Lower Levels Of IL-6 Research Articles

Utilization of experimental design in the formulation and optimization of hyaluronic acid–based nanoemulgel loaded with a turmeric–curry leaf oil nanoemulsion for gingivitis

Numerous problems affect oral health, and intensive research is focused on essential oil–based nanoemulsions that might treat prevent or these problems. Nanoemulsions are delivery systems that enhance the distribution and solubility of lipid medications to targeted locations. Turmeric (Tur)- and curry leaf oil (CrO)–based nanoemulsions (CrO-Tur-self-nanoemulsifying drug delivery systems [SNEDDS]) were developed with the goal of improving oral health and preventing or treating gingivitis. They could be valuable because of their antibacterial and anti-inflammatory capabilities. CrO-Tur-SNEDDS formulations were produced using the response surface Box-Behnken design with different concentrations of CrO (120, 180, and 250 mg), Tur (20, 35, and 50 mg), and Smix 2:1 (400, 500, and 600 mg). The optimized formulation had a bacterial growth inhibition zone of up to 20 mm, droplet size of less than 140 nm, drug-loading efficiency of 93%, and IL-6 serum levels of between 950 ± 10 and 3000 ± 25 U/ml. The optimal formulation, which contained 240 mg of CrO, 42.5 mg of Tur, and 600 mg of Smix 2:1, was created using the acceptable design. Additionally, the best CrO-Tur-SNEDDS formulation was incorporated into a hyaluronic acid gel, and thereafter it had improved ex-vivo transbuccal permeability, sustained in-vitro release of Tur, and large bacterial growth suppression zones. The optimal formulation loaded into an emulgel had lower levels of IL-6 in the serum than the other formulations evaluated in rats. Therefore, this investigation showed that a CrO-Tur-SNEDDS could provide strong protection against gingivitis caused by microbial infections.

Seluang Fish (Rasbora sp.) Oil Improves Interleukin-17 Levels and Disease Activity in Rheumatoid Arthritis

BACKGROUND: Vitamin D has a role in downregulating the proinflammatory cytokines as well as promoting the antiinflammatory pathway in rheumatoid arthritis (RA). Seluang fish (Rasbora sp.) has potency as a new source of vitamin D. Previous study had proven Seluang fish oil efficacy in systemic lupus erythematosus. However, there are no trials that prove its efficacy in RA yet. Hence, this study was conducted to find out the ability of Seluang fish oil to improve proinflammatory cytokines, vitamin D levels, and disease activity in RA.METHODS: A clinical trial with a randomized and double-blind method was done in two groups, each one consisting of 17 RA subjects. One group was given 500 mL of a Seluang fish oil capsule (contains 665 IU cholecalciferol), while the other group was given a placebo daily, for 12 consecutive weeks. Measurements of the RA disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR) and DAS28 C-reactive protein (DAS28-CRP), as well as measurement of interleukin (IL)-6, IL-17, and vitamin D levels by using immunoassay method were performed before and after the supplementation.RESULTS: Significant alterations in the lower levels of IL-17 were observed in the Seluang fish oil group (p=0.031), but not in the placebo group (p=0.320). Reduction of DAS28-ESR (p=0.000) and DAS28-CRP (p=0.000) score demonstrated that the Seluang fish oil supplementation was useful in reducing RA disease activity. No significant shift was observed in either vitamin D (p=0.967) or IL-6 levels (p=0.076) after Seluang Fish Oil supplementation.CONCLUSION: Seluang fish oil is effective in lowering IL-17 levels, DAS28-ESR, and DAS28-CRP, but not in improving vitamin D level or lowering IL-6 level in RA patients.KEYWORDS: rheumatoid arthritis, seluang fish oil, interleukin-6, interleukin-17, vitamin D, DAS28

Major Depressive Disorder and Pulmonary Tuberculosis Comorbidity Exacerbates Proinflammatory Immune Response—A Preliminary Study

