IL-6 In Group Research Articles

Effects of Low and High Doses of Aspirin on Inflammatory Markers in Diabesity Patients: A Quasi-Experimental Study.

Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in mitigating inflammation-related health issues, a key concern in managing diabesity. However, the optimal aspirin dosage and its impact onspecific inflammatory markers, viz. high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, over time remain a subject of ongoing research. Objective This study investigated the effects of different doses of aspirin (150mg and 300mg) on the levels of hs-CRP and IL-6 over a period of 6 months. Methods This cross-sectional observational quasi-experimentstudy involved 125 confirmed type-2 diabetes mellitus (T2DM) patients with obesity aged ≥40 years. Blood samples were collected for analyzing hs-CRP and IL-6 levels. Demographics and clinical characteristics, such as BMI, waist-hip ratio, blood parameters, fasting blood sugar (FBS), and hs-CRP, were analyzed. Results At baseline, both the 150 mg and 300 mg aspirin dose groups had similar median levels of hs-CRP. After two months, there was no significant difference (p=0.150). However, by six months, the 150mg dose group had a significantly higher median hs-CRP than the 300 mg dose group (p=0.003). The 150 mg dose group had a significantly higher median level ofIL-6 levels at baseline (median; 40.0) compared to the 300 mg dose group (median; 2.27, p<0.0001). After two months, thelevels of IL-6in both groups were similar (median; 2.27 and 2.23 respectively, p<0.0001). By the end of six months, the groups had no significant difference (median; 0.53 and 2.22 respectively, p=0.128). Conclusion The dose of aspirin may significantly impact the levels of hs-CRP and IL-6 over time,with the effects being more pronounced after six months of treatment.These findings suggest that aspirin, a commonly used and cost-effective medication, could potentially be leveraged in a more targeted manner to manage inflammation (CRP and IL-6 levels) in individuals with diabesity.

Biomarkers of Orthodontic Patients After Use of 1% Brazilian Red Propolis Toothpaste: A Randomized Clinical Study.

To evaluate the salivary biomarkers and plaque index after a treatment with a propolis-contained toothpaste. This is a longitudinal, randomized, double-blind study where 76 participants were randomized into two groups: Group I: Fluoridated Red Propolis toothpaste; Group II: Fluoridated toothpaste. The participants were selected in a municipality without fluoridated public water. All participants received standardized oral hygiene instructions from the same instructor for 3 daily brushings (after breakfast, after lunch, and before bed) for a period of 2 min; Saliva samples were collected before (D0) and after 28 days (D28) of treatment for analysis of pH and total protein, amylase, and IL-10. Saliva was collected in the initial consultation and on return, totaling two collections. All samples were collected under the same conditions, by the same operator and between 9:00 AM and 11:00 AM in order to minimize the influence of circadian rhythm on salivary flow. On D0 and D28, the various treatments had no effect on total salivary proteins (G1: P = 0.0746; G2: P = 0.2144), and the pH stayed about the same. Additionally, there was no change in the amylase activity in G1 (P = 0.1877) or G2 (P = 0.4674). Significant decreases in G1 (P < 0.0001) and G2 (P = 0.03) were observed with IL-10. There was no statistically significant difference in the salivary flow between the BRP toothpaste-treated group (P = 0.172) and the commercial fluoridated toothpaste-treated group (P = 0.329). Compared to G2 (P = 0.03), G1 showed a superior decline in the plaque index (P = <0.0001). After 28 days of using the toothpastes, there were no changes in the amylase, pH, or total protein indicators. After 28 days, there was a decrease in the propolis group's IL-10 dose and plaque index.

Low-dose IL-2 treatment confers anti-inflammatory effect against subarachnoid hemorrhage in mice

ObjectiveSubarachnoid hemorrhage (SAH) was a stroke with high occurrence and mortality. At the early stage, SAH patients have severe cerebral injury which is contributed by inflammation. In this study, we aimed to explore the anti-inflammation effect of low-dose IL-2 in SAH mice. MethodsThe 12-week-old C57BL/6J male mice were conducted with SAH surgery (Internal carotid artery puncture method). Different dose of IL-2 was injected intraperitoneally for 1 h, 1 day, and 2 days after SAH. Single-cell suspension and flow cytometry were used for the test of regulatory T (Treg) cells. Immunofluorescence staining was used to investigate the phenotypic polarization of microglia and inflammation response around neurons. Enzyme-Linked Immuno-sorbent Assay (ELISA) was applied to detect the level of pro-inflammatory factors. ResultsLow-dose IL-2 could enrich the Treg cells and drive the microglia polarizing to M2. The level of pro-inflammatory factors, IL-1α, IL-6, and TNF-α decreased in the low-dose IL-2 group. The inflammation response around neurons was attenuated. Low-dose IL-2 could increase the number of Treg cells, which could exert a neuroprotective effect against inflammation after SAH. ConclusionLow-dose IL-2 had the potential to be an effective clinical method to inhibit inflammation after SAH.

