Decreased IL-6 Levels Research Articles

Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model.

The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. β-caryophyllene is a sesquiterpene in Copaifera langsdorffii oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with C. langsdorffii, β-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male Wistar rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the β-caryophyllene-treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with β-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the β-caryophyllene-treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1β and IL-6. After β-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-γ2 and desmoglein-3 immunolabeling. β-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson's trichrome staining. These findings indicated the wound-healing potential of β-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms.

Combination of Sleeve Gastrectomy and Mesenchymal Stem Cells Improves Insulin Resistance by Modulating Pro-inflammatory Milieu in Obese Type 2 Diabetic Rat Model

ABSTRACT Background: Obesity is a major risk factor for the onset of insulin resistance and type 2 diabetes mellitus (T2DM) caused by chronic inflammation of the islets of langerhans. Sleeve gastrectomy (SG) procedure increases particular hormone which stimulates insulin sensitivity. Mesenchymal stem cells (MSCs) can also exhibit potential immunomodulatory properties through their paracrine effects, however the mechanism regarding combination of them could not be adequately explained. Aim: In this study, we explore the potential of sleeve gastrectomy followed by injection of MSCs in type 2 diabetic rats with obesity in improving insulin resistance. Methods: This study used a pre and post control group design with 18 rats that divided into 3 groups: control (C), sleeve gastrectomy (SG), sleeve gastrectomy + MSCs (SG+M). On day 10, the level of IL-6, IL-10 and HOMA-IR were evaluated using ELISA. Results: This study showed a significant decrease of IL-6 level in all treatment groups on day 10, in which SG+M group showed optimum inhibition. This result was in line with the optimum increase of IL-10 in SG+M group. Moreover, our study also revealed the optimum decrease of HOMA-IR in SG+M group on day 10. Conclusion: Combination of SG and MSCs can optimally improve insulin resistance by modulating proinflammatory milieu though inhibiting IL-6 level and upregulating IL-10 level in obese type 2 diabetes mellitus rat model.

Impact of Pulmonary Rehabilitation on Hospitalization Duration, IL-6 Levels, and Respiratory Muscle Power in Hospitalized Community-Acquired Pneumonia Patients

Background: Pneumonia is acute inflammation of the lung parenchyma. The long duration of hospitalization is associated with increased morbidity, nosocomial infections and treatment costs. Methods: The study was conducted from May to November 2019 at Saiful Anwar Hospital, Malang, with 40 pneumonia patients in the non-intensive community inpatient room divided into 2 groups. The treatment group performed pulmonary rehabilitation measures consisting of breathing exercise, effective coughing techniques, clapping, postural drainage and respiratory muscle training using spirometry incentives. Results: The duration of hospitalization for the treatment group was 2.25 days shorter (p<0.001). The average IL-6 level in the 5th day of the treatment group was lower than without treatment, that was 54.43 pg/ml (p=0.221). The mean of pressure threshold loading in the group without treatment was 31.5 cmH2O on first day and 36.35 cmH2O on the 5th day (p <0.001) and on first day treatment group was 32.9 cmH2O and 39.35 cmH2O on the 5th day (p=0.001), and the mean value of the 5th day of the treatment group was higher than without treatment (P=0.015). the mean of the 5th day of the treatment group was higher than without treatment (p=0.06).Conclusion: Pulmonary rehabilitation as adjunctive therapy shortens the duration of hospitalization. In both groups there was a decrease in IL-6 levels on the 5th day compared to zero and the lower IL-6 levels were not significant in the treatment group. There was a significant increase in the value of pressure threshold loading inspiration and expiration day fivecompared to day zero in the two groups and there was a significant increase in the Pressure Threshold Loading Inspiration mean treatment group compared to no treatment on the 5th day, but the Pressure Threshold Loading Expiration rate showed no significant increase.

