In patients with RA in the advanced stage of the disease, the production of IL-6 predominates over the production of IL-4 and IL-10. In the presence of interrelations between these cytokines, there are certain differences in the associations with clinical indices and laboratory indicators of disease activity, IgM RF and ACPA.

The influence of light on Interleukin-10: A preliminary study

Light influences circadian rhythms, including that of the stress hormone cortisol. Cortisol, in turn, has been observed to promote expression of the anti-inflammatory cytokine IL-10. It is thus of interest whether the cytokine IL-10 is also influenced by light, perhaps in accord with the diurnal variations in cortisol. Hence, this highly standardized preliminary sleep laboratory study in healthy adult men investigated a potential influence of different light exposure on IL-10 and cortisol concentrations in blood. In a between-subject design, N = 42 participants were exposed to either bright, dim, blue or red light after wake-up. Two mixed-model analyses with the factors of light condition and time (across eight IL-10 and cortisol sampling points) were conducted. Additionally, area under the curve measurements (AUCg and AUCi) were calculated for both cortisol and IL-10. Across all conditions, IL-10 and cortisol concentrations significantly changed over time. However, none of the light conditions exerted a greater influence on IL-10 or cortisol levels than others. For cortisol, there was greater total output (AUCg) in the blue-light condition in particular. Further research is needed to gain insight into whether or not types of light or cortisol levels have a hand in influencing natural IL-10 concentrations.

The Role of Chitinase 3-Like-1 (YKL-40) and Proinflammatory Biomarkers in the Pathogenesis of Pediatric Tick-Borne Encephalitis in a Polish Cohort.

Chitinase 3-like-1 (CHI3L1), also known as YKL-40, is a potential biomarker for neuroinflammatory conditions. It is upregulated in Alzheimer's disease, multiple sclerosis, and traumatic brain injury. However, its involvement in pediatric tick-borne encephalitis (TBE) has not been addressed yet. This study aimed to evaluate CHI3L1 and its relationship with other inflammatory cytokines, blood-brain barrier (BBB) integrity, immune response, and disease severity in pediatric patients with TBE. A total of 22 pediatric TBE patients hospitalized in Bialystok, Poland were included in this study. Participants were categorized as having meningoencephalitis (n=6) or meningitis (n=16). The integrity of the brain-blood barrier (BBB) was assessed using the albumin quotient (albQ). Biomarker indices were calculated to account for variations in BBB permeability. The concentrations of CHI3L1, CCL2, chemerin, CXCL2, IFN-γ, IL-1-β, IL-4, IL-6, IL-13, and TNF-α in both serum and CSF, were measured using the Luminex Multiplex Assay od admission and two weeks later when symptoms resolved. CSF and serum concentrations of CHI3L1 did not differ between the encephalitis and meningitis cases. After adjusting for BBB permeability, the CHI3L1 index was 2.4-fold lower in patients with encephalitis than in those with meningitis (P=0.008). There was a post-treatment reduction of CHI3L1, IL-6, and TNF-α CSF concentrations. We also found and improvement in BBB permeability in younger children but in older albQ remained abnormal. Correlation analysis revealed associations between CHI3L1 levels and pro-inflammatory markers, notably chemerin, IL-6, and TNF-α, across both clinical groups. Our findings suggest that CHI3L1 CSF levels reflect the inflammatory activity in pediatric TBE and may help to differentiate between meningoencephalitis and meningitis. The observed interactions between CHI3L1 and other cytokines underscore its potential involvement in inflammatory response to the virus. The prolonged disruption in BBB integrity in older children might reflect age-dependent differences in the severity of TBE. These insights advance our understanding of TBE pathogenesis in children and support further investigation of CHI3L1 as a biomarker for TBE diagnosis and management.