Major depressive disorders (MDDs) occurs frequently in patients with tuberculosis (TB). Elevated serum pro-inflammatory cytokine levels in MDD patients is a well-established fact. Therefore, an integrated clinical practice should be considered. However, the inflammatory status of MDD-TB patients is unknown. In this study, we analyze cytokines in activated-cells and sera from MDD-TB, TB, MDD patients, and healthy controls. Flow cytometry was used to evaluate the intracellular production of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, and IL-10 by peripheral blood mononuclear cells after a polyclonal stimulation. A Bio-Plex Luminex system was used to measure serum cytokine and chemokine levels in the study groups. We observed a 40.6% prevalence of MDD in TB patients. The proportion of IFN-gamma-producing cells was higher in MDD-TB patients than other pathological groups. Nevertheless, the percentage of TNF-alpha- and IL-12-producing cells was similar between MDD-TB and TB patients. Likewise, MDD-TB and TB patients showed similar serum pro-inflammatory cytokine and chemokine levels, which were significantly lower than those in MDD patients. By multiple correspondence analyses, we observed that low levels of serum IL-4, IL-10, and IL-13 were powerfully associated with TB comorbidities with MDD. A high frequency of IFN-γ-producing cells is associated with low levels of serum anti-inflammatory cytokines in MDD-TB patients.

Exploring drug repositioning for leishmaniasis treatment: Ivermectin plus polymeric micelles induce immunological response and protection against tegumentary leishmaniasis

Leishmania amazonensis can cause a wide spectrum of the clinical manifestations of leishmaniasis in humans. The development of new therapeutics is a long and expensive task; in this context, drug repositioning could be considered a strategy to identify new biological actions of known products. In the present study, ivermectin (IVE) was tested against distinct Leishmania species able to cause disease in humans. In vitro experiments showed that IVE was effective to reduce the infection degree and parasite load in Leishmania donovani- and L. amazonensis-infected macrophages that were treated with it. In addition, using the culture supernatant of treated macrophages, higher production of IFN-γ and IL-12 and lower levels of IL-4 and IL-10 were found. Then, IVE was used in a pure form or incorporated into Poloxamer 407-based polymeric micelles (IVE/M) for the treatment of L. amazonensis-infected BALB/c mice. Animals (n = 16 per group) were infected and later received saline, empty micelles, amphotericin B (AmpB), IVE, or IVE/M. They were euthanized at one (n = 8 per group) and 30 (n = 8 per group) days after treatment and, in both endpoints, immunological, parasitological, and biochemical evaluations were performed. Results showed that both IVE and IVE/M induced higher levels of IFN-γ, IL-12, GM-CSF, nitrite, and IgG2a antibodies, as well as higher IFN-γ expression evaluated by RT-qPCR in spleen cell cultures. Such animals showed low organic toxicity, as well as significant reductions in the lesion’s average diameter and parasite load in their infected tissue, spleen, liver, and draining lymph node. The efficacy was maintained 30 days post-therapy, while control mice developed a polarized Th2-type response and high parasite load. In this context, IVE could be considered as a new candidate to be applied in future studies for the treatment against distinct Leishmania species.

Effect of Cancer-Related Cachexia and Associated Changes in Nutritional Status, Inflammatory Status, and Muscle Mass on Immunotherapy Efficacy and Survival in Patients with Advanced Non-Small Cell Lung Cancer

Immune checkpoint inhibitor (ICI)-based immunotherapy has significantly improved the survival of patients with advanced non-small cell lung cancer (NSCLC); however, a significant percentage of patients do not benefit from this approach, and predictive biomarkers are needed. Increasing evidence demonstrates that cachexia, a complex syndrome driven by cancer-related chronic inflammation often encountered in patients with NSCLC, may impair the immune response and ICI efficacy. Herein, we carried out a prospective study aimed at evaluating the prognostic and predictive role of cachexia with the related changes in nutritional, metabolic, and inflammatory parameters (assessed by the multidimensional miniCASCO tool) on the survival and clinical response (i.e., disease control rate) to ICI-based immunotherapy in patients with advanced NSCLC. We included 74 consecutive patients. Upon multivariate regression analysis, we found a negative association between IL-6 levels (odds ratio (OR) = 0.9036; 95%CI = 0.8408-0.9711; p = 0.0025) and the miniCASCO score (OR = 0.9768; 95%CI = 0.9102-0.9999; p = 0.0310) with the clinical response. As for survival outcomes, multivariate COX regression analysis found that IL-6 levels and miniCASCO-based cachexia severity significantly affected PFS (hazard ratio (HR) = 1.0388; 95%CI = 1.0230-1.0548; p < 0.001 and HR = 1.2587; 95%CI = 1.0850-1.4602; p = 0.0024, respectively) and OS (HR = 1.0404; 95%CI = 1.0221-1.0589; p < 0.0001 and HR = 2.3834; 95%CI = 1.1504-4.9378; p = 0.0194, respectively). A comparison of the survival curves by Kaplan-Meier analysis showed a significantly lower OS in patients with cachexia versus those without cachexia (p = 0.0323), as well as higher miniCASCO-based cachexia severity (p = 0.0428), an mGPS of 2 versus those with a lower mGPS (p = 0.0074), and higher IL-6 levels (>6 ng/mL) versus those with lower IL-6 levels (≤6 ng/mL) (p = 0.0120). In conclusion, our study supports the evidence that cachexia, with its related changes in inflammatory, body composition, and nutritional parameters, is a key prognostic and predictive factor for ICIs. Further larger studies are needed to confirm these findings and to explore the potential benefit of counteracting cachexia to improve immunotherapy efficacy.

