Interlukin-6 Levels Research Articles

The protective effects of alamandine on angiotensin II-induced cardiac dysfunction and remodeling in rats

Alamandine (Ala), a relatively recent addition to the renin-angiotensin system (RAS), is a heptapeptide sharing structural similarities with angiotensin-(1-7). This peptide has garnered significant attention due to its distinctive antihypertensive, vasodilatory, and antifibrotic effects. In this study, we sought to determine whether Ala acts as a counter-regulatory agent against angiotensin II-induced cardiac hypertrophy, fibrosis, and inflammation in rats. Male SD rats (n=6 in each group) received a two-week subcutaneous infusion of vehicle (saline), angiotensin II (ANG II, 150 ng/kg/min), or a combination of ANG II and Ala (50 ng/kg/min) via mini osmotic pumps. Left ventricular (LV) function was evaluated through echocardiography. Histological analysis of cardiac hypertrophy and fibrosis was conducted using Hematoxylin Eosin and Trichome-Mason staining, respectively. Compared to the vehicle group, treatment with Ala significantly (*p<0.05) attenuated ANG II-induced cardiac mass (659.27 ± 54.26* vs. 824.48 ± 40.38 mg) with reduced LV thickness and end-diastolic volume. Ala treatment also improved cardiac function, as indicated by reduced global longitudinal strain and myocardial performance index. Histological images revealed that Ala treatment markedly reduced cardiomyocyte area (383.63* ± 7.20 vs 490.59 ± 13.13 μm²) and fibrosis area (5.22* ± 0.93 vs. 9.64 ± 0.36%) in rats treated with ANG II, along with reduced mRNA expression of pro-hypertrophic markers such as brain natriuretic peptide (4.29 ± 0.50* vs 7.53 ± 0.68, fold change) and β-myosin heavy chain (6.11 ± 0.61* vs 10.29 ± 1.02), as well as pro-fibrosis markers collagen 1 (5.72 ± 0.59* vs 10.56 ± 1.69), fibronectin (2.18 ± 0.34* vs 4.69 ± 0.70), and α-smooth muscle actin (2.14 ± 0.42* vs 3.85 ± 0.06), when compared to the rats treated with ANG II alone. Flow cytometry analysis also showed that Ala treatment significantly reduced ANG II-induced immune responses in the heart by reducing immune cell populations including CD4, CD8 T cells, B cells and NK cells, and increasing presence of anti-inflammatory M2 monocytes. Additionally, the mRNA levels of interlukin-6, CD 68, and chemokine monocyte chemoattractant protein-1 were significantly decreased in Ala-treated rats. Furthermore, treatment with Ala reversed ANG II-induced alterations in the mRNA expression of angiotensin-converting enzyme (ACE, 2.05 ± 0.16* vs. 3.08 ± 0.25), angiotensin type 1 receptor (1.45 ± 0.22* vs. 2.56 ± 0.31), and ACE 2 (1.08 ± 0.10** vs. 0.38 ± 0.06) in the LV of the heart. Taken together, these findings demonstrate that alamandine exerts a protective effect against ANG II-induced cardiac dysfunction, hypertrophy, fibrosis, and inflammation, potentially acting as a protective component of the RAS to counteract the adverse effects of ANG II. Alamandine might be a potential therapeutic agent in the treatment of cardiovascular disorders. Supported by NIH grants R01 HL139521 & 155091. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Changes of plasma Rap1A levels in patients with in-stent restenosis after percutaneous coronary intervention and the underlying mechanisms.