Preparation of combined colchicine with loxoprofen sodium loaded in dissolvable microneedles and its anti-gouty arthritis effect

Both colchicine (Col) and loxoprofen sodium (LS) are first-line drugs for gouty arthritis (GA). Dissolvable microneedles (DMNs) represent an innovative transdermal drug delivery system (TDDS) that maximizes the therapeutic effect of drugs. In this paper, a novel TDDS of combined Col with LS loaded in DMNs (Col-LS-DMNS) was prepared to treat GA. To assess the synergistic effects of Col and LS, cell viability assays were conducted using monosodium urate (MSU)-induced HaCaT cells. The optimization of the Col-LS-DMNs formulation was carried out through sealing membrane puncture tests, single-factor experiments, and Box-Behnken response surface methodology. The quality of Col-LS-DMNs was assessed using high-performance liquid chromatography (HPLC), scanning electron microscopy (SEM), sealing membrane puncture tests, in vitro mouse skin puncture experiments, and Franz diffusion cell assays. The therapeutic effect of Col-LS DMNs on GA through animal experiments. Results demonstrated that Col and LS exhibit a synergistic effect, with optimal mass ratio of 1:1. The optimal formulation included PVP K30 and CMC Na at a mass ratio of 10:1, with 63% water content and a mixed dosage of Col and LS of 42 mg. The drug content in Col-LS-DMNs was (19.11±0.65) μg of Col and (20.69±0.89) μg of LS per tablet. SEM imaging revealed that the needle tips were conical. Additionally, Col-LS-DMNs exhibited favorable mechanical properties and caused minimal skin damage. After 24 hours, the cumulative permeation amount was (21.55±19.49) μg/cm2. Col-LS-DMNs significantly reduced MSU-induced ankle swelling and decreased serum concentrations of TNF-α, IL-6, and IL-1β in rats. In conclusion, Col-LS-DMNs represent a promising new treatment modality for GA.

Probiotic Bacillus cereus regulates metabolic disorders and activates the cholic acid-FXR axis to alleviate DSS-induced colitis

Inflammatory bowel disease is characterized by severe imbalance of intestinal flora and metabolic disorders. Recent studies have demonstrated that probiotics can effectively alleviate inflammatory bowel disease by restoring the intestinal flora structure and modulating the immune response. However, the role of probiotics in regulating intestinal metabolism disorders is still unclear. This study explores the role of probiotic B. cereus in alleviating DSS-induced colitis. The findings indicated probiotic B. cereus treatment mitigated tissue damage and apoptosis during inflammation. Metabolome and transcriptome analysis revealed B. cereus activated the cholic acid-FXR axis by increasing cholic acid levels, which promoted the gene expression level of NF-κB inhibitor α, reduced the IL-1β, IL-6, IL-18 and TNF-α concentrations. Furthermore, it effectively mitigated the DSS-induced disruption of bile acid metabolism, arginine metabolism, and linoleic acid metabolism. This study explores the effect and mechanisms of probiotic B. cereus on alleviating DSS-induced colitis. It aims to provide a theoretical basis for microbial therapy in inflammatory bowel disease. SignificanceThis study used metabolome and transcriptome to reveal the roles and mechanisms, which probiotic Bacillus cereus modulates metabolic disorders and alleviate DSS-induced colitis. We identified the cholic acid-FXR axis as an important target for alleviating DSS-induced colitis. These findings provide new insights into microbial treatment strategies for IBD.

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.

The IL-33/ST2 signaling axis drives pathogenesis in acute SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), remains a significant threat to global public health. Immunopathological damage plays a role in driving pneumonia, acute respiratory distress syndrome (ARDS), and multiorgan failure in severe COVID-19. Therefore, dissecting the pulmonary immune response to SARS-CoV-2 infection is critical to understand disease pathogenesis and identify immune pathways targetable by therapeutic intervention. Considering that the type 2 cytokine IL-13 enhances COVID-19 disease severity, therapeutic targeting of upstream signals that drive type 2 immunity may confer further protection. In this study, we investigate the role of the IL-33/ST2 signaling axis, a potent inducer of type 2 immunity in the lung, in a mouse model of COVID-19. Upon infection with mouse-adapted SARS-CoV-2 MA10, ST2 -/- mice had significantly improved weight loss and survival (69.2% vs 13.3% survival; P = 0.0005), as compared to wild-type mice. In a complementary pharmacologic approach, IL-33/ST2 signaling was inhibited using HpBARI_Hom2, a helminth derived protein that binds to mouse ST2 and blocks IL-33 signaling. In SARS-CoV-2 MA10 infection, HpBARI_Hom2-treated mice had significantly improved weight loss and survival (60% vs 10% survival; P = 0.0035), as compared to inert control-treated mice. These data demonstrate that loss of IL-33/ST2 signaling confers protection during acute SARS-CoV-2 MA10 infection, implicating the IL-33/ST2 signaling axis as an enhancer of COVID-19 disease severity. The protection conferred by pharmacologic blockade of IL-33/ST2 signaling was independent of viral control, as HpBARI_Hom2-treated mice had no reduction in viral titers. This finding suggests an immunopathogenic role for IL-33/ST2 signaling. One potential mechanism through which IL-33/ST2 signaling may drive severe disease is through enhancement of type 2 immune pathways including IL-5 production, as pulmonary IL-5 concentrations were found to depend on IL-33/ST2 signaling in acute SARS-CoV-2 MA10 infection.