High-Dimensional Analyses Reveal IL15 Enhances Activation of Sipuleucel-T Lymphocyte Subsets and Reverses Immunoresistance.

Sipuleucel-T (sip-T) is the only FDA-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). To elucidate parameters of the response profile to this therapy, we report high-dimensional analyses of sip-T using cytometry by time of flight (CyTOF) and show a lymphoid predominance, with CD3+ T cells constituting the highest proportion (median ∼60%) of sip-T, followed by B cells, and natural killer (NK) and NKT cells. We hypothesized that treatment of sip-T with homeostatic cytokines known to activate/expand effector lymphocytes could augment efficacy against prostate tumors. Of the cytokines tested, IL15 was the most effective at enhancing activation and proliferation of effector lymphocytes, as well as augmenting tumor cytotoxicity in vitro. Co-culture of sip-T with IL15 and control or prostate-relevant antigens showed substantial activation and expansion of CD8+ T cells and NKT cells in an antigen-specific manner. Adoptive transfer of IL15-treated sip-T into NSG mice resulted in more potent prostate tumor growth inhibition compared with control sip-T. Evaluation of tumor-infiltrating lymphocytes revealed a 2- to 14-fold higher influx of sip-T and a significant increase in IFNγ producing CD8+ T cells and NKT cells within the tumor microenvironment in the IL15 group. In conclusion, we put forward evidence that IL15 treatment can enhance the functional antitumor immunity of sip-T, providing rationale for combining IL15 or IL15 agonists with sip-T to treat patients with mCRPC.

Leaky gut and inflammatory biomarkers in a medication overuse headache model in male rats.

Medication overuse is common among chronic migraine patients and nonsteroidal antiinflammatory drugs (NSAIDs) are the most frequently overused drugs. The pathophysiological mechanisms underlying medication overuse headache (MOH) are not completely understood. Intestinal hyperpermeability and leaky gut are reported in patients using NSAIDs. The aim of the study is to investigate the role of leaky gut and inflammation in an MOH model MOH model in male rats. The study was conducted in male Sprague Dawley rats. There were two experimental groups. The first group was the chronic NSAID group in which the rats received mefenamic acid (n = 8) for four weeks intraperitoneally (ip) and the second group was the vehicle group (n = 8) that received 5% dimethyl sulfoxide+sesame oil (ip) for 4 weeks. We assessed spontaneous pain-like behavior, periorbital mechanical withdrawal thresholds, and anxiety-like behavior using an elevated plus maze test. After behavioral testing, serum levels of occludin and lipopolysaccharide-binding protein (LBP) and brain levels of IL-17, IL-6, and high mobility group box 1 protein (HMGB1) were evaluated with ELISA.Results: Serum LBP and occludin levels and brain IL-17 and HMGB1 levels were significantly elevated in the chronic NSAID group compared to its vehicle (p = 0.006, p = 0.016, p = 0.016 and p = 0.016 respectively) while brain IL-6 levels were comparable (p = 0.67) between the groups. The chronic NSAID group showed pain-like and anxiety-like behavior in behavioral tests. Brain IL-17 level was positively correlated with number of head shakes (r = 0.64, p = 0.045), brain IL-6 level was negatively correlated with periorbital mechanical withdrawal thresholds (r = -0.71, p = 0.049), and serum occludin level was positively correlated with grooming duration (r = 0.73, p = 0.032) in chronic NSAID group. Elevated serum occludin and LBP levels and brain IL-17 and HMGB1 levels indicate a possible role of leaky gut and inflammation in an MOH model in male rats. Additionally, a significant correlation between pain behavior and markers of inflammation and intestinal hyperpermeability, supports the role of inflammation and leaky gut in MOH pathophysiology.