Percutaneous coronary intervention (PCI) is one of the most important treatments for coronary artery disease (CAD). However, in-stent restenosis (ISR) after PCI is a serious complication without effective measures for prevention and treatment. This study aims to investigate the Ras-related protein 1A (Rap1A) level in ISR patients and in the tumor necrosis factor-α (TNF-α)-induced inflammatory injury model of human umbilical vein endothelial cells (HUVECs), to explore the role of Rap1A in regulating TNF-α-induced inflammation in HUVECs and to provide a new potential target for ISR prevention and treatment. A total of 60 CAD patients, who underwent PCI between December 2020 and July 2022 from the Department of Cardiovascular Medicine of Xiangya Hospital, Central South University, and re-examined coronary angiography (CAG) 1 year after the operation, were included. After admission, 27 patients were diagnosed with ISR and 33 patients were diagnosed with non-in-stent restenosis (non-ISR) according to the CAG. Clinical data were collected, and the plasma Rap1A level was determined by enzyme linked immunosorbent assay (ELISA). In cell experiments, an inflammatory injury model was established with TNF-α treatment (10 ng/mL, 24 h) in HUVECs. The mRNA and protein expression levels of Rap1A, interlukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) were measured by real-time reverse transcription PCR and Western blotting. Small interfering RNA (siRNA) was used to explore the role of Rap1A in regulating TNF-α-induced inflammation in HUVECs. Compared with the non-ISR patients, a higher proportion of ISR patients had a history of smoking (P=0.005) and diabetes (P=0.028), and higher levels of glycosylated hemoglobin (HbA1c) (P=0.012), low-density lipoprotein cholesterol (LDL-c) (P=0.014), and hypersensitive C-reactive protein (hs-CRP) (P=0.027). The remaining projects did not show significant differences (all P>0.05). The plasma level of Rap1A in the ISR group was significantly higher than that in the non-ISR group [942.14 (873.28 to 1 133.81) μg/mL vs 886.93 (812.61 to 930.98) μg/mL; P=0.004]. Diabetes, LDL-c, and Rap1A were risk factors for ISR by univariate logistic regression analysis (all P<0.05). The mRNA and protein expression levels of inflammatory factors IL-6 and VCAM-1 were increased in HUVECs after 10 ng/mL TNF-α treatment for 24 h compared with the control group (all P<0.05), while the mRNA and protein levels of Rap1A were increased (both P<0.05). After inhibition of Rap1A in HUVECs, the mRNA and protein expression levels of IL-6 and VCAM-1 were significantly decreased (all P<0.05). The plasma Rap1A level was significantly elevated in patients with ISR, suggesting that Rap1A may be a potential biomarker for predicting ISR. In the TNF-α- induced HUVECs inflammatory injury model, the expression level of Rap1A was increased. The level of TNF-α-induced endothelial cell inflammation was decreased after inhibition of Rap1A expression, suggesting that Rap1A may be a potential target for the treatment of endothelial cell inflammation in ISR.

Banana peel ameliorated hepato-renal damage and exerted anti-inflammatory and anti-apoptotic effects in metal mixture mediated hepatic nephropathy by activation of Nrf2/ Hmox-1 and inhibition of Nfkb pathway.

This study evaluated the protective role of banana peel extract (BP) on heavy metal mixture (HMM) mediated hepatorenal toxicity using a rat model. Twenty-five female Wistar albino rats were weight-matched and divided into five groups of five female rats each. Group 1(control) received deionized water only. Group 2 received HMM only (20mgkg-1 of Pb, 0.40mgkg-1 of Hg, 0.56mgkg-1 of Mn and 35mgkg-1 of Al). Groups 3, 4 and 5 were co-administered with the same metal mixture with BP at 200, 400 and 800mgkg-1, respectively. Treatments were through oral gavage for 60 days; animals were sacrificed pentobarbital anesthesia and liver and kidney harvested for test. Thereafter, metal levels, malondialdehyde (MDA) and nitric oxide (NO), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPx), interlukin-6 (IL-6) and tumor necrosis alpha (Tnf-α), caspase-3 (Cas-3), Nuclear factor kappa B (Nfkb), Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (Hmox-1) were assayed. HMM group presented higher levels of metal, IL-6 and Tnf-α, MDA, NO, Nfkb and Hmox-1 in HMM group which were significantly reduced by BP. BP was protective against metal mixture induced histopathological distortions. HMM exposure significantly distorted hepatorenal functions and BP treatment reduced metal bioavailability and abrogated most of these alterations.

Study of the level of leptin and resistin and some biochemical tests for people using ketogenic diet in Kirkuk city

Recently, the keto diet has been relied upon to lose weight, but there are some advantages and disadvantages that could be diagnosed through the current study. The study included 50 individual (male and female) and 25 Control, collected Blood samples for determination of leptin and resistin and Lipid profile. The results showed that the serum level of leptin and resistin were significantly lower in Diet group (2.137 g/l, 4.34 g/l) respectively as compared to healthy control group (leptin; 3.52 g/l, resistin; 4.739g/l) respectively. Lipids profile levels was significantly higher in Ketogenic Diet group, were the results of each (cholestrol -TC, low density lipoprotein-LDL-c, triglycerides -TG) (298 g/dl, 169.9 g/dl, 292.3 g/dl) respectively as compared to healthy control group (159.4 g/dl, 85.4 g/dl, 191 g/dl), while the result of High density lipoprotein (HDL-c) showed lower significantly in Diet group (31.9 g/dl) compared with control group (52.4 g/dl). In conclusion, the results of this study showed following the ketogenic diet increases the level of cholesterol and triglycerides (TG) and causes a reduction in albumin, globulin and total protein levels. The results have also showed an increase in adipokin level and a decrease in leptin level. Whereas, no-significant changes were noticed in both resisten and interlukin-6 levels.