The Role of FXR-Signaling Variability in the Development and Course of Non-Alcoholic Fatty Liver Disease in Children

Genetic mechanisms among many other factors play a crucial role in the development and progression of nonalcoholic fatty liver disease (NAFLD). The farnesoid X-receptor (FXR) regulates the expression of target genes involved in metabolic and energy homeostasis, so it can be assumed that genetic variations within the NR1H4 gene, encoding FXR, can affect the development or progression of associated diseases, including NAFLD. To study the association of SNP rs11110390 NR1H4 gene with the probability of development and course of NAFLD in children. 76 children aged 9-17 years and overweight were examined. According to controlled attenuated parameter (CAP) measurement (Fibroscan®502touch) children were divided into 2 groups: group 1 consisted of 40 patients with NAFLD, group 2 was composed by 36 patients without hepatic steatosis. According to genetic testing children were divided into 3 subgroups - children with CC-, CT-, TT-genotype SNP rs11110390 NR1H4 gene. The frequency of TT-genotype SNP rs11110390 NR1H4 gene detection in children with NAFLD was 17.5% versus 2.8% in the control group (p NR1H4 gene the liver stiffness (p NR1H4 (p NR1H4 is associated with an increased probability of NAFLD development in children. An increase in the steatosis degree and liver stiffness in combination with increased taurine-conjugated bile acids fractions in the hepatic and gallbladder's bile, shift in cytokine balance due to a decrease in IL-10 level in children with TT-genotype SNP rs11110390 NR1H4 were observed.

Exploring the Therapeutic Mechanism of Tingli Dazao Xiefei Decoction on Heart Failure Based on Network Pharmacology and Experimental Study

Background Tingli Dazao Xiefei decoction (TDXD) has been shown to have a therapeutic effect on heart failure (HF). Nevertheless, its molecular mechanism for treating HF is still unclear. Materials and Methods TDXD and HF targets were collected from the databases, and protein-protein interaction (PPI) analysis and enrichment analysis were performed on the overlapping targets. Then, AutoDock was employed for molecular docking. Finally, we used the left anterior descending coronary artery (LAD) ligation to induce HF model rats for in vivo experiments and verified the effect and mechanism of TDXD on HF. Results Network pharmacological analysis showed that the main active components of TDXD in treating HF were quercetin, kaempferol, beta-carotene, isorhamnetin, and beta-sitosterol, and the core targets were IL-6, VEGFA, TNF, AKT1, and MAPK1. Multiple gene functions and signaling pathways were obtained by enrichment analysis, among which inflammation-related, PI3K/Akt, and MAPK signaling pathways were closely related to HF. Furthermore, the molecular docking results showed that the core targets had good binding ability with the main active components. Animal experiments showed that TDXD could effectively improve left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS), decrease left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs), reduce the area of myocardial fibrosis, and decrease serum BNP, LDH, CK-MB, IL-6, IL-1β, and TNF-α levels in HF rats. Meanwhile, TDXD could upregulate the expression of Bcl-2, downregulate the expression of Bax, and reduce cardiomyocyte apoptosis. At the same time, it was verified that TDXD could significantly decrease the expression of PI3K, P-Akt, and P-MAPK. Captopril showed similar effects. Conclusions Combining network pharmacological analysis and experimental validation, this study verified that TDXD could improve cardiac function and protect against cardiac injury by inhibiting the activation of PI3K/Akt and MAPK signaling pathways.

Congenital transmission of Mexican strains of Trypanosoma cruzi TcIa: interaction between parasite and human placental explants.

Congenital transmission of Chagas disease plays an important role in endemic countries because it is not a diagnosis that is encountered frequently in prenatal care. Due to limited information regarding congenital transmission of Trypanosoma cruzi in Mexico, the present study aimed to investigate protozoan infectivity and modulation of immune responses in human placental explants infected with T. cruzi Ia Mexican strains. The Inc-5 strain showed increased infectivity and modulated IL-1β, IL-10 and TLR-4, decreasing their expression after 24 h of infection. Both strains (Inc-5 and Ninoa) stimulated the production of TNF-α and decreased IL-6 levels 96 h after infection. An important detachment of the syncytiotrophoblast caused by infection with T. cruzi was observed after 24 h of infection. In this study, ex vivo infection of human placental villi was performed to better understand interactions involving parasitic T. cruzi and human placental tissue. It was concluded that the strains of TcIa present parasitism in placental tissue, modulation of the innate immune system of the placenta, and cause intense detachment of the syncytiotrophoblast, a fact that may be more associated with abortion and premature birth events than the congenital transmission itself, justifying the low rate of this transmission mechanism by this genotype.