Associations between glycan signature alterations and the cellular antigenic properties of passaged chondrocytes.

Cartilage repair is a significant clinical challenge because of the limited intrinsic healing capacity. Current therapeutic strategies, such as cell transplantation therapy, aim to overcome this challenge by replacing damaged tissue with healthy cells. However, the long-term survival and functionality of transplanted cells remain major hurdles. This study investigated the impact of chondrocyte passaging on glycan profiles and their antigenic properties. We hypothesized that alterations in glycan composition due to passaging may contribute to the enhanced ability to activate macrophages, thereby affecting the outcome of cell transplantation therapy. Peritoneal macrophages and primary articular chondrocytes were isolated from C57BL/6 mice to establish direct and indirect coculture models. Macrophage activation was assessed by measuring the concentrations of IL-6 and nitric oxide in the culture supernatants or their gene expression. Glycome analysis of various glycoconjugates was performed by glycoblotting methods combined with the SALSA procedure for N-glycans and GSLs and the BEP method for O-glycans. Our results revealed that direct coculture of macrophages with passaged chondrocytes increased the production of proinflammatory cytokines, including IL-6 and NO, as the number of passages increased. With increasing passage number, the expression of GD3 substantially decreased, and the expression of GM3, especially GD1a, significantly increased. Coculturing passaged GM3S knockout chondrocytes with macrophages significantly suppressed IL-6 expression, implying reduced macrophage activation. The observed activation of macrophages due to alterations in the glycan profile of chondrocytes provides a possible explanation for the antigenicity and immune rejection of transplanted cells.

External validation of a non-invasive vaginal tool to assess the risk of intra-amniotic inflammation in pregnant women with preterm labor and intact membranes.

To prospectively validate the diagnostic performance of a non-invasive point-of-care tool (Rapid IAI System), including vaginal alpha-fetoprotein and interleukin-6, to predict the occurrence of intra-amniotic inflammation in a Spanish cohort of patients admitted with a diagnosis of preterm labor and intact membranes. From 2017 to 2022, we prospectively evaluated a cohort of pregnant women diagnosed with preterm labor and intact membranes admitted below 34+0weeks who underwent amniocentesis to rule-in/out intra-amniotic infection and/or inflammation. Vaginal sampling was performed at the time of amniocentesis or within 24-48 h. Amniotic fluid IL-6, vaginal alpha-fetoprotein and vaginal IL-6 concentrations were measured using a point-of-care tool provided by Hologic Inc., "Rapid IAI System". We defined intra-amniotic inflammation when amniotic fluid IL-6 values were greater than 11.3 ng/mL. During recruitment, clinicians were blinded to the results of the point-of-care tool. The original prediction model proposed by Hologic Inc. to predict intra-amniotic inflammation was validated in this cohort of patients. We included 151 patients diagnosed with preterm labor and intact membranes. Among these, 29 (19.2 %) had intra-amniotic inflammation. The algorithm including vaginal IL-6 and alpha-fetoprotein showed an area under curve to predict intra-amniotic inflammation of 80.3 % (±5.3 %) with a sensitivity of 72.4 %, specificity of 84.6 %, positive predictive valuve (PPV) of 52.5 %, negative predictive value (NPV) of 92.9 %, and a positive likelihood ratio (LR+) of 4.6 and negative likelihood ratio (LR-) of 0.33. External validation of a non-invasive rapid point-of-care tool, including vaginal alpha-fetoprotein and IL-6, showed very good diagnostic performance for predicting the absence of intra-amniotic inflammation in women with preterm labor and intact membranes.