Effects of bifid triple viable on chronic low-grade inflammation in obese mice induced by high fat diet

To explore the effects and possible mechanism of bifid triple viable(BTV) on chronic low-grade inflammation and insulin resistance in obese mice induced by high fat diet(DIO). A total of 18 male C57 BL/6 J mice aged 6 weeks were randomly divided into two groups according to their body weight after adaptive feeding for 2 weeks. Six mice in one group were fed with normal rodent diet as control group. Twelve mice in the other group were fed with high fat diet(60% kcal% fat)(HF). After 8 weeks, it was confirmed that body weight and fasting blood glucose of the mice fed with high fat diet were significantly higher than those of the control group(P&lt;0.001), and then they were randomly divided into HF group and HF+BTV group according to the body weight and fasting blood glucose. Six mice in the HF group continued to be fed with high fat diet. Six mice in the HF+BTV group were fed with high fat diet and administered bifid triple viable suspension by gavage(24 mg/kg body weight), once a day. Mice in the control group and HF group were given equal volume of water as control treatment. After 4 weeks of treatment, blood was collected from tail vein, and the fasting blood glucose was measured by automatic glucose meter. Then the animals were killed and collected blood, distal ileum, liver and epididymal white adipose tissue. The tight junctions between the epithelial cells of ileum mucosa were observed by transmission electron microscopy. Serum endotoxin(also called lipopolysaccharide, LPS) levels were determined by limulus amebocyte lysate assay. Immunohistochemical staining was used to observe the macrophage marker F4/80 in liver and epididymal white adipose tissue. Serum fasting insulin levels, tumor necrosis factor-α(TNF-α), interlukin-6(IL-6) and monocyte chemotactic protein-1(MCP-1) in liver and/or epididymal white adipose tissue were detected by ELISA. The index of homeostasis model assessment of insulin resistance(HOMA-IR) was calculated by formula. Compared with the mice fed with normal rodents diet, the tight junctions between the epithelial cells of ileum mucosa were loose, the levels of serum endotoxin, live TNF-α and IL-6, epididymal white adipose tissue TNF-α, IL-6, MCP-1 were significantly elevated(P&lt;0.05), the number of macrophages increased in liver and epididymal white adipose tissue, fasting glucose, fasting insulin levels and HOMA-IR were significantly up-regulated(P&lt;0.01) in the HF group. In comparison with the HF group, the structures of tight junctions between the epithelial cells of ileum mucosa were normalized, the levels of serum endotoxin, liver TNF-α, IL-6 and epididymal white adipose tissue TNF-α, IL-6, MCP-1 were obviously decreased(P&lt;0.05), the number of macrophages reduced in liver and epididymal white adipocytes, fasting insulin levels and HOMA-IR were significantly down-regulated(P&lt;0.05), but had no effect on fasting blood glucose levels in HF+BTV group. Bifid triple viable may protect intestinal mucosa barrier, alleviate metabolic endotoxemia, thus improve chronic low-grade inflammation in liver and adipose tissue, and partially restore insulin sensitivity in DIO mice by regulating gut microbiota.

Inflammatory Status of Excavated Pulp Tissue and Internal Root Resorption in Pulpotomized Primary Molars.

Internal root resorption after pulpotomy is a pathological phenomenon and can lead to early root resorption and subsequent loss of the tooth. To assess the relationship between initial inflammatory coronal pulp status in decayed primary molars treated by pulpotomy and internal root resorption after one-year follow-up. In this clinical in vivo and in vitro experiment, vital pulpotomies were performed on 50 primary molars from 50 patients aged 5 to 10 years. Coronal pulp was carefully removed followed by hemostasis and placement of a reinforced zinc oxide eugenol over the vital radicular pulp. Enzyme-linked immunosorbent assay (ELISA) assay was done on coronal pulp samples and the level of tumor necrosis factor-alpha (TNF- α) and interlukin-6 (IL-6) was measured. After a 12-month follow-up, periapical radiographs were taken from pulpotomized teeth. Kolmogorov-Smirnov, Chi-square, Kruskal-Wallis, and Mann-Whitney tests were implemented. 11 treated teeth (22%) showed an internal root resorption as diagnosed on X-rays. No significant association was found between TNF- α, IL-6 levels, and pathological root resorption respectively (p= 0.953) and (p= 0.944). A significant association between age and pathological root resorption was observed (p= 0.031). No significant association between remaining dentin thickness and pathological root resorption was established (p= 0.346). There was no association between pro-inflammatory cytokines levels/ TNF-α, IL-6 and internal root resorption following pulpotomy in pediatric patients.