CHANGES IN THE ACTIVITY OF INDUCIBLE NO-SYNTHASE AND ARGINASE, THEIR RELATIONSHIP WITH THE LEVEL OF PRO- AND ANTI-INFLAMMATORY CYTOKINES IN CERVICAL MUCUS IN PREGNANT WOMEN, WHO UNDERWENT IVF AND ARE AT RISK OF PRETERM CHILDBIRTH

Introduction. Nitric oxide (NO) produces a wide range of bioregulatory effects. Imbalance in the ratio of the activity of inducible NO-synthase and arginase in favor of iNOS can lead to a pro-inflammatory reaction. At the risk of preterm childbirth, the content of proinflammatory cytokines increases both at the local and systemic levels. The aim of this work is to study the relationship between changes in the content of pro- and anti-inflammatory cytokines and the activity of inducible NO-synthase and arginase in the cervical mucus of women with in vitro fertilization (IVF), who are at risk of preterm childbirth. Materials and methods. The test group (TG) included 37 women, who underwent IVF and presented prognostic signs, indicating a high risk of preterm birth in the future. The control group (CP) consisted of 20 healthy pregnant women, who did not undergo assisted reproductive technologies. We determined the indicators of inducible NO-synthase activity and total arginase activity, as well as the level of pro- and anti-inflammatory cytokines in the mucus of the cervical canal of the participants at their 28-34 weeks of pregnancy. Results and discussion. The activity of iNOS in TG significantly increased (in 2.57 times) compared to healthy pregnant women (CP), while the activity of arginase, on the contrary, decreased significantly (in 1.91 times). There was a significant increase in the levels of pro-inflammatory cytokines INF-γ and TNF-α in the TG women, while they demonstrated the significantly reduced concentration of anti-inflammatory cytokine IL-10. In cervical mucus taken from TG women, positive correlations were found between an increase in the concentration of the proinflammatory cytokine INF-γ and an increase in iNOS activity, between a decrease in IL-10 levels and arginase activity, and a negative relationship between an increase in iNOS activity and a decrease in arginase activity. Conclusions. The detected cytokine imbalance in pregnant women, who underwent in vitro fertilization and were at risk of preterm childbirth, together with a impaired ratio of iNOS and arginase, indicates an inappropriate level of immunosuppression. These immune changes, by activating cellular responses of maternal immunity, can contribute to preterme childbirth.

Abstract 13663: Safety and Possible Effectiveness of Paclitaxel Associated to LDL-Like Nanoparticles (LDE) in the Treatment of Patients With Chronic Ischemic Heart Disease

Introduction: Experimental studies have shown that anti-proliferative chemotherapeutic agents such as paclitaxel (PTX), associated to solid lipid nanoparticles (LDE), have marked anti-atherosclerotic effects. The combination with LDE nearly abolishes PTX toxicity. Hypothesis: Treatment with LDE-PTX in patients with chronic ischemic heart disease (CIHD) is tolerable and safe, and favorably changes plaque characteristics, as denoted by coronary computerized tomography angiography (CCTA). Methods: In this prospective, randomized, double-blind, placebo-controlled study, patients with multivessel CIHD received IV infusions of either LDE-PTX (n=20; PTX dose: 175 mg/m2 body surface) or LDE alone (n=20; placebo group). Infusions were administered every 3 weeks for 6 times. Analysis of cardiovascular risk and inflammatory biomarkers and CCTA data was performed at baseline and at the end of the study. Clinical and laboratorial safety evaluations were made before each infusion. Results: Overall, patients aged 65.6 ±8 yrs, 58% had diabetes, 50% had history of myocardial infarction and 91% were under statin and aspirin therapy. Baseline demographics, risk factors and laboratory data were similar between infusion groups. There was no statistical difference regarding the levels of hsCRP, IL-1β, IL-6, IL-8 and TNF-α from baseline to follow-up between groups, but there was a trend for decrease in IL-6 levels in the LDE-PTX group (-16%), not observed in the placebo group. Regarding the CCTA high-risk plaques, a tendency for reduction of the napking-ring signal after infusion was observed in the LDE-PTX group (figure 1) compared to placebo (p=0.098). No clinical or laboratorial toxicities were observed. Conclusions: This study shows that LDE-PTX was safe in CIHD patients and showed signs of benefits in reducing inflammatory biomarkers and modification of high-risk plaque characteristics.