Staphylococcus aureus lysate induces an IgE response via memory B cells in nasal polyps

Locally increased IgE levels plays a pathologic role in chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to investigate whether Staphylococcus aureus could induce aberrant IgE synthesis in CRSwNP and the potential mechanisms involved. Total IgE, IL-4, IL-5, and IL-13 concentrations in the supernatants of the cultures stimulated with S aureus lysate were assessed by ELISA. S aureus-induced cellular responses were investigated by single-cell RNA sequencing. Flow cytometry and quantitative reverse transcription PCR were used to analyze B-cell subsets and stimulated cell ε-germline transcript expression, respectively. IgE-positive B-cell and germinal center localization were assessed by immunohistochemistry and immunofluorescence. S aureus lysate induced IgE production in the supernatants of nasal polyp (NP) tissues but not in those of healthy nasal mucosa. Moreover, IgE levels increased from days 2 to 4 after stimulation, paralleling the enhanced ε-germline transcript, IL-5, and IL-13 expression. Single-cell RNA sequencing revealed that there were increased IL-5 and IL-13 in group 2 innate lymphoid cells and identified a clonal overlap between unstimulated memory B cells and S aureus-stimulated plasma cells. The enriched IgE within NPs was mainly produced by IgE-negative memory B cells. Cellular evidence indicated that the IgE memory response to S aureus might also exist in the peripheral blood of CRSwNP patients. The S aureus-induced IgE memory response was associated with elevated IgE levels in NPs, asthma, and postoperative CRSwNP recurrence. S aureus induced an IgE response via IgE-negative memory B cells in CRSwNP patients, possibly contributing to CRSwNP development.

Effects of acupuncture on RT-BM1 and maternal-fetal immune tolerance in rats with ovarian hyperstimulation: 针刺对超排卵大鼠RT-BM1及母胎免疫耐受的影响

ObjectiveThis study aimed to evaluate the effects of acupuncture on embryo implantation and maternal–fetal immune tolerance in rats with ovarian hyperstimulation, identify the mechanisms of acupuncture treatment, and promote application of acupuncture in the field of assisted reproduction. MethodsEighty female Wistar rats were randomized into normal (N), model (M), acupuncture treatment (A), and progesterone treatment (P) groups, with 20 rats in each group. An ovarian hyperstimulation model was established in groups M, A, and P by the peritoneal injection of pregnant mare serum gonadotropin (PMSG) combined with human chorionic gonadotropin (HCG). Bilateral “Sanyinjiao (SP6)”, “Zusanli (ST36)” and “Taichong (LR3)” as acupoints were needled in rats in group A. Rats in group P received an intramuscular injection of progesterone (4 mg/kg). All pregnant rats were treated for seven days. On the 8th day, the pregnant rats were sacrificed for testing. The expression levels of estrogen (E2) and progesterone (P4) in serum and their receptors in the endometrium, Th1 and Th2 cytokines in serum and endometrium, RT-BM1 (the counterpart of HLA-G in rats) mRNA, Ly49 activating receptors (Ly49s3, Ly49s5) and inhibitory receptors (Ly49i3, Ly49i4, Ly49i5) on immunocytes in the maternal–fetal interface were detected using ELISA, Western blot, and real-time polymerase chain reaction (PCR). ResultsCompared with group N, the pregnancy rate and the number of implanted embryos were significantly decreased in group M (P < 0.05); E2 and P4 levels in serum, and the protein levels of ER-α and Progesterone Receptor (PGR) in the implantation site of endometrial tissue were significantly reduced in group M (P < 0.05); the expression of INF-γ and IL-2 in serum and endometrium were significantly increased, while the expression of IL-4, IL-6, and IL-10 in serum and endometrium were significantly decreased in group M(P < 0.05). The mRNA levels of RT-BM1, Ly49i3, and Ly49i4 receptors in group M were significantly higher than those in group N, whereas the mRNA levels of Ly49i5 and Ly49s5 receptors in group M were significantly lower than those in group N at the maternal–fetal interface (P < 0.05). The pregnancy rate and number of implanted embryos were significantly higher in group A than in group M (P < 0.05). Serum E2 and P4 levels were significantly higher in groups A and P than in group M (P < 0.05). The expression of ER-α and PGR in the implantation site of endometrial tissue in group A were significantly higher than those in group M (P < 0.05). The serum levels of INF-γ and IL-2 in group A and group P were significantly lower than those in group M (P < 0.05). The serum expression of IL-4, IL-6, IL-10 in group A and group P were significantly higher than those in group M (P < 0.05). The endometrium expression of INF-γ and IL-2 in group A were significantly lower than those in group M (P < 0.05). The endometrium expression of IL-4, IL-6, IL-10 in group A were significantly higher than those in group M (P < 0.05). The endometrium expression of INF-γ in group P were significantly lower than those in group M (P < 0.05). The endometrium expression of IL-6 and IL-10 in group P were significantly higher than those in group M (P < 0.05). The mRNA levels of RT-BM1 and these Ly49 receptors (except the Ly49s3 receptor) at the maternal–fetal interface of groups A and P were higher than those of group M (P < 0.05). ConclusionAcupuncture can significantly increase the pregnancy rate and average number of implanted blastocysts in rats with ovarian hyperstimulation. This mechanism is related to the effects of acupuncture in upregulating the expression of RT-BM1, regulating the balance of Th1/Th2 cytokines, and upregulating the expression of inhibitory receptors in immunocytes.