Role of inflammatory and nutritional markers in predicting complications after pancreaticoduodenectomy

BackgroundPancreaticoduodenectomy is associated with considerable morbidity and mortality rates. Early recognition of patients likely to develop severe postoperative complications will allow the timely commencement of a tailored approach. This study aimed to predict postoperative complications using inflammatory and nutritional markers measured early in the postoperative period. MethodsPatients who underwent pancreaticoduodenectomy between June 2019 and November 2020 were included in the study. Postoperative pancreatic fistula, delayed gastric emptying, and postoperative pancreatic hemorrhage were graded according to the International Study Group of Pancreatic Fistula and the International Study Group of Pancreatic Surgery. We also documented other complications such as wound infection, intra-abdominal collection, and nonsurgical complications. Nutritional and inflammatory markers were analyzed on postoperative days 1 and 3. Patients were followed up for 30 days or until discharge, depending on which was longer. ResultsOf the 58 enrolled patients, 51 were included in the study. The incidence of postoperative pancreatic fistula was 51% (clinically relevant postoperative pancreatic fistula 27.4%), delayed gastric emptying was 80.4% (clinically relevant delayed gastric emptying 43%), postoperative pancreatic hemorrhage was 3.9%, intra-abdominal collection was 23.5%, and wound infection was 29.4%. The median drain fluid interlukin-6 levels on postoperative day 1 and postoperative day 3 were significantly higher in patients developing clinically relevant postoperative pancreatic fistula than in those who did not develop clinically relevant postoperative pancreatic fistula on postoperative day 1 (211 [125, 425] fg/dL vs 99 [15, 170] fg/dL, [P = .045]) and on postoperative day 3 (110 [22, 28] fg/dL vs 10 [1.8, 45] fg/dL [P = .002]). Patients who tested negative for urine trypsinogen-2 on postoperative day 3 had a significantly lower probability of developing clinically relevant postoperative pancreatic fistula than those who tested positive (1 vs 24 [P < .001]). A model comprising both drain fluid interlukin-6 and urine trypsinogen-2 on postoperative day 3 definitively ruled out the occurrence of clinically relevant postoperative pancreatic fistula. ConclusionDrain fluid interlukin-6 and urine trypsinogen-2 on postoperative day 3 ruled out the occurrence of clinically relevant postoperative pancreatic fistula.

Measuring the Systemic Inflammatory Response to On- and Off-Pump Coronary Artery Bypass Graft (CABG) Surgeries Using the Tryptophan/Kynurenine Pathway

Background: Cardiac surgeries induce many inflammatory responses with remarkable clinical implications. Tryptophan (Trp) is a precursor for serotonin, melatonin and kynurenine (Kyn). Plasma kynurenic acid (Kyna) and Kyn concentrations are thought to be related to the severity of inflammation. Plasma Trp/Kyn ratio is used to measure inflammatory cytokine activity. Methods: We performed the current longitudinal study in a tertiary care center and included 62 patients divided into two groups; group A (on-pump CABG patients) and group B (off-pump CABG patients). Plasma Trp and Kyn were measured using the high-performance liquid chromatography (HPLC) technique. Serum interlukin-6 (IL-6) and white blood cells (WBCs) were measured using ELISA and routine blood count, respectively. Results: The present study revealed that the intraoperative levels of plasma Kyn, IL-6 and WBCs were significantly increased while the plasma Trp/Kyn ratio was significantly decreased in both the groups; however, the changes were more significant in the on-pump CABG group. Moreover, the levels in both the groups returned to preoperative levels 72 h postoperative. Our study has shown that WBCs is positively correlated with IL-6, but has negative correlation with Trp/Kyn ratio. Conclusions: Kyn and Trp/Kyn ratio might be utilized as markers of the severity of inflammation in major surgery. In addition, off-pump CABG might be more preferable than on-pump CABG regarding stress and release of inflammatory markers.