The Interplay of Type 1, Type 2, and Type 3 Lymphocytes and Cytokines in Atopic Dermatitis

Atopic dermatitis (AD) is classified as a type 2 disease owing to the majority of type 2 lymphocytes that constitute the skin-infiltrating leukocytes. However, all of the type 1-3 lymphocytes intermingle in inflamed skin lesions. Here, using an AD mouse model where caspase-1 was specifically amplified under keratin-14 induction, we analyzed the sequential changes in type 1-3 inflammatory cytokines in lymphocytes purified from the cervical lymph nodes. Cells were cultured and stained for CD4, CD8, and γδTCR, followed by intracellular cytokines. Cytokine production in innate lymphocyte cells (ILCs) and the protein expression of type 2 cytokine IL-17E (IL-25) were investigated. We observed that, as inflammation progresses, the cytokine-producing T cells increased and abundant IL-13 but low levels of IL-4 are produced in CD4-positive T cells and ILCs. TNF-α and IFN-γ levels increased continuously. The total number of T cells and ILCs peaked at 4 months and decreased in the chronic phase. In addition, IL-25 may be simultaneously produced by IL-17F-producing cells. IL-25-producing cells increased in a time-dependent manner during the chronic phase and may work specifically for the prolongation of type 2 inflammation. Altogether, these findings suggest that inhibition of IL-25 may be a potential target in the treatment of inflammation.

ACTIVITY OF RED GINGER EXTRACT (ZINGIBER OFFICINALE VAR. RUBRUM) AGAINST INTERLEUKIN-6

Objective: Knowing that it contains gingerol chemicals, red ginger (Zingiber officinale var. Rubrum) has the potential as a natural immunomodulator. Immunomodulating substances can affect how the human immune system responds by helping to keep the body in a homeostatic state and rebalancing immune system imbalances. The goal of this study was to find out of the extract of red ginger inoculated by Arbuscular Mycorrhizal Fungi (FMA) in different concentrations affected the reduction of IL-6 levels in test animals' serum in vivo.&#x0D; Methods: Twenty-four white male mice were used in this study. Additionally, they were split into six groups, with the negative control group received 0.5% Na CMC. The experimental group received red ginger extract at doses of 100 mg/kgBW, 200 mg/kgBW, 400 mg/kgBW, and "Stimuno" 50 mg/kgBW, whereas the positive control received the Pfizer vaccine. The Pfizer vaccination was administered intramuscularly on day 0 to experimental animals in the positive control and experimental groups. Following that, they underwent a 14-day oral red ginger extract test. Using the Enzyme-linked immunosorbent assay (ELISA) technique, the test was carried out to measure the concentration of IL-6 in the serum.&#x0D; Results: The findings illustrated that the dose variations of 100, 200, and 400 mg/kgBW had a significant impact on the drop in IL-6 levels (p&lt;0.05).&#x0D; Conclusion: The findings indicate that red ginger ethanol extract, in a variety of dosages, may lower IL-6 levels. The largest reduction in IL-6 levels was seen in the extract test group at a dose of 100 mg/kgBW.

Nasal biomarkers of immune function differ based on smoking and respiratory disease status.