Altered cytokine profiles in relapsed paucibacillary leprosy: a case report

BackgroundIndividuals with relapses of leprosy should be monitored carefully, however, with respect to paucibacillary (PB) leprosy, it is sometimes difficult to make a definitive diagnosis of relapse, because the bacillary index is often negative. To evaluate the usefulness of cytokine profiling in a patient with relapsed PB leprosy who tested negative for anti-phenolic glycolipid-I antibodies, we analyzed the Mycobacterium leprae protein-induced cytokine expression in peripheral blood mononuclear cells of the patient.Case presentationAn 89-year-old-male relapsed PB patient, first treated for leprosy over 50 years prior, was examined. In April 2012, he noticed three skin lesions consisting of annular erythema in the thighs. Slit skin smear tests were negative, and skin biopsies revealed a pathology of indeterminate-to-borderline tuberculoid leprosy. He received 600 mg of rifampicin once per month and 75 mg of dapsone daily for 12 months. The annular erythemas disappeared after starting treatment. Before treatment, and 6 and 12 months after starting treatment, the Th1/Th2 cytokine profiles in the supernatant of mononuclear cells from the patient before and after stimulation with Mycobacterium leprae soluble protein (MLS) were examined using a Cytometric Bead Array (CBA) Human Th1/Th2 Cytokine Kit II. The CBA Enhanced Sensitivity Flex Set system was applied to detect small amounts of cytokines in the serum just before treatment and one year before relapse. In the culture supernatant, just before treatment, increases in IFN-γ level and the IFN-γ/IL-10 ratio and a decreased IL-6 level were observed without stimulation. Upon stimulation with MLS, just before treatment, both the IFN-γ and TNF levels increased markedly, and twelve months after starting treatment, the IFN-γ and TNF levels decreased greatly. In the serum, just before treatment, increases in IFN-γ and TNF levels and the IFN-γ/IL-10 ratio were evident compared with those measured one year before relapse.ConclusionsCytokine profiling using culture supernatants and serum samples may be useful for the diagnosis of relapsed PB leprosy.

Sodium nitroprusside protects HFD induced gut dysfunction via activating AMPK\u03b1/SIRT1 signaling

BackgroundActivation of Adenosine 5′-monophosphate-activated protein kinase/Sirtuin1 (AMPK/SIRT1) exerts an effect in alleviating obesity and gut damage. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, has been reported to activate AMPK. This study was to investigate the effect of SNP on HFD induced gut dysfunction and the mechanism.MethodsSNP was applied on lipopolysaccharide (LPS) stimulated Caco-2 cell monolayers which mimicked intestinal epithelial barrier dysfunction and HFD-fed mice which were complicated by gut dysfunction. Then AMPKα/SIRT1 pathway and gut barrier indicators were investigated.ResultsSNP rescued the loss of tight junction proteins ZO-1 and occludin, the inhibition of AMPKα/SIRT1 in LPS stimulated Caco-2 cell monolayers, and the effects were not shown when AMPKa1 was knocked-down by siRNA. SNP also alleviated HFD induced obesity and gut dysfunction in mice, as indicated by the decreasing of intestinal permeability, the increasing expression of ZO-1 and occludin, the decreasing levels of pro-inflammatory cytokine IL-6, and the repairing of gut microbiota dysbiosis. These effects were complicated by the increased colonic NO content and the activated AMPKα/SIRT1 signaling.ConclusionsThe results may imply that SNP, as a NO donor, alleviates HFD induced gut dysfunction probably by activating the AMPKα/SIRT1 signaling pathway.