Effect of Snakehead Fish and Sea Cucumber Extract Administration on Mast Cell Infiltration, Interlukin-6 (IL-6), and Albumin Levels in Burns and Surgical Wounds

Introduction: Burn injury impairs almost every organ system, which causes significant morbidity and mortality. Meanwhile, the phases included in burn healing are inflammation, cell recruitment, matrix deposition, epithelialization, and tissue remodeling phase. Previous studies showed that snakehead fish and sea cucumber extract have these effects and are beneficial in burn and post-surgery wounds. Objective: This study aims to analyze the effect of snakehead fish and sea cucumber extract supplementation towards mast cell infiltration, IL-6, and albumin level in burn and post-surgery wounds. Materials and Methods: A double-blind randomized control trial was carried out at Dr. Moewardi Hospital Surakarta in November 2017 on 30 subjects, which were divided into 2 groups. Mast cell infiltration was observed on burn and post-surgery wounds colored with Toluidine Blue, while IL-6 and albumin were measured -blood, where both groups had comparable basic characteristics. Results and Discussion: There was a statistically insignificant (p=0.835) higher increase in albumin level in the treatment group, while an insignificant (p=0.056) greater decrease also occur in the IL-6 level. The decrease in cell mast infiltration after treatment was also higher and not statistically significant (p=0.526). Previous studies showed that amino acids from snakehead fish play an important role in wound healing. Meanwhile, high EPA content in sea cucumber is due to its ability as an Echinodermata to regenerate tissue. It was also discovered that the results available about sea cucumber and sea snake extract on wound healing are different based on the skin condition after the use of the extracts. Conclusion: Snakehead fish and sea cucumber extract supplementation can increase albumin level, decrease IL-6 level and mast cell infiltration in burn or post-surgery wounds.

ROLE OF INTERLEUKIN-6 AND PROCALCITONIN AS INFLAMMATORY BIOMARKERS IN EVALUATING COVID-19 DISEASE SEVERITY ON HRCT CHESTAN EXPERIENCE AT CMH QUETTA

Objective: To explore the relation of Interleukin-6 and Procalcitonin with COVID-19 severity on high resolution computerized tomogram (HRCT) chest.&#x0D; Study Design: Randomized Control Trial (NCT04945811).&#x0D; Place and Duration of study: Pathology Department, Combined Military Hospital Quetta, from April 2020 to May 2021.&#x0D; Methodology: Serum Interleukin-6 and Procalcitonin of 100 consenting COVID-19 positive patients from April 2020 to May 2021 were assessed at Pathology department Combined Military Hospital Quetta and their levels were correlated with severity of lung involvement on HRCT Chest&#x0D; Results: Serum Interlukin-6 levels were significantly raised in 97 patients with mean levels of 20.43 ± 19.66 (pg/ml). Serum procalcitonin levels were also significantly raised in 95 patients with mean levels of 0.43 ± 0.24 (ng/ml).&#x0D; Conclusion: Interlukin-6 and procalcitonin are important biomarkers for diagnosis and predicting severity of COVID-19 pneumonia.

The role of tocilizumab therapy in critically ill patients with severe acute respiratory syndrome coronavirus 2.

Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor antagonist, has been approved for use in rheumatoid arthritis and cytokine storm syndrome (CSS) associated with chimeric antigen receptor Tcells treatment. Although TCZ is currently utilized in the treatment of critically ill coronavirus 2019 (COVID-19) patients, data on survival impact is minimal. To assess the mortality rate of patients presenting with COVID-19 who received TCZ for suspected CSS. This retrospective cohort study was conducted at Henry Ford Health System between March 10, 2020 and May 18, 2020. Data collection began in May 2020 and was completed in June 2020. Patients included in the study required hospital admission and had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction on nasopharyngeal swab. Eligibility criteria to receive TCZ, per hospital protocol, included any of the following: persistent fever, defined as 38.0°C for at least 6hours; a diagnosis of the acute respiratory distress syndrome (ARDS); serum ferritin≥1,000 (ng/mL) or doubling within 24hours; D-Dimer≥5 (mg/L); serum lactate dehydrogenase≥500 (IU/L); or interlukin-6 level≥5 times the upper limit of normal. Dosing was initially determined by weight, then changed to a fixed 400mg per hospital protocol. A comparator cohort was created from patients with COVID-19 and ARDS who did not receive TCZ. Patient survival was analyzed using the Kaplan-Meier method and compared by log rank test. A multivariable cox regression was applied to evaluate the association between TCZ and mortality. One hundred and thirty patients were evaluated in the study, 54 (41.5%) of whom received TCZ. Patients who received TCZ were younger (mean age, 63.8 vs. 69.4years; p=0.0083) and had higher body mass indices (mean, 33.9 vs. 30.4; p=0.005). Of the comorbid conditionsevaluated, heart disease was more common in the comparator group than the TCZ group (27 patients [35.5%] vs. 10 patients [18.5%]; p=0.034). A Kaplan-Meier survival curve demonstrated no difference in survival between TCZ and comparator patients (log rank p=0.495). In the multivariable Cox regression model for mortality at 30days, treatment with TCZ was not associated with decreased mortality (hazard ratio, 1.1; 95% confidence interval, 0.53-2.3; p=0.77). Lower mean C-reactive protein (CRP) levels were demonstrated within 48hours of disposition in the TCZ group (mean TCZ, 4.9 vs. mean comparator, 13.0; p=<0.0001). In this cohort study, no difference in survival was observed in critically ill patients treated with TCZ.