Respiratory biomarkers have the potential to identify airway injury by revealing inflammatory processes within the respiratory tract. Currently, there are no respiratory biomarkers suitable for clinical use to identify patients that warrant further diagnostic work-up, counseling, and treatment for toxic inhalant exposures or chronic airway disease. Using a novel, noninvasive method of sampling the nasal epithelial lining fluid, we aimed to investigate if nasal biomarker patterns could distinguish healthy nonsmoking adults from active smokers and those with chronic upper and lower airway disease in this exploratory study. We compared 28 immune mediators from healthy nonsmoking adults (n=32), former smokers with COPD (n=22), chronic rhinosinusitis (CRS) (n=22), and smoking adults without airway disease (n=13). Using ANOVA, multinomial logistic regressions, and weighted gene co-expression network analysis (WGCNA), we determined associations between immune mediators and each cohort. Six mediators (IL-7, IL-10, IL-13, IL-12p70, IL-15, and MCP-1) were lower among disease groups compared to healthy controls. Participants with lower levels of IL-10, IL-12p70, IL-13, and MCP-1 in the nasal fluid had a higher odds of being in the COPD or CRS group. The cluster analysis identified groups of mediators that correlated with disease status. Specifically, the cluster of IL-10, IL-12p70, and IL-13, was positively correlated with healthy and negatively correlated with COPD groups, and two clusters were correlated with active smoking. In this exploratory study, we preliminarily identified groups of nasal mucosal mediators that differed by airway disease and smoking status. Future prospective, age-matched studies that control for medication use are needed to validate these patterns and determine if nasosorption has diagnostic utility for upper and lower airway disease or injury.

Correlation of high serum interleukin-6 with clinical outcome and T cell response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

596 Background: We elucidated the clinical and immunologic implications of serum interleukin (IL)-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev). Methods: We prospectively enrolled 165 patients with unresectable HCC (Discovery cohort: 84 patients from three centers; Validation cohort: 81 patients from one center). Baseline blood samples were analyzed using a flow cytometric bead array. The tumor immune microenvironment was analyzed using RNA sequencing. Results: In the Discovery cohort, clinical benefit (CB) was defined as a complete or partial response or stable disease for ≥ 6 months. Among various blood-based biomarkers, the serum IL-6 level was significantly higher in patients without CB than in those with CB (mean 11.56 vs. 5.05 pg/mL, P=0.02). The optimal cutoff value for high IL-6 was determined as 18.49 pg/mL using maximally selected rank statistics, and 15.2% of patients were identified to have high IL-6 levels at baseline. In both the Discovery and Validation cohorts, patients with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev compared with that of patients with low IL-6 levels. In the multivariable Cox regression analysis, the clinical implication of high IL-6 levels persisted even after adjustment for various confounding factors. Patients with high IL-6 levels showed reduced interferon-γ and tumor necrosis factor-α secretion from CD8+ T cells. Moreover, excess IL-6 suppressed cytokine production and CD8+ T-cell proliferation. Finally, patients with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumor microenvironment. Conclusions: High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment.

Frequency of IRF5+ dendritic cells is associated with the TLR7-induced inflammatory cytokine response in SARS-CoV-2 infection.

The SARS-CoV-2 infection leads to enhanced inflammation driven by innate immune responses. Upon TLR7 stimulation, dendritic cells (DC) mediate the production of inflammatory cytokines, and in particular of type I interferons (IFN). Especially in DCs, IRF5 is a key transcription factor that regulates pathogen-induced immune responses via activation of the MyD88-dependent TLR signaling pathway. In the current study, the frequencies of IRF5+ DCs and the association with innate cytokine responses in SARS-CoV-2 infected individuals with different disease courses were investigated. In addition to a decreased number of mDC and pDC subsets, we could show reduced relative IRF5+ frequencies in mDCs of SARS-CoV-2 infected individuals compared with healthy donors. Functionally, mDCs of COVID-19 patients produced lower levels of IL-6 in response to in vitro TLR7 stimulation. IRF5+ mDCs more frequently produced IL-6 and TNF-α compared to their IRF5- counterparts upon TLR7 ligation. The correlation of IRF5+ mDCs with the frequencies of IL-6 and TNF-α producing mDCs were indicators for a role of IRF5 in the regulation of cytokine responses in mDCs. In conclusion, our data provide further insights into the underlying mechanisms of TLR7-dependent immune dysfunction and identify IRF5 as a potential immunomodulatory target in SARS-CoV-2 infection.

Immunomodulatory effects of bone marrow-derived Mesenchymal stem cells on BALB/c mice model with induced Systemic lupus erythematosus (SLE).