Prec-O2-04 - Functional remodeling of macrophages with anti-PD-L1 and lenalidomide in cutaneous T cell lymphoma

<h3>Background:</h3> M2-like tumor-associated macrophages (TAMs) are the most abundant phenotype that promote the growth of cutaneous T cell lymphoma (CTCL) by inducing immunosuppression. Although PD1/PD-L1blockade has demonstrated efficacy in CTCL, little is known about the effects on tumor-associated macrophages. Here, we report that anti–PD-L1 treatment favorably impacts the phenotype and function of tumor macrophages by polarizing the macrophage compartment toward a more pro-inflammatory phenotype. Understanding the mechanisms of macrophage reprogramming will identify novel therapeutic targets to reverse impaired immunity. <h3>Methods and results:</h3> We used multiplex immunofluorescence staining of lesional skin samples of CTCL patients demonstrating co-localization of PD1 on CD163+ M2 macrophages. Moreover, RNA-seq analysis performed on tissue sections from same CTCL specimens revealed an up-regulation of the TLR, NF-κB and JAK/STAT signaling pathways. To further confirm PD1 expression on M2 TAMs in CTCL, we cultured CD14+ cells from healthy donor-derived peripheral blood in conditioned media (CM) from MyLa cells. We observed macrophage differentiation towards an PD1+ M2 phenotype, with significant CD163, CD206 and PD1 upregulation but not CD80 expression. The TRIF-stimulated NF-κB and JAK/STAT signaling pathways, downstream of both TLR3 and TLR4 were activated in PD1+ M2-like TAMs. Furthermore, our RT-PCR results show significantly elevated IL-10 levels, but decreased IL-1β, CXCL-10 and CXCL-11 compared to control. To determine whether PD1+ M2-like TAMs could be reprogrammed, anti-PD-L1 (durvalumab) and lenalidomide were used for treatment of MyLa-conditioned media induced human peripheral blood monocyte-derived PD1+ M2-like TAMs. The results show that anti-PD-L1 and lenalidomide synergistically increased IL-1β, CXCL-10, and CXCL-11 expression, but significantly decreased IL-10 level compared with the untreated control in vitro through ablation of TLR3, TLR4 and the downstream signaling pathways, which was linked with functional changes in phagocytic activity and cell migration.

IL-1β and IL-10: diagnostic and prognostic potential of cytokines in the assessment of progression of non-alcoholic fatty liver disease in patients with hypertension

Non-alcoholic fatty liver disease (NAFLD) affects about a quarter of the world's population and it is closely linked to hypertension (HT). Pro-inflammatory and anti-inflammatory cytokines play a key role in the pathology progression, and the search for non-invasive biomarkers for the diagnosis of NAFLD remains an important issue.&#x0D; The aim of the study was to determine the diagnostic and prognostic value of IL-1β and IL-10 in assessing the progression of liver parenchyma changes in patients with NAFLD and HT comorbidity.&#x0D; Materials and methods. A study of 115 patients with non-alcoholic steatohepatitis (NASH) was performed. The main group consisted of 63 patients with NASH and HT, 52 patients with isolated NAFLD represented the comparison group. Clinical and laboratory parameters were evaluated, IL-10 and IL-1β levels were measured by ELISA method, ultrasound steatometry and elastography were performed in all patients.&#x0D; Results. The attenuation coefficient and median liver stiffness in NAFLD and HT group significantly exceeded the results in the isolated NAFLD group and in the control group. The IL-1β level in NAFLD and HT group was 17.55 pg/ml, and in isolated NAFLD group the indicator averaged 15.72 pg/ml, which exceeded the control values (8.26 pg/ml). IL-10 level was 12.69 pg/ml and 14.34 pg/ml in patients with comorbid and isolated NAFLD, respectively, while control results averaged 16.19 pg/ml. It were found strong relationship between IL-1β, IL-10 and CRP levels in patients with NAFLD and HT (r=0.61, p=0.024, and r=-0.69, p=0.036, respectively). Inverse correlations were also found between the cytokines IL-1β and IL-10 in NAFLD patients with and without HT (r=-0.61, p&lt;0.001, and r=-0.57, p&lt;0.001, respectively). Changes in the cytokine status of patients with NAFLD at different stages of steatosis and liver fibrosis had been identified.&#x0D; Conclusions. The presence of concomitant HT in patients with NAFLD is associated with greater severity of liver parenchyma changes. NAFLD manifestation is accompanied by increase of IL-1β and decrease of IL-10 levels, and deepening of these deviations were found in patients with comorbidity of NAFLD and HT.&#x0D; Interleukins IL-1β and IL-10 can be defined as biomarkers of NAFLD progression both in its isolated course and in its comorbidity with HT. The possibility of using biomarkers as an independent non-invasive test of diagnosing NAFLD requires further study.