Hsa-miR-301a-3p inhibited the killing effect of natural killer cells on non-small cell lung cancer cells by regulating RUNX3.

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. Natural killer (NK) cell-based immunotherapy is a promising anti-tumor strategy in various cancers including NSCLC. We aimed to investigate the specific mechanisms that regulate the killing effect of NK cells to NSCLC cells. Reverse transcription-quantitative PCR (RT-qPCR) assay was applied to measure the levels of hsa-microRNA (miR)-301a-3p and Runt-related transcription factor 3 (RUNX3). Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of IFN-γ and TNF-α. Lactate dehydrogenase assay was applied to detect the killing effect of NK cells. Dualluciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to confirm the regulatory relationship between hsa-miR-301a-3p and RUNX3. A low expression of hsa-miR-301a-3p was observed in NK cells stimulated by IL-2. The levels of IFN-γ and TNF-α were increased in NK cells of the IL-2 group. Overexpression of hsa-miR-301a-3p reduced the levels of IFN-γ and TNF-α as well as the killing effect of NK cells. Furthermore, RUNX3 was identified to be a target of hsamiR-301a-3p. hsa-miR-301a-3p suppressed the cytotoxicity of NK cells to NSCLC cells by inhibiting the expression of RUNX3. We found hsa-miR-301a-3p promoted tumor growth by suppressing the killing effect of NK cells against NSCLC cells in vivo. Hsa-miR-301a-3p suppressed the killing effect of NK cells on NSCLC cells by targeting RUNX3, which may provide promising strategies for NK cell-based antitumor therapies.

Differential expression of IFN-α, IL-12 and BAFF on renal immune cells and its relevance to disease activity and treatment responsiveness in patients with proliferative lupus nephritis

ObjectiveSince molecularly targeted therapies are emerging for treating lupus nephritis (LN), this study aimed to assess the immunohistochemical findings of the cytokines in renal tissue and their pathological and clinical...

Comparison between levels of Homocysteine, Interleukin-6 and Interleukin-10 in severe cases of Egyptian COVID-19 patients

Coronavirus disease 2019 (COVID-19) is the reason of an outbreak of respiratory illnesses ranging from typical cold to severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome. We intended to compare levels of IL-6, IL-10, and homocysteine in the sera of severe COVID-19 Egyptian patients and connect them with the extent of the illness. This cross-sectional study included 90 COVID-19 Egyptian patients. They included 45 non severe cases (group 1) and 45 severe cases (group 2). There was statistically significantly increase in IL-6 in group 2 (median = 7.05, IQR = 6.2 – 7.9; p&lt;0.001) in comparison to group 1 (median = 4.96, IQR = 4.5 – 5.8) and statistically significantly increase in IL-10 in group 2 (154.1 ± 73.3) in comparison to group 1 (47.04 ± 23.8; p&lt;0.001). There were no variations in the examined groups’ homocysteine levels (p= 0.318). Furthermore, there was statistically substantial positive connection (r=0.30) between IL-6 and AST (p=0.046) and between IL-10 and HCT (r = 0.37, p=0.012). In addition, data of other studied parameters are presented. In conclusion, IL-6 and IL-10 could be proposed for follow up of COVID-19 patients and to detect cases before progressing to a severe disease stage.