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease that causes acute inflammation in most body tissues. The current study aims to determine levels of some cytokines and chemokines in BALB/c mice with SLE and treatment by using BALB/c Mesenchymal stem cells (BM-MSCs). Forty BALB/c male mice were divided into four groups equally. The first and second groups received activated lymphocyte-derived DNA (ALD DNA) for induction of SLE. The second group received BM-MSCs/IV after the appearance of SLE clinical signs. The third group received BM-MSCs only, while the fourth group (control group) received PBS. All the study groups examine levels of IL-10, IL-6, TGFβ1, VEGF, CCL-2, CCL-5/RANTES, IFNγ, and ICAM -1 by ELISA kits. The cytokines levels are determined in all the study groups. There was a significant increase in ANA and anti-dsDNA levels in the first group, while there was a decrease in the second group (treatment by BM-MSCs). There is no significant difference between the third and control groups in ANA and anti-dsDNA levels. The first group showed a significant increase in IL-6, CCL-5/RANTES, VEGF, ICAM, CCL-2, and IFNγ levels and a decrease in IL-10 and TGFβ1. The second group showed low levels of IL-6, CCL-5/RANTES, VEGF, ICAM, CCL-2/MCP-1, and IFNγ but a high level of IL-10 and TGFβ1 as compared with the control group. The third group has no significant differences from the control group in all the tested parameters. BM-MSCs have an essential therapeutic role in the functional regulation of cytokines and chemokines in mice with SLE.

P033 The assessment of serum cytokines at baseline could predict mucosal healing in patients with Crohn’s disease treated with ustekinumab. A prospective study.

Abstract Background Ustekinumab (UST) is a monoclonal IgG1 antibody binding the p40 subunit of IL-12 and IL-23. The blockage of the activation of the heterodimer IL-12/IL-23 inhibits the differentiation of Th1 and Th17 cells, reducing the inflammatory cascade typical of Crohn’s disease (CD). Some patients with CD achieve mucosal healing after one year of UST therapy, whereas others experience primary non-response or loss of response. No biomarkers are currently available to predict therapeutic response to UST. The aim of this prospective study was to identify one or more biomarkers able to predict mucosal healing in patients with CD treated with UST. Methods We prospectively enrolled all consecutive CD patients treated with UST, following the current guidelines. A blood sample was drawn before UST infusion at week 0 (baseline), 24 and 48, and serum cytokines IL1α, IL-1β, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IL-22, IL-23 and IL-33 were evaluated by a fluorescence assay. At the same timepoints, Fecal Calprotectin (FC) was assessed. A colonoscopy was performed before starting the treatment and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing, defined as a Simple Endoscopic Score for CD &amp;lt;2. Results Out of 44 patients enrolled, 22 (50%) achieve mucosal healing at the end of follow up. Baseline IL-23 levels were higher in responders than in non-responders (Mann-Whitney test, p-value&amp;lt;0.001), whereas higher baseline levels of IL-1α are associated with non-response (p=0.03). We also observed a higher probability of mucosal healing in those with lower levels of IL-6 at baseline (p=0.05). A borderline statistically significant association was observed for baseline FC, which values were lower in responders than in non-responders (Mann-Whitney test, p=0.098). No significant differences were observed with regard to the baseline levels of the other cytokines. FC levels decreased over time in responders, whereas its values did not change over time in non-responders (test for the interaction between time and outcome, p&amp;lt;0.001). IL-13 presented a homogenously decreasing time trend regardless the outcomes (test for the association with time and outcome, p=0.019). No significant time trend was observed with regard to the other cytokines. Conclusion Baseline serum levels of IL-23, IL-1α and IL-6, as well as the decrease of FC over time, showed a good reliability in predicting therapeutic outcome to UST in CD in terms of mucosal healing. These biomarkers could help clinicians in the perspective of a better management of UST therapy, identifying early the patients with higher probability to respond to the treatment.

Reproducibility of the new Leishmania vaccine: Changes in T1, T2 and spleen white pulp responses after re- exposure to live promastigote of Leishmania major

Introduction: Human leishmaniasis is distributed worldwide and is mainly in the tropics and subtropics, with a prevalence of 12 million cases and an approximately incidence of 0.5 million cases of VL and 1.5 million cases of cutaneous leishmaniasis (CL). Leishmania parasites are vector-born protozoan pathogens found in tropical and subtropical regions of both the old and new world. The disease in human can be divided into cutaneous, visceral, and mucosal syndromes. The aim of this study was more experiments over our previous new formulation leishmania major vaccine which had satisfactory experiments results. Method: For detail procedure refers to author’s previous publications. Briefly, hundred and twenty Balb/cmice were randomly divided into four groups as LT, LB, LBT and control groups. LT, LB and LBT injected subcutaneously with the antigen and the same booster doses with two weeks intervals. The expansion rates of the spleen white pulp size was evaluated using a light microscope and the levels of the serum Th1 (IFN- γ, IL-12) and Th2 (IL-4, IL-10) cytokines measured with the ELISA method. Results: Comparing to the LT and LB groups, the LBT group had highest levels of serum IL12, lowest levels of IL10 and highest increase in the spleen white pulp size. Significant correlation was observed between IL12 and IL10 but not IFN gamma or IL4. Conclusion: present study indicated that the LBT group which received crude cocktail leishmania antigen plus alcoholic extract of Teucrium polium and BCG as adjuvant showed satisfactory cytokines profile comparing to groups LT and LB,since highest levels of IL12 and lower levels of IL10 which could help the infected subjects to inhibit or eradication the intracellular leishmania amastigotes, and also was seen highest increase in the spleen white-pulp size which pointed to the synergistic effects of alcoholic extract of T. polium and BCG.