Effects of domestic solid fuel combustion emissions on the biomarkers of homemakers in rural areas of the Fenwei Plain, China

BackgroundThe health effects of heavy solid fuel use in winter in rural China are of concern. The effects of air pollution resulting from domestic solid fuel combustion in rural households on rural homemakers’ biomarkers were revealed in this study. MethodsIn total, 75 female homemakers from rural areas of Guanzhong Basin, the Fenwei Plain, People’s Republic of China, were randomly selected and divided into three groups (biomass users, coal users, and nonusers of solid fuel user [control group]). The differences in biological indicators, including 8-hydrox-2′-deoxyguanosine (8-OHdG), interlukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in urine samples as well as blood pressure (BP, including systolic BP [SBP] and diastolic BP [DBP]) and heart rate (HR) among the groups in winter and summer were investigated using statistical analysis. ResultsIL-6, 8-OHdG, HR, SBP, and DBP were significantly higher in winter than in summer (P < 0.05) owing to the poor air quality resulted from the excessive use of solid fuels in winter. Significant seasonal differences in 8-OHdG were observed for both coal and biomass users. After the influence of confounders was removed, only IL-6 levels in the urine of solid fuel users were significantly higher than that of the control group. ConclusionsIL-6 is a sensitive biomarker representing inflammatory responses to particulate matter emitted through household solid fuel combustion. Locally, excessive use of solid fuels in winter posed serious PM2.5 pollution in this area and adverse effects on inflammatory biomarkers in these rural homemakers and induced DNA damage related to oxidative stress.

MiR-608 overexpression in idiopathic pulmonary fibrosis (IPF)

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the usual interstitial pneumonia pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered ‘human specific’. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology.ObjectiveTo test miR-608 expression and its targets in IPF patient samples.MethodsRNA was extracted from Formalin fixed paraffin embedded tissue sections (N = 18). miRNA-608 and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its’ rs17228616 allele has a single-nucleotide polymorphism causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease and this region was sequenced for assessment of rs17228616 allele polymorphism.ResultsmiR-608 is significantly overexpressed in IPF samples in comparison with controls (p < 0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p < 0.001 and p < 0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p = 0.01, OR = 2.1, CI 95% [1.19–3.9]).ConclusionmiR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.

Coconut Oil Nanoemulsion Loaded with a Statin Hypolipidemic Drug for Management of Burns: Formulation and In Vivo Evaluation.

Burn wound healing is a complex process that involves the repair of injured tissues and the control of infection to diminish the scar formation, pain, and discomfort associated with such injuries. The aim of this research was to formulate and optimize a self-nanoemulsion drug delivery system based on the use of coconut oil and loaded with simvastatin. Coconut oil possesses antiinflammatory and antibacterial activity, and simvastatin has interesting properties for promoting the wound-healing process because it increases the production of the vascular endothelial growth factor at the site of injury. The Box–Behnken design was employed for the optimization of the coconut oil–simvastatin self-nanoemulsion drug delivery system. The prepared formulations were characterized according to globular size and their activity in the healing of burn wounds by assessing the mean wound diameter and level of interlukin-6 in experimental animals. Additionally, the antimicrobial activity of the prepared formulations was assessed. The nanoemulsion was considered adequately formed when it had droplets of between 65 and 195 nm. The statistical design proved the important synergistic effect of coconut oil and simvastatin for burn wound management in their synergistic potentiation of wound closure and their anti-inflammatory and antimicrobial effects. The optimum formulation achieved up to a 5.3-fold decrease in the mean burn wound diameter, a 4.25-fold decrease in interleukin-6 levels, and a 6-fold increase in the inhibition zone against Staphylococcus aureus when compared with different control formulations. Therefore, the designed nanoemulsions containing a combination of coconut oil and simvastatin could be considered promising platforms for the treatment of chronic and burn wounds.