Can M-30, M-65, and IL-6 serum levels be useful markers in the diagnosis of preeclampsia and gestational diabetes?

We aimed to evaluate the maternal and fetal serum M-30, M-65 and IL-6 levels in preeclampsia and gestational diabetes mellitus (GDM) in both maternal and cord blood. Women with preeclampsia (n=30), GDM (n=30), and uncomplicated pregnancy (n=28) were evaluated in a cross-sectional study. After clamping during delivery, the serum M-30, M-65, and IL-6 levels were measured in both maternal venous blood and cord blood. The serum M-30, M-65, and IL-6 levels were significantly higher in preeclampsia and GDM patients' maternal blood and cord blood samples compared to the control group. In the preeclampsia group, M-65 was significantly higher in cord blood compared with the level in maternal serum, but there was no significant difference between the GDM and control groups. The control group's IL-6 level in cord blood was statistically significantly lower than the other groups. Although the M-30 value in both maternal and cord blood was statistically lower in the control group than in the GDM group, there was no significant difference between the two groups when compared to the preeclampsia group. M-30 and M-65 molecules appear to have the potential to serve as biochemical markers in placental diseases, particularly preeclampsia and gestational diabetes. Due to the insufficient sample sizes, more research is needed.

Effect of recombinant human thrombopoietin on IL-2, IL-4 and platelet parameters in thrombocytopenic purpura.

The objective of this study was to observe the effect of recombinant human thrombopoietin on IL-2, IL-4 and platelet parameters in thrombocytopenic purpura. For this purpose, a convenient sampling method was used to select 84 patients with thrombocytopenic purpura who visited the hospital from January 2018 to December 2022. The patients were divided into the norm group and rhTPO group with 42 cases each by random number table. The norm group was treated with routine treatment, while the rhTPO group was treated with recombinant thrombopoietin based on routine treatment. The changes in IL-2, IL-4, platelet parameters, immune recovery and treatment efficiency of the two groups were compared before and after treatment. Findings suggested that the levels of IL-2 and IL-4 in both groups decreased after treatment compared with those before treatment. However, the level of IL-2 in the rhTPO group after treatment was lower than that in the norm group, and the level of IL-4 in the rhTPO group after treatment was higher than that in the norm group (P<0.05). The levels of platelet parameters PLT and PCT in the two groups after treatment were higher than those before treatment, but the levels of PLT and PCT in the rhTPO group after treatment were higher than those in the norm group (P<0.05). The PLT of the rhTPO group was (69.57±6.73)×109/L after 7 days of treatment, which was higher than that in the norm group (62.05 ± 8.52)×109/L (P<0.05). The levels of PDW and MPV in the two groups after treatment decreased compared with those before treatment, but the levels of PDW and MPV in the rhTPO group after treatment were lower than those in the norm group (P<0.05). The overall immune recovery and treatment effectiveness of the rhTPO group were significantly better than those of the norm group. In summary, recombinant human thrombopoietin used in patients with thrombocytopenic purpura can maintain the balance between T cell activation and inhibition homeostasis, and promote faster recovery of platelet parameters.

Some features of the immune system response in the new coronavirus infection COVID-19

AIM: to study the cytokine link of immunity in patients with the new coronavirus infection COVID-19 and the possibility of using these data to predict the risk of lung tissue damage. MATERIALS AND METHODS: Patients with diagnosed new coronavirus infection COVID-19 were divided into 4 groups depending on the severity of the disease: 1 — asymptomatic patients; 2 — patients with lung tissue damage in the amount of 25%; 3 — patients with lung tissue damage 50%; 4 — patients with lung tissue damage 75% (according to the results computed tomography). Immunological studies were performed upon admission to the clinic, then after 7 days and before discharge. The concentration of cytokines in blood serum was studied by the method of solid-phase enzyme immunoassay using kits manufactured by Vector Best. RESULTS: In all groups, a low content of proinflammatory cytokines was found: tumor necrosis factor and interferon-γ, interleukin-1, interleukin-2. The median level of interleukin-6 in all groups during the entire follow-up period was within the normal range, however, in some patients there was a multiple excess of its concentration. In groups with 50% and 75% lung tissue damage, an increase in the concentration of interleukin-8 was shown. Statistically significant differences were noted only for the level of interleukin-8 between the group with an asymptomatic form of infection and the CT-2 and CT-3 groups. It was found that the concentration of interleukin-1 below 3.58 pg/ml is a significant risk factor for severe disease. In all groups of subjects, low levels of interleukin-4 and interleukin-10 were noted, while there was no significant difference between the groups. Positive correlations were revealed between the degree of lung tissue damage and the level of interleukins 6, 2 and 8. Negative correlations were established between the degree of lung tissue damage and the content of interleukin-1. CONCLUSION: There was no significant activation of the cytokine link of adaptive antiviral immunity in the examined contingent. Serum cytokine levels were within normal values and had no significant intergroup differences. An increase in IL-8 in groups with clinically pronounced signs of infection indicates the activation of indicators characterizing innate immunity.