Lower Creatine Kinase, IL-6 Levels and Femoral Offset Values Lead to Better Outcome Harris Hip Score Post Bipolar Hemiarthroplasty Surgery Day 14 and Day 30

Bipolar Hemiarthroplasty (HA) procedure allows patients after a neck femur fracture to be able to perform early mobilization. Hence complications due to prolonged bed rest could be prevented. Early mobilization should be achieved immediately after bipolar HA surgery. There are several factors affecting early mobilization in patients, some of which include tissue damage during surgery (creatine kinase), inflammatory status of patients (IL-6) and implant position (femoral offset). This study aims to show whether lower levels of creatine kinase, IL-6 and femoral offset can result in better Harris Hip Score following Bipolar HA surgery day 14 and day 30. By knowing the influencing factors, it is hoped that more accurate management could be carried out. Thus, the outcome parameters of early mobilization in the form of returning to daily life and work activities are getting better and the risk of complications can be avoided. This study compared the Harris Hip Score (HHS) in patients who'd already had Bipolar Hemiarthroplasty using a prospective cohort study design (Bipolar HA) who met the inclusion criteria at the Central General Hospital (RSUP) Prof I.G.N.G Ngoerah Denpasar and provided them informed consent. In order to do descriptive analysis, normality and homogeneity tests, and proportion comparison analysis, the research data was entered into a research sheet and processed using a computer and the SPSS for Windows version 26 program. In this study, the sample data (n=32) was not normally distributed. Lower levels of IL-6 (&lt; 15 pg/ml), and FO values ​​(​​&lt; 42.5 mm) resulted in better HHS values ​​in patients following Bipolar HA surgery day-14. Additionally, lower levels of CK (&lt; 75 U/L), IL-6 (&lt; 15 pg/ml), and FO values (​​&lt; 42.5 mm) ​​resulted in better HHS values ​​in patients following bipolar HA surgery on day-30. Chi-Square analysis showed that the results of CK levels day-14 were statistically insignificant (p= 0.072&gt;0.05), while the results of CK levels day-30 were statistically significant (p=0.033&lt;0.05). Moreover, chi-Square analysis showed that the results of day-14 and day-30 were statistically significant on IL-6 levels (p-0.016&lt;0.05 and p= 0.015&lt;0.05), and FO values (p= 0.012&lt;0.05 and p-0.033&lt;0.05). It is concluded that lower levels of IL-6, and FO values resulted in better HHS values in patients following Bipolar HA surgery day-14. Additionally, lower levels of CK, IL-6, and FO values resulted in better HHS values in patients following bipolar HA surgery on day-30.

Enhanced Solubility and Biological Activity of Dexibuprofen-Loaded Silica-Based Ternary Solid Dispersions.

The current study was designed to formulate ternary solid dispersions (TSDs) of dexibuprofen (Dex) by solvent evaporation to augment the solubility and dissolution profile, in turn providing gastric protection and effective anti-inflammatory activity. Initially, nine formulations (S1 to S9) of binary solid dispersions (BSDs) were developed. Formulation S1 comprising a 1:1 weight ratio of Dex and Syloid 244FP® was chosen as the optimum BSD formulation due to its better solubility profile. Afterward, 20 TSD formulations were developed using the optimum BSD. The formulation containing Syloid 244FP® with 40% Gelucire 48/16® (S18) and Poloxamer 188® (S23) successfully enhanced the solubility by 28.23 and 38.02 times, respectively, in pH 6.8, while dissolution was increased by 1.99- and 2.01-fold during the first 5 min as compared to pure drug. The in vivo gastroprotective study in rats suggested that the average gastric lesion index was in the order of pure Dex (8.33 ± 2.02) > S1 (7 ± 1.32) > S18 (2.17 ± 1.61) > S23 (1.83 ± 1.04) > control (0). The in vivo anti-inflammatory study in rats revealed that the percentage inhibition of swelling was in the order of S23 (71.47 ± 2.16) > S18 (64.8 ± 3.79) > S1 (54.14 ± 6.78) > pure drug (18.43 ± 2.21) > control (1.18 ± 0.64) after 6 h. ELISA results further confirmed the anti-inflammatory potential of the developed formulation, where low levels of IL-6 and TNF alpha were reported for animals treated with S23. Therefore, S23 could be considered an effective formulation that not only enhanced the solubility and bioavailability but also reduced the gastric irritation of Dex.