β-Nicotinamide Mononucleotide Alleviates Sepsis-associated Acute Kidney Injury by Activating NAD+/SIRT3 Signaling.

Acute kidney injury (AKI) following sepsis is a life-threatening condition that portends higher mortality. β-Nicotinamide mononucleotide (β-NMN), a crucial nicotinamide adenine dinucleotide (NAD+) precursor, exhibits the potential to against sepsis. We aimed to elucidate the effect of β-NMN on septic AKI. A cecal ligation and perforation (CLP)-induced sepsis-associated AKI mice model and a lipopolysaccharide (LPS)-triggered HK-2 cell model were established. Renal histopathology in mice with septic AKI without or with β-NMN treatment was detected using H&E staining. The contents of serum creatinine (Scr), blood urea nitrogen (BUN) and renal NAD+ were assessed with kits. Inflammation was evaluated by detecting the concentrations of TNF-α, IL-1β and IL-6 using ELISA kits. Besides, TUNEL assay was used to examine apoptosis and apoptosis-associated proteins was measured using immunoblotting. Additionally, expression of genes in sirtuins (SIRTs) family in renal tissues was tested using RT-qPCR. HK-2 cell viability was detected using CCK-8 assy. Finally, SIRT3 was silenced to carry out the rescue experiments. As a result, NAD+ level was decreased in kidney tissues of mice with sepsis-associated AKI and HK-2 cells treated with LPS. β-NMN treatment increased NAD+ level and alleviated the inflammation and apoptosis in renal tissues. It could be observed that SIRT3 expression was notably downregulated in vivo and in vitro, which was upregulated by β-NMN supplementation. Further, interfering with SIRT3 expression mitigated the protective effects of β-NMN on the inflammation and apoptosis of HK-2 cells under LPS conditions. In summary, β-NMN alleviates sepsis-associated AKI by activating NAD+/SIRT3 signaling. Our findings provide evidence of β-NMN supplementation on improvement of sepsis-associated AKI.

Exploring the landscape of symptom-specific inflammatory cytokines in post-COVID syndrome patients

IntroductionPost-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical symptoms as well as the endothelial function in PCS.MethodsOur analytical study involved all eligible patients (n = 66) with PCS included from April 2021 to December 2021. The serum concentration of cytokines IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-27, IP-10, MCP-1 and TNF-α was quantified by flow cytometry. Endothelial function was explored by assessing microvascular flow and reactivity using thermal probes. A comparative study was carried out according to the presence of each PCS symptom.ResultsThe average age of our patients was 55.9 ± 16.2 years. The sex ratio was 0.69. Forty-one patients (62%) presented with a severe form of acute infection. The most frequently reported symptoms were dyspnea (67%), fatigue (50%), and memory problems (32%). Fifty-seven patients (86%) had endothelial dysfunction. The majority of patients had increased levels of IP-10 (100%), IL-8 (95%), IFN-γ (95%), MCP-1 (80%), and TNF-α (70%). The serum concentration of IL-10 was below the threshold of quantification in 89% of subjects. The severe form of acute infection was associated with elevated IL-10, MCP-1, and IL-27. Increased IL-6 and IL-27 levels were associated with fatigue while IL-8 concentrations were higher in patients who reported dyspnea. Elevation of IL-8 level was more common in patients with profound impairment of endothelial function.ConclusionOur results further support the presence of endothelial dysfunction in PCS and show an elevation of pro-inflammatory cytokines with a downmodulation of the IL-10- anti-inflammatory response. In addition, immuno-clinical phenotypes emerge, such as an inflammatory profile mediated by IL-6 and IL-27 in fatigue and IL-8 in dyspnea. The identification of immuno-clinical phenotypes would allow a better understanding of the pathophysiology of PCS symptoms.

Serum IL-6 and TGF-β1 concentrations as diagnostic biomarkers in elderly male patients with osteoporosis.