Evaluation of the Local Immune Response to Hydatid Cysts in Sheep Liver.

In order to characterize the inflammatory phenotype of livers of sheep naturally infected by cystic echinococcosis, 100 sheep livers have been macroscopically assessed for the presence of hydatid cysts and sampled for histopathological and molecular analysis. According to gross and microscopic examination, livers were subsequently classified into three groups: normal liver (Group A), liver with the presence of fertile hydatid cysts (Group B), and liver with the presence of sterile hydatid cysts (Group C). Immunohistochemical analyses were accomplished using primary antibodies anti-Iba1, anti-CD3, anti-CD20, anti-TGF-β, and anti-MMP9. Finally, real-time PCR was performed in order to estimate the concentration levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin (IL)-12, IL-10, and TGF-β. Immunohistochemical analysis showed a diffuse immunolabelling of mononuclear cells for Iba-1 and TGF-β and a higher amount of CD20+ B cells compared to CD3+ T cells in both Groups B and C. The expression levels of Th-1-like immune cytokines TNF-α, INF-γ, and IL-12 did not show significant statistical differences. However, we found a significant increase in expression levels of Th-2 immune cytokines TGF-β and IL-10 in Groups B and C compared to Group A. Taken together, our findings suggest that macrophages have a predominant role in the local immune response to cystic echinococcosis. Moreover, we can speculate that Th2 immunity may be dominant, corroborating the idea that B cells are decisively essential in the control of the immune response during parasitic infection and that the immunomodulatory role of IL-10 and TGF-β may ensure the persistence of the parasite within the host.

In vivo anti-inflammatory effects of anti-toxic principles from Moringa oleifera(MO11) and Musa sapientum (MS06) via NF-KB/IL-4/IL-10- mediated pathway in Cadmium Chloride-induced hepato-toxicity.

Cadmium-induction of hepato-toxicity and inflammation in animal models have been reported. The mechanism underlying hepatic inflammation is poorly understood. This study evaluated antiinflammatory potentials of MO11 (isolated from Moringa oleifera leaves) and MS06 (isolated from Musa sapientum suckers) in Cadmium Chloride (CdCl)-induced hepato-toxicity and inflammation in rats.Twenty-eight adult male wistar rats (average weight of 155 g) were randomly divided into 7 groups (n = 4). Group 1 was control. Groups 2 - 4 and 7 received single intraperitoneal administration of 1.5 mg/Kg bodyweight of CdCl on Day 1. Thereafter, Groups 3, 4 and 7 were post-treated with 15 mg/Kg bodyweight of MO11, 15 mg/Kg bodyweight of MO11 + 7 mg/Kg bodyweight of MS06 and single-dose of 3.35 mg/Kg bodyweight of Doxorubicin respectively (Days 1 - 17). Groups 5 and 6 received only MO11-dose and Olive Oil (vehicle) respectively (Days 1 - 17). Liver histopathology (Heamatoxyline and Eosin technique) and ELISA concentrations of proinflammatory biomarkers (IL-1β, IL-6, IL-8 and NF-kB) and anti-inflammatory biomarkers (IL-4 and IL-10) in liver homogenates of rats of Groups 1 - 7 were evaluated. Computed data were statistically analysed using Mann-Whitney-U test at P ≤ 0.05. Histo-pathological analyses showed normal liver histology in Groups 1 - 7. Post-treatments of CdCl-induced hepato-toxicity and hepatic inflammation with MO11 and MO11+MS06 resulted in downregulations of IL-1β, IL-6, IL- 8 and NF-kB, but upregulations of IL-4 and IL-10 in Groups 3, 4 and 7, compared with Group 2. MO11 and MS06 possess hepato-protective and anti-inflammatory potentials.