Post-vaccination serum cytokines levels correlate with breakthrough influenza infections

Post-vaccination cytokine levels from 256 young adults who subsequently suffered breakthrough influenza infections were compared with matched controls. Modulation within the immune system is important for eliciting a protective response, and the optimal response differs according to vaccine formulation and delivery. For both inactivated influenza vaccine (IIV) and live attenuated influenza vaccines (LAIV) lower levels of IL-8 were observed in post-vaccination sera. Post-vaccination antibody levels were higher and IFN-γ levels were lower in IIV sera compared to LAIV sera. Subjects who suffered breakthrough infections after IIV vaccination had higher levels of sCD25 compared to the control group. There were differences in LAIV post-vaccination interleukin levels for subjects who subsequently suffered breakthrough infections, but these differences were masked in subjects who received concomitant vaccines. Wide variances, sex-based differences and confounders such as concomitant vaccines thwart the establishment of specific cytokine responses as a correlate of protection, but our results provide real world evidence that the status of the immune system following vaccination is important for successful vaccination and subsequent protection against disease.

High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma

We elucidated the clinical and immunologic implications of serum IL-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev). We prospectively enrolled 165 patients with unresectable HCC (discovery cohort: 84 patients from three centres; validation cohort: 81 patients from one centre). Baseline blood samples were analysed using a flow cytometric bead array. The tumour immune microenvironment was analysed using RNA sequencing. In the discovery cohort, clinical benefit 6 months (CB6m) was defined as complete or partial response, or stable disease for ≥6 months. Among various blood-based biomarkers, serum IL-6 levels were significantly higher in participants without CB6m than in those with CB6m (mean 11.56 vs. 5.05pg/ml, p= 0.02). Using maximally selected rank statistics, the optimal cut-off value for high IL-6 was determined as 18.49pg/ml, and 15.2% of participants were found to have high IL-6 levels at baseline. In both the discovery and validation cohorts, participants with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev treatment compared with those with low baseline IL-6 levels. In multivariable Cox regression analysis, the clinical implications of high IL-6 levels persisted, even after adjusting for various confounding factors. Participants with high IL-6 levels showed reduced interferon-γ and tumour necrosis factor-α secretion from CD8+ T cells. Moreover, excess IL-6 suppressed cytokine production and proliferation of CD8+ T cells. Finally, participants with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumour microenvironment. High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment. Although patients with hepatocellular carcinoma who respond to treatment with atezolizumab and bevacizumab exhibit favourable clinical outcomes, a fraction of these still experience primary resistance. We found that high baseline serum levels of IL-6 correlate with poor clinical outcomes and impaired T-cell response in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Effect of Familial Longevity on Frailty and Sarcopenia: A Case-Control Study.

Familial longevity confers advantages in terms of health, functionality, and longevity. We sought to assess potential differences in frailty and sarcopenia in older adults according to a parental history of extraordinary longevity. A total of 176 community-dwelling subjects aged 65-80 years were recruited in this observational case-control study, pair-matched 1:1 for gender, age, and place of birth and residence: 88 centenarians' offspring (case group) and 88 non-centenarians' offspring (control group). The main variables were frailty and sarcopenia based on Fried's phenotype and the European Working Group on Sarcopenia in Older People (EWGSOP) definitions, respectively. Sociodemographics, comorbidities, clinical and functional variables, the presence of geriatric syndromes, and laboratory parameters were also collected. Related sample tests were applied, and conditional logistic regression was performed. Cases had a higher percentage of robust patients (31.8% vs. 15.9%), lower percentages of frailty (9.1% vs. 21.6%) and pre-frailty (59.1% vs. 62.5%) (p = 0.001), and lower levels of IL-6 (p = 0.044) than controls. The robust adjusted OR for cases was 3.00 (95% CI = 1.06-8.47, p = 0.038). No significant differences in muscle mass were found. Familial longevity was also associated with less obesity, insomnia, pain, and polypharmacy and a higher education level and total and low-density lipoprotein cholesterol. The results suggest an inherited genetic component in the frailty phenotype, while the sarcopenia association with familial longevity remains challenging.