Can soy isoflavones plus soy protein change serum levels of interlukin-6? A systematic review and meta-analysis of randomized controlled trials.

In the present review, we aimed to summarize the effect of soy isoflavones plus soy protein on circulating interlukin-6 (IL-6) in adult participants. Databases including ISI Web of Science, PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched up to 23 March 2020. The mean change from baseline of IL-6 concentrations and its SD for intervention and comparison groups were used to calculate the effect size. If the heterogeneity test was statistically significant, DerSimonian and Laird random effects model was used. Cochran's Q test and I-squared statistic were also used to compute the statistical heterogeneity of the intervention's effects. Eighteen studies were known to be eligible for systematic review and 14 studies were selected for meta-analysis. Our meta-analysis results indicated a non-significant effect in serum IL-6 concentrations compared to the comparison group (WMD = 0.03 pg/ml, 95% CI: -0.06, 0.12; p = .459). In subgroup analysis, based on soy isoflavones dosage, it was observed that this combination could reduce IL-6 levels in studies that used isoflavones with dose >84 mg/day (WMD = -0.12 pg/ml 95% CI: -0.24, -0.004; p = .042, I2 = 82.7%) and in articles with a good quality (WMD = -0.15 pg/ml 95% CI: -0.24, -0.05; p = .003, I2 = 62.3%). Performing well-designed intervention studies using a high dose of soy isoflavones is recommended to confirm the beneficial effects of soy ingredients on IL-6.

Relationship of cutaneous manifestations with inflammatory markers in diabetic nephropathic patients on haemodialysis

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Diabetic nephropathy is a serious life threatening complication of type-2 diabetes mellitus. Apart from severe kidney dysfunction these patients are prone to various cutaneous complications including psoriasis and eczema due to accumulated nitrogenous waste products. Inflammation is the basic cause of cutaneous complications and many inflammatory markers have been shown elevated in chronic kidney dysfunction. Hence a study has been planned to assess the levels of inflammatory markers such has C-reactive protein (CRP) and interlukin-6 (IL-6) as well as to correlate these markers with creatinine levels along with existing cutaneus complications.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; The study included 50 diabetic nephropathic patients undergoing regular heamodialysis. A heparanised blood sample was collected and plasma was employed for estimation of glucose, creatinine, CRP and IL-6. A detailed dermatological examination was done to record the cutaneous complications like pruritis, xerosis, hyper pigmentation and half &amp;amp; half nails.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; The results show a significant raise in CRP and IL-6 levels in proportion to the severity of kidney dysfunction as reflected by creatinine levels. Also a positive relationship was observed between the inflammatory markers and multiplicity of cutaneous complications.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; It can be concluded from the present study that evaluation of inflammatory markers, CRP and IL-6 along with creatinine is beneficial in controlling cutanious complications in DN patients undergoing regular heamodialysis.&lt;/p&gt;

Status of Interlukin-6 and lipid profile in depression disorder

Introduction: Present study was conducted to evaluate the role of interlukin-6 and lipid profile in patients of depression. Materials and Methods: A case-control study consisted of 100 patients and 50 controls, who were attending psychiatric O.P.D in Geetanjali medical college & hospital, Udaipur Rajasthan. Inclusion criteria-depressive subjects those attending psychiatric O.P.D of Geetanjali hospital (20-60yrs). Exclusion criteria- patients undergoing treatment of any other hypertension, diabetes, cardiovascular disorders documented by physical & clinical examination. Level of IL-6 and lipid profile was measured in serum. Analysis was done using SPSS version 16.0 at significant level of 95% confidence level and p-value ?0.005. Results: The mean total cholesterol level in depression patients was 136.08±24.08, mean HDL-c was 41.97±16.50, mean LDL-c was 109.33±21.06, mean triglycerides level was 134.28±16.02 and mean interlukin-6 level was 4.19±1.33. The mean total cholesterol level in controls was 182.3±35.76, mean HDL-c was 51.3±13.08, mean LDL-c was 121.9±25.69, mean triglycerides level was 154.7±24.45 and mean interlukin-6 level was 2.02±0.43. We found that there is a significant negative correlation between interlukin-6, total cholesterol (-0.730) and triglycerides (-0.896). There is significant positive correlation between interlukin-6 and LDL-c (0.977). Conclusion: Depression is undoubtedly a multidimensional disorder. IL-6 exerts a multilayered effect on determinants of behavior, and understanding the role of IL-6 in the pathophysiology of depression may facilitate the elucidation of its effect on alterations in lipid metabolism. Keywords: Cholesterol, Depression, HDL, Interlukin-6, LDL, Triglycerides.