Cadmium Chloride-induced skin ulceration and inflammation in rats: Anti-inflammatory potentials of Moringa oleifera and Musa sapientium via NF-KB/IL-4/1L-10-mediated pathway.

Cadmium-induced toxicity resulted in skin carcinogenesis in rats. The mechanism underlying Cadmium-induced skin carcinogenesis remains poorly understood. Therefore, we evaluated anticancer potentials of Moringa oleifera and Musa sapientum in Cadmium Chloride (CdCl2)-induced skin carcinogenesis, ulceration and inflammation in rats. Twenty-eight adult male wistar rats (average weight of 155 g) were randomly divided into 7 groups (n = 4). Group 1 was control. Groups 2-4 and 7 received single intraperitoneal administration of 1.5 mg/Kg bodyweight of CdCl on Day 1. Thereafter, Groups 3, 4 and 7 were post-treated with 15 mg/Kg bodyweight of MO11, 15 mg/Kg bodyweight of MO11 + 7 mg/Kg bodyweight of MS06 and 3.35 mg/Kg bodyweight of Doxorubicin respectively (Days 1-17). Groups 5 and 6 received only MO11-dose and Olive Oil (vehicle) respectively (Days 1-17). Skin histopathology (Heamatoxyline and Eosin technique) and ELISA concentrations of pro-inflammatory biomarkers (IL-1β, IL-6, IL-8 and NF-kB) and antiinflammatory biomarkers (IL-4 and IL-10) in liver homogenates of rats of Groups 1-7 were evaluated. Computed data were statistically analysed using Mann-Whitney-U test at P ≤ 0.05. Histo-pathological evaluations showed normal skin histology in Groups 1 and 3-5, but skin histoalterations in Groups 2 and 6. Post-treatments of CdCl2-induced skin carcinogenesis with MO11, MO11+MS06 and Doxorubicin resulted in downregulations of IL-1β, IL-6, IL-8 and NF-kB, butupregulations of IL-4 and IL-10 in Groups 3, 4 and 6, compared with Group 2. MO11 and MO11+MS06 achieved better anti-inflammatory potentials than Doxorubicin. Overall, MO11 and MS06 possess anticancer and anti-inflammatory potentials.

In vitro evaluation of ginsenoside Rg1 immunostimulating effect in bovine mononuclear cells

The aim of this study was to evaluate the immunomodulatory effect of ginsenoside Rg1 on mammary secretion and peripheral blood mononuclear cells (MSMC and PBMC, respectively). The mRNA expression of TLR2, TLR4 and selected cytokines were evaluated on MSMC after Rg1 treatment. Also, TLR2 and TLR4 protein expression was evaluated on MSMC and PBMC after Rg1 treatment. Phagocytic activity and capacity, ROS production and MHC-II expression were evaluated on MSMC and PBMC after Rg1 treatment and co-culture with Staphylococcus aureus strain 5011. Rg1 induced mRNA expression of TLR2, TLR4, TNF-α, IL-1β, IL-6 and IL-8 in groups treated with different concentrations and at different times in MSMC, and induced TLR2 and TLR4 protein expression in MSMC and PBMC. Rg1 increased phagocytic capacity and ROS production in MSMC and PBMC. Rg1 increased MHC-II expression by PBMC. However, Rg1 pre-treatment had no effect on cells co-cultured with S. aureus. In conclusion, Rg1 was able to stimulate several sensing and effector activities in these immune cells.

Multi-omics analysis of the effects of dietary changes and probiotics on diet-induced obesity

The consumption of a healthy diet is critical for maintaining and promoting human health. In the context of the rapid transformation from a high-fat diet (HFD) to a Mediterranean diet (MD) leading to major systemic changes, we explored the necessity of a transitional standard diet (TSD) between these two varied diets and the adjuvant effect of probiotics. HFD-fed mice were used for studying the changes and benefits of a dietary intervention and probiotic treatment. By measuring multiple systemic alterations such as weight (group B vs. group E, P < 0.05), liver function (AST, group C vs. group E, P < 0.001), and histopathology, we found that an MD, TSD and Bifidobacterium longum all contribute to alleviating lipid deposition and liver injury. The downregulation of IL-17 (group B vs. group E, P < 0.01) and MIP-1α (group B vs. group E, P < 0.001) also demonstrated the anti-inflammatory effects of the TSD. Moreover, we performed multi-omics analysis combined with the 16S sequencing, transcriptome and metabolome results and found that the TSD increased the abundance of the Lactobacillus genus (group C vs. group E, P < 0.01) and effectively lowered lipid accumulation and systemic inflammation. Furthermore, B. longum played an important role in the synergistic effect. The results showed that a TSD might be useful for HFD-induced obesity before drastic dietary changes, and probiotics were also beneficial.