Paternal Resistance Exercise Modulates Skeletal Muscle Remodeling Pathways in Fathers and Male Offspring Submitted to a High-Fat Diet.

Although some studies have shown that a high-fat diet (HFD) adversely affects muscle extracellular matrix remodeling, the mechanisms involved in muscle trophism, inflammation, and adipogenesis have not been fully investigated. Thus, we investigated the effects of 8 weeks of paternal resistance training (RT) on gene and protein expression/activity of critical factors involved in muscle inflammation and remodeling of fathers and offspring (offspring exposed to standard chow or HFD). Animals were randomly distributed to constitute sedentary fathers (SF; n = 7; did not perform RT) or trained fathers (TF n = 7; performed RT), with offspring from mating with sedentary females. After birth, 28 male pups were divided into four groups (n = 7 per group): offspring from sedentary father submitted either to control diet (SFO-C) or high-fat diet (SFO-HF) and offspring from trained father submitted to control diet (TFO-C) or high-fat diet (TFO-HF). Our results show that an HFD downregulated collagen mRNA levels and upregulated inflammatory and atrophy pathways and adipogenic transcription factor mRNA levels in offspring gastrocnemius muscle. In contrast, paternal RT increased MMP-2 activity and decreased IL-6 levels in offspring exposed to a control diet. Paternal RT upregulated P70s6k and Ppara mRNA levels and downregulated Atrogin1 mRNA levels, while decreasing NFκ-B, IL-1β, and IL-8 protein levels in offspring exposed to an HFD. Paternal physical training influences key skeletal muscle remodeling pathways and inflammatory profiles relevant for muscle homeostasis maintenance in offspring submitted to different diets.

Pengaruh Propolis Terhadap Il-6 Pada Diabetes Melitus Tipe 2: A Literature Review

Type-2 diabetes is a metabolic disease characterized by an increase in blood sugar levels due to decreased insulin secretion by pancreatic beta cells, or inappropriate insulin action. The pathophysiology of type-2 diabetes is related to inflammatory mechanisms caused by an increase in proinflammatory cytokines such as IL-6. Propolis has an anti-inflammatory role that can influence type 2 diabetes. To determine the effect of propolis as an anti-inflammatory to the IL-6 cytokines in type 2 Diabetes Mellitus A Literature review by searching electronic databases on Pubmed, ProQuest, and Google Scholar with the keywords "propolis or bee propolis and IL-6 levels or interleukin-6 levels and diabetes type-2 or type-2 diabetes" published in 2010-2020. Based on the search results, 9 journals were found. These articles consist of 5 experimental articles and 4 RCT articles. Five databases reported a decrease in IL-6 levels and three journals stated that there was an increase in IL-6 levels in the type-2 diabetes group after being given propolis. One journal reported no significant difference. Variations in propolis administration and time in IL-6 measurements affected the tendency to decrease IL-6 levels in type 2 diabetes patients. The active components in propolis were influenced by differences in plant resources, collection season, bee species, and solvents used in the extraction. IL-6 levels in the type-2 diabetes group tended to decrease after propolis administration compared to the type-2 diabetes group without propolis administration. IL-6 levels in the type-2 diabetes group increased after propolis administration because IL-6 helps improve chronic inflammation associated with type-2 diabetes.

MiR-122–5p regulates hepatocytes damage caused by BaP and DBP co-exposure through SOCS1/STAT3 signaling in vitro

BaP and DBP are ubiquitously and contemporaneously present in the environment. However, Current studies largely concentrate on the effects of a single pollutant (BaP or DBP). The liver is vital for biogenic activities. The effects of BaP and DBP co-exposure on liver remain unclear. Thus, we treated human normal liver cell (L02 cell) with BaP or/and DBP. We found that compared to individual exposure, co-exposure to BaP and DBP induced further increased levels of AST and ALT. BaP and DBP co-exposure caused further increased levels of IL-2, IL-6, and TNF-α, decreased IL-10 level, and a higher percentage of apoptotic cells and S-phase arrest cells. BaP and DBP co-exposure worsen the decrease of miR-122–5p level and chaos of SOCS1/STAT3 signaling. Dual-luciferase reporter gene assays showed that SOCS1 was a validated target of miR-122–5p. miR-122–5p overexpression alleviated the increased SOCS1 expression, decreased phospho-STAT3 expression, decreased IL-10 level, increased TNF-α levels, increased percentage of apoptosis and S-phase arrest, and cytotoxicity induced by BaP and DBP co-exposure in hepatocytes. These results suggested that miR-122–5p negatively regulated the synergistic effects on apoptosis and disorder of inflammatory factor secretion involved in hepatocyte injury caused by BaP and DBP co-exposure through targeting SOCS1/STAT3 signaling.