This research is intended to evaluate the correlations of serum IL-6 and TGF-β1 concentrations with bone density and turnover markers as well as their diagnostic value in elderly male patients with osteoporosis (OP). A retrospective analysis was conducted on 335 elderly men (≥ 60years; 90 with normal bone mass, 120 osteopenia cases, and 125 OP cases). Lumbar spine/femoral neck BMD values were measured using dual-energy X-ray absorptiometry. Correlations of serum IL-6 and TGF-β1 concentrations with bone density and bone turnover markers in OP patients were analyzed utilizing Pearson or Spearman correlation coefficients. Independent influencing factors for OP were identified by logistic multivariate regression analysis. The diagnostic value of serum IL-6 and TGF-β1 was assessed with ROC curves and MedCalc software. Smoking history, drinking history, lumbar spine BMD, femoral neck BMD, PINP, and β-CTX markedly differed among the normal bone mass, osteopenia, and OP groups. Elevated IL-6 and reduced TGF-β1 concentrations were observed in serum samples of OP. Serum IL-6 concentrations was inversely associated with bone density markers but positively lined to bone turnover markers. Conversely, serum TGF-β1 was positively related to bone density markers but negatively associated with bone turnover markers. Smoking history, PINP, and IL-6, were identified as independent risk factors while lumbar spine BMD, femoral neck BMD, and TGF-β1 were independent protective markers for OP. The combined assessment of serum IL-6 and TGF-β1 showed superior diagnostic performance for OP. Serum IL-6 in combination with TGF-β1 exhibits good diagnostic performance for OP. Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Serum Concentrations of Pro- and Anti-Inflammatory Cytokines in Wistar Rats Subjected to Immobilization Stress and Treated with Tuftsin-Pro-Gly-Pro Peptide.

It was found that 28-day immobilization stress in male Wistar rats leads to significant increase in the serum concentrations of proinflammatory cytokines IL-1β, IL-6, IFNγ, and monocyte chemoattractant protein-1 (MCP-1) and a decrease in the content of anti-inflammatory IL-10, as well as the ratio IL-1β/IL-10, IL-6/IL-10, and IFNγ/IL-10 compared to non-stressed animals. Administration of the heptapeptide tuftsin-Pro-Gly-Pro produced a corrective effect on cytokine concentrations under stress conditions: at a dose of 750 μg/kg, the peptide decreased the concentrations of IL-1β, IFNγ, and MCP-1 and cytokine ratios (IL-1β/IL-10 and IFNγ/IL-10), while at a dose of 250 μg/kg, it increased IL-10 levels and decreased IL-6/IL-10 and IFNγ/IL-10 ratios.

Increased Concentrations of Dopamine in the Blood and the State of the Immune System in Practically Healthy Residents of the Northern Territories

The numerous effects of dopamine are predetermined by the fact that it, being a chemical precursor of noradrenaline, is secreted in nervous tissue, in the adrenal medulla, kidneys, intestines, and APUD cells (Apudocytes). The purpose of the work is to study the effectiveness of immune reactions at elevated concentrations of dopamine in the blood of practically healthy residents of the northern territories. The results of an immunological examination of 1064 practically healthy people aged 25-55 years living in the Arkhangelsk and Murmansk regions, as well as in the Nenets Autonomous Okrug, the Komi Republic and the Svalbard archipelago (Barentsburg) were analyzed. It was found that elevated concentrations of dopamine in peripheral venous blood were more often recorded in Arctic residents; during the polar day, dopamine concentrations are higher than in winter. Increased concentrations of dopamine in the blood of Northerners are associated with a decrease in the level of activated T cells with the transferrin receptor and IL-2, T-helper cells, as well as with increased concentrations of IL-1β, TNF-α, cortisol and thyroxine. An increase in dopamine concentration may be a consequence of a cytokine reaction in the nervous tissue to inhibit excessive receptor activity of cells by increasing the concentration of IL-10. The formation of an excess of both central hormones secreted by the pituitary gland and peripheral hormones at the same time is probably due to an increase in the sensitivity threshold of the hypothalamus, which is associated with an increase in the flow of interoceptive impulses of afferent systems.