High-glucose administration induces glucose intolerance in mice: a critical role of toll-like receptor 4.

Glucose converted from a diet has been considered a high-risk factor of type 2 diabetes mellitus (T2DM). However, it is not clear how it increases the risk of T2DM. Here, we investigated the effect of high-glucose administration on glucose tolerence in wild-type and toll-like receptor 4 (TLR4) knockout mice. Mice were intragastrically administered with high-glucose. The level of fasting blood glucose, insulin and intraperitoneal glucose tolerance were measured, and insulinogenic index and HOMA-IR were calculated at 1 week. To understand mechanism of glucose action, we also assessed blood glucose, glucagon-like peptide-1 and inflammatory cytokines levels at different time windows following high-glucose load. Our results show that 20 g/kg glucose load leads to glucose tolerance impairment and insulin resistance in wild-type mice. Following 20 g/kg glucose load, the levels of plasma interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) increased significantly in wild-type mice, but not in TLR4 knockout mice. Moreover, 20 g/kg glucose load also impaired glucose-induced GLP-1 secretion in wild-type and TLR4 knockout mice. Our results indicate that high-glucose load leads to glucose intolerance with insulin resistance through impairment of GLP-1 secretion, increase of blood glucose levels via activating TLR4 and increasing levels of IL-6 and TNF-α in mice.

D-pinitol attenuates cisplatin-induced nephrotoxicity in rats: Impact on pro-inflammatory cytokines

Cisplatin has been widely used as a first-line agent against various forms of solid cancers. However, nephrotoxicity is the major limiting factor for its clinical use. Several clinical and pre-clinical studies have suggested different strategies for the reduction of cisplatin-induced nephrotoxicity. The present study was conducted to investigate the efficacy of D-Pinitol, against cisplatin-induced nephrotoxicity in Swiss albino mice. A single intraperitoneal injection of cisplatin (20 mg/kg) was used to induce nephrotoxicity in mice. Administration of cisplatin in mice is linked with elevated oxidative stress, imbalanced biochemical parameters, apoptosis and stimulation of mitogen-activated protein kinase (MAPK) pathway. D-Pinitol is a member of the flavonoid family and a chief constituent of Sutherlandia fruitesecnce. It was administered with saline water (10, 20, 40 mg/kg, p.o.) for seven consecutive days after a single dose of cisplatin. At the end of experiment, animals were sacrificed and biochemical parameters in serum and urine were recorded. Kidneys were isolated for the estimation of tumor necrosis factor-alpha, interleukin-1β, interlukin-6 levels and histopathological evaluations. It was noted that D-Pinitol significantly ameliorated biochemical levels of serum and urinary creatinine and blood urea nitrogen. Tissue homogenate levels of TNF-α, IL-6, IL-1β and the renal expression of tissue nitrites were also significantly decreased in D-Pinitol treated mice. These results were supplemented by histopathological findings. This study highlights the potential role of D-Pinitol against cisplatin-induced toxicity, exhibited through favorable alterations in biochemical and histological changes as well as reduction in oxidative stress and cytokine levels.

Level of inflammatory factors in chronic hemodialysis patients with and without cardiovascular disease.

Background:Considering the existence of controversies about the predictive value of inflammatory markers for cardiovascular disease (CVD), we aimed to compare the level of high-sensitivity C-reactive protein (hs-CRP) and interlukin-6 (IL-6) level in chronic hemodialysis (HD) patients with and without CVD.Materials and Methods:In this historical cohort study, HD patients with and without CVD disease were enrolled. The presence of CVD risk factors, level of inflammatory factors including IL-6 and hs-CRP as well as lipid levels, fasting blood sugar, and other biochemical factors were compared in two studied groups.Results:During the study, eighty HD patients with (n = 40) and without (n = 40) CVD were enrolled. Diabetes was more prevalent among HD patients with CVD than those without CVD (P < 0.05). The level of IL-6 and hs-CRP were not different in two studied groups (P > 0.05). Univariate analysis of variance test indicated that there was not any significant relationship between hs-CRP and CVD (P > 0.05).Conclusion:The findings indicated that the level of inflammatory factors including hs-CRP and IL-6 are not significantly different in HD patients with and without CVD. However, for obtaining more definite conclusion in this field and evaluation their predicting role in this field, it is recommended to study other novel inflammatory markers as well as the additive effect of the inflammatory factors with traditional ones in larger sample size and longer follow-up.