Activation of κ-opioid receptor inhibits inflammatory response induced by sodium palmitate in human umbilical vein endothelial cells

ObjectivesThe current study aims to investigate the effect of κ-opioid receptor (κ-OR) activation on sodium palmitate (SP)-induced human umbilical vein endothelial cells (HUVECs) inflammatory response and elucidate the underlying mechanisms. MethodsA hyperlipidemic cell model was established and treated with κ-OR agonist (U50,488H), and antagonist (norbinaltorphimine, nor-BNI), or inhibitors targeting PI3K, Akt or eNOS (LY294002, MK2206-2HCl or L-NAME, respectively). Furthermore, the expression levels of NLRP3, caspase-1, p-Akt, Akt, p-eNOS, and total eNOS were evaluated. Additionally, the production of reactive oxygen species, and levels of inflammatory factors, such as TNF-α, IL-1β, IL-6, IL-1 and adhesion molecules, such as ICAM-1, VCAM-1, P-selectin, and E-selectin were determined. The adherence rates of the neutrophils and monocytes were assessed as well. ResultsThe SP-induced hyperlipidemic cell model demonstrated increased expression of NLRP3 and caspase-1 proteins (P < 0.05) and elevated ROS levels (P < 0.01), and decreased phosphorylated-Akt and phosphorylated-eNOS expression (P < 0.05). In addition, SP significantly increased TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, P-selectin, and E-selectin levels (P < 0.01), decreased IL-10 levels (P < 0.01), and increased the adhesion rates of monocytes and neutrophils (P < 0.01). The SP-induced inflammatory response in HUVECs was ameliorated by κ-OR agonist, U50,488H. However, the protective effect of U50,488H was abolished by κ-OR antagonist, nor-BNI, and inhibitors of PI3K, Akt and eNOS. ConclusionOur findings suggest that κ-OR activation inhibits SP-induced inflammation by activating the PI3K/Akt/eNOS signaling pathway.

Continuous Blood purification on Influenza-Associated Neurological Disease in children: a retrospective cohort study

BackgroundDue to lack of proven therapies, we evaluated the effect of CBP on Influenza-Associated Neurological Disease in children.MethodsA single-center, retrospective, cohort study was conducted in Luoyang, Henan province, China from January 2018 to January 2020. Children (<18 years) with influenza-associated neurological disease were enrolled in the study. Children with indications for CBP and parental consent received CBP (Continuous Blood purification), while others received maximal intensive care treatment because of the absence of parental consent. The outcomes of the CBP and non-CBP groups were compared. Categorical variables were presented as percentage and compared by Chi-square test. Continuous variables were expressed as median (interquartile ranges) and compared with non-parametric independent sample test. Statistical analyses were carried out by SPSS (version 26.0) and p < 0.05 (2 tailed) was considered to be statistically significant.Results30 children with influenza-associated neurological disease were recruited to the study. 18 received CBP and the other 12 received maximal intensive care. There were no differences between CBP and non-CBP children in age, sex, body weight, type of influenza virus, neurological complications, Glasgow score, PIM-2 score and PCIS at admission (p > 0.05). The inflammatory factors (CRP, PCT and IL-6) of 30 cases were tested at admission and after 3 days of admission. In the CBP group, there was a significant decrease in IL-6 levels at 3 days of admission (p = 0.003) and a decrease in CRP and PCT levels, but no significant difference (p > 0.05). In the non-CBP group, there were no significant difference on levels of CRP, PCT and IL-6 at admission and 3-day of admission (p > 0.05). The 28-day mortality was significantly lower in the CBP group compared with the non-CBP group (11.11% vs. 50%, p = 0.034).ConclusionsCBP definitely reduces IL-6 levels significantly. We did find that the survival rate of patients in the CBP group was improved. But we don’t know if there is a relationship between the reduction of IL-6 levels and the survival rate. Trial registration: http://www.chictr.org.cn/index.aspx(ChiCTR2000031754).

Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo.

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1 day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.

Comparison of Outcomes After Breast Cancer Surgery Between Inhalational and Propofol-Based Intravenous Anaesthesia: A Systematic Review and Meta-Analysis.

BackgroundGeneral anaesthesia is the commonly provided for breast cancer surgery, but the effects of inhalational anaesthesia and propofol-based intravenous anaesthesia on short- and long-term outcomes after breast cancer surgery are not clear. In this study, we conduct a meta-analysis of randomized controlled trials (RCTs) to explore the superior anaesthetic for breast cancer surgery patients.MethodsWe searched the Embase, Medline, Cochrane Library, Web of Science, CNKI, and Wanfang databases (up to January, 2021) for RCTs in which inhalational anaesthesia and propofol-based intravenous anaesthesia were compared and short- and long-term outcomes were assessed in breast cancer surgical patients. The meta-analysis was performed by Stata 12.0.ResultsTwenty RCTs with a total of 2201 patients were included. Compared with inhalational anaesthesia, propofol-based intravenous anaesthesia was associated with more postoperative rescue analgesia (I2=0%, RR: 1.18, 95% CI: 1.07–1.30, P=0.001) but a lower incidence of postoperative nausea and vomiting (PONV) (I2=25.5%, RR: 0.71, 95% CI: 0.62–0.81, P<0.001) and postoperative rescue antiemetics (I2=0%, RR: 0.69, 95% CI: 0.58–0.82, P<0.001). Propofol-based intravenous anaesthesia preserved nature killer cell cytotoxicity (I2=86.2%, SMD: 0.76, 95% CI: 0.13–1.39, P=0.018), decreased IL-6 level (I2=98.0%, SMD: −3.09, 95% CI: −5.70– −0.48, P=0.021) and neutrophil-to-lymphocyte ratio (I2=0%, SMD: −0.28, 95% CI: −0.53– −0.03, P=0.030), and increased 2-year recurrence-free survival rate (I2=0%, RR: 1.10, 95% CI: 1.00–1.20, P=0.043) but did not affect recurrence or the overall survival rate (P>0.05).ConclusionPropofol-based intravenous anaesthesia increases postoperative rescue analgesia but reduces PONV compared with inhalational anaesthesia in breast cancer surgery. The benefit of propofol over inhalational anaesthetics in the preservation of anti-cancer immunity is obvious, but it is difficult to conclude that propofol can exert long-term benefits due to the small sample size.

Effects of stress associated with academic examination on the kynurenine pathway profile in healthy students.

The effects of stress on the neuroendocrine, central nervous and immune systems are extremely complex. The kynurenine pathway (KP) of the tryptophan metabolism is recognised as a cross-link between the neuroendocrine- and immune systems. However, the effects of acute stress from everyday life on KP activation have not yet been studied. This study aims to investigate changes in the levels of the KP neuroactive metabolites and cytokines in response to stress triggered by academic examinations. Ninety-two healthy first year medical students benevolently participated in the study. Parameters were measured pre- examination, which is considered to be a high-stress period, and post-examination, as a low-stress period. Stress induced by academic examinations significantly increases the perceived stress scores (p<0.001), serum cortisol levels (p<0.001) and brain-derived neurotrophic factor (BDNF) levels (p<0.01). It decreased IL-10 levels (p<0.05) but had no effect on IL-6 and TNF-alpha levels. Only the KP neuroactive metabolite, 3-hydroxykynurenine (3-HK) significantly increased (p<0.01) in the post-examination period. In addition, the stress scores positively correlated with the levels of cortisol (r2 = 0.297, p<0.01) at post examination. Acute stress triggered by academic examinations increases cortisol and BDNF production and suppresses the anti-inflammatory cytokine, IL-10, but did not increase significantly the levels of other pro-inflammatory cytokines, tryptophan, kynurenine and downstream KP metabolites. The concomitant increased levels of BDNF under the duress of acute examination stress appear to limit the levels pro-inflammatory markers, which may attenuate the action of cortisol and the neuroinflammatory branch of the KP.