Evaluating the effects of curcumin nanomicelles on clinical outcome and cellular immune responses in critically ill sepsis patients: A randomized, double-blind, and placebo-controlled trial.

In sepsis, the immune system is overreacting to infection, leading to organ dysfunction and death. The purpose of this study was to investigate the impacts of curcumin nanomicelles on clinical outcomes and cellular immune responses in critically ill sepsis patients. For 10 days, 40 patients in the intensive care units (ICU) were randomized between the nano curcumin (NC) and placebo groups in a randomized study. We evaluated serum levels of biochemical factors, inflammatory biomarkers, the mRNA expression levels of FOXP3, NLRP-3, IFN-γ, and NF-κp genes in the PBMCs, and clinical outcomes before the beginning of the supplementation and on days 5 and 10. NLR family pyrin domain containing 3 (NLRP3), interferon gamma (IFN-γ), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels significantly P = 0.014, P = 0.014, and P = 0.019, respectively) decreased, but forkhead box P3 (FOXP3) mRNA expression levels increased significantly (P = 0.008) in the NC group compared to the placebo group after 10 days. NC supplementation decreased serum levels of IL-22, IL-17, and high mobility group box 1 (HMGB1) (P < 0.05). Nevertheless, biochemical factors and nutritional status did not differ significantly (P > 0.05). NC supplementation resulted in decreased sequential organ failure assessment and multiple organ dysfunction syndromes scores, while it did not have significant impacts on length of stay in the ICU, systolic blood pressure, diastolic blood pressure, a saturation of oxygen (%), and respiratory rate (breaths/min) PaO2/FiO2 (p > 0.05). For critically ill patients with sepsis, NC supplementation may be an effective therapeutic strategy. More randomized clinical trials involving longer follow-up periods and different doses are needed to achieve the best results.

Absolute decrease in regulatory T cells and low-dose interleukin-2 therapy: restoring and expanding regulatory T cells to treat systemic sclerosis: a 24-week study.

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular lesions, immunological alterations and tissue fibrosis. There is some evidence of an imbalance between T-cell subsets in this disease. Interleukin (IL)-2 is a cytokine that can regulate the activity of immune cells and there is evidence that low-dose IL-2 therapy can be used to treat immune diseases. To investigate the changes of peripheral lymphocyte subsets, especially T helper (Th)17 and regulatory T (Treg) cells and the effects of low-dose IL-2 therapy in patients with SSc. In total, 66 patients with SSc and 49 sex- and age-matched healthy controls (HCs), were enrolled. The absolute numbers of peripheral lymphocyte subsets in these individuals were determined by flow cytometry. The 66 patients, were divided into 2 groups: 23 (the IL-2 group) were treated with low-dose (5.0 × 105 IU) IL-2 by subcutaneous injection daily for 5 days combined with conventional therapy, while the remaining 23 patients received conventional therapy only. Compared with HCs, the absolute numbers of peripheral T, CD4+ T, CD8+ T, natural killer and Treg cells were significantly lower in patients with SSc, with the most dramatic difference seen in both the absolute number and percentage of Treg cells in these patients, including new (previously untreated) cases, resulting in an imbalance (elevated ratio) between Th17 and Treg cells. At Week 24 after commencement of IL-2 treatment, Treg cells were markedly increased and tended to restore the balance of Th17 to Treg cells compared with baseline. Erythrocyte sedimentation rate, C-reactive protein, modified Rodnan Skin Score and visual analogue scale score were significantly decreased in both the IL-2 and non-IL-2 groups, indicating disease improvement. Notably, compared with those in the non-IL-2 group, patients treated with IL-2 had greater improvement. Our study showed that the absolute numbers of peripheral Treg cells together with total T, CD4+ T, CD8+ T and NK is significantly decreased, leading to an imbalance of Th17 to Treg cells in patients with SSc, and that low-dose IL-2 treatment could restore the balance of the two immune cells and reduce disease activity without obvious adverse effects.