Irisin prevents hypoxic-ischemic brain damage in rats by inhibiting oxidative stress and protecting the blood-brain barrier

Hypoxic-ischemic encephalopathy (HIE) is associated with excessive inflammation, blood-brain barrier dysfunction, and oxidative stress. Irisin can reduce inflammation and ameliorate oxidative stress; however, its effects on hypoxic-ischemic brain damage in newborns are unknown. Newborn Sprague-Dawley rats were subjected to hypoxic-ischemic injury and irisin treatment. TUNEL staining assays, the albumin-Evans blue dye extravasation method, an antioxidants detection kit, quantitative reverse-transcriptase PCR, enzyme linked immunosorbent assay, Western blot analysis, immunohistochemistry, and electron microscopy were used to investigate the possible mechanisms underlying the prevention of HIE by irisin. We discovered that rats affected by HIE and administered irisin had lower levels of IL-6 (but not TNF-α or IL-1β) less oxidative stress, and enhanced blood-brain barrier integrity. Irisin can effectively attenuate brain damage by reducing oxidative stress and protecting the blood-brain barrier.

Immunoprotective effect of recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice

To evaluate the immunoprotective effect of active immunization with recombinant peptidyl-prolyl cis-trans isomerase from Babesia microti against B. microti infection in mice. Female BALB/c mice at 6 weeks of age, each weighing approximately 20 g, were divided into the recombinant protein immunization group, the infection control group and the normal control group, of 25, 18, 15 mice in each group, respectively. Mice in the recombinant protein immunization group were given active immunization with recombinant BmPPIase protein, and 18 mice with the highest antibody titers were intraperitoneally injected with 100 μL of B. microti-infected whole blood 2 weeks after the last immunization. Mice in the infection control group were intraperitoneally injected with 100 μL of B. microti-infected whole blood, while 15 mice in the normal control group received no treatment. Blood samples were collected from mice in the recombinant protein immunization group and the infection control group on days 0 to 30 post-immunization for detection of B. microti infection, and blood samples were collected on days 0, 7, 14, 21, and 28 post-immunization for routine blood tests with a blood cell analyzer and for detection of serum cytokines using cytometric bead array. Anti-BmPPIase antibodies were detected in 25 mice in the recombinant protein immunization group 2 weeks after the last immunization, with titers of 5 × 103 to 8 × 104. B. microti infection rate peaked in mice in both the recombinant protein immunization and the infection control group on day 7 post-immunization, with positive infection rates of 13.3% and 50.0%, and there were significant differences between the two groups in terms of B. microti infection rate on days 3 (χ2= 113.18, P < 0.01), 5 (χ2 = 475.22, P < 0.01), 7 (χ2 = 465.98, P < 0.01) and 9 post-infection (χ2= 18.71, P < 0.01), while the B. microti infection rate tended to be 0 in both groups on day 11 post-immunization. Routine blood tests showed higher red blood cell counts [(5.30 ± 0.50) × 1012 to (9.87 ± 0.24) × 1012 counts/L)] and hemoglobin levels [(89.67 ± 22.80) to (148.60 ± 3.05) g/L)] in the recombinant protein immunization group than in the infection control group on days 0 to 28 post-immunization. Cytometric bead array detected higher serum interferon-γ [(748.59 ± 17.56) to (3 858.28 ± 1 049.10) fg/mL], tumor necrosis factor-α [(6 687.34 ± 1 016.64) to (12 708.13 ± 1 629.79) fg/mL], interleukin (IL)-6 [(611.05 ± 75.60) to (6 852.68 ± 1 554.00) fg/mL] and IL-17a [(167.68 ± 185.00) to (10 849.27 ± 355.40) fg/mL] and lower IL-10 levels [(247.65 ± 138.00) to (18 787.20 ± 2 830.22) fg/mL] in the recombinant protein immunization group than in the infection control group during the study period. Recombinant BmPPIase protein induces up-regulation of interferon-γ, tumor necrosis factor-α and presents a high immunoprotective activity against B. microti infection in mice, which is a potential vaccine candidate protein.