Protein-1 Levels Research Articles

Associations of childhood adiposity with adult intima-media thickness and inflammation: a 20-year longitudinal population-based cohort.

The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking. The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male], and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ± 2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores. A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity. In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity.

Increased visinin-like protein-1, YKL-40, lipocalin-2, and IL-23 levels in patients with migraine

ABSTRACT Background Migraine is a type of primary headache caused by changes in the trigeminal system and has been reported to be associated with neurovascular inflammation of cerebral and extracerebral vessels. Objective It is known that inflammation is an important process in the pathogenesis of migraine. It has been shown that the molecules of visinin-like protein 1 (Vilip-1), YKL-40, lipocalin-2 and interleukin (IL)-23 play a role in the inflammatory process. Our aim is to investigate the role of this molecule in the metabolic pathway of migraine disease. Methods Fifty migraine patients with and without aura in the interictal period were included in the study. Vilip-1, YKL-40, lipocalin-2, and IL-23 levels were measured by ELISA method. Results Serum vilip-1, YKL-40, lipocalin-2, and IL-23 levels were found to be significantly higher in migraine patients compared to the control group. We found that this molecule increased significantly in migraine subgroups compared to the control group (p < 0.001). A positive significant correlation was found between vilip-1 level and YKL-40 and lipocalin-2 levels in migraine patients. In addition, a positive correlation was observed between visual analogue scale score, number of days with pain and vilip-1 level (p < 0.01). The results of our study showed that activation of inflammatory mediators may play a role in the pathogenesis of migraine disease. In addition, our study is valuable in that inflammatory molecules are high in the interictal period and these biomarkers have never been analyzed in migraine patients. However, we still believe that larger studies are needed to explain the role of vilip-1, YKL-40, lipocalin-2, and IL-23 in the molecular mechanism of migraine disease.

Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells

Androgen receptor splice variant (AR-V) expression has been associated with prostate cancer (PCa) progression to castration-resistant PCaduring androgen deprivation therapy, which reduces androgen production and inhibits androgen action in PCa cells. However, the mechanisms whereby aberrant AR-V expression is increased in PCa are still largely unknown. Fibroblasts in tumor stroma influence PCa initiation and aggressiveness, and which may play a crucial role in eliciting genetic changes during malignant transformation in human prostate epithelium. Here, our aim was to determine whether prostate fibroblasts in tumor stroma induce aberrant AR-V7 expression in PCa cells under low androgen concentration. We performed in vitro experiments using androgen-sensitive, AR-positive PCa cell lines (LNCaP and 22Rv1 cells), commercially available prostate stromal cells (PrSC), and primary cultured prostate fibroblasts (pcPrF) from PCa specimens collected from biopsies of patients with advanced PCa. PCa cells were cocultured with each of the three fibroblast lines (PrSC, pcPrF-M37, and pcPrF-M48). The proliferation under low androgen concentration of LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 was significantly increased compared to that of PCa cells cultured alone. Androgen receptor-full length (AR-FL) protein expression was increased in LNCaP and 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. AR-V7 protein expression was increased in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. Under low androgen concentration, AR-V7 protein expression was slightly detected in LNCaP cells cocultured with PrSC or pcPrF-M37. Cytokine array analysis revealed that monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) levels in the conditioned medium of 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48 were increased under low androgen concentration. High IL-8 concentration (30 ng/ml) resulted in significantly increased protein expression of AR-FL, AR-V7, and phospho-NF-κB p65 in 22Rv1 cells. In contrast, IL-8 antibody (1 µg/ml) decreased AR-V7 protein expression in 22Rv1 cells cocultured with PrSC, pcPrF-M37, or pcPrF-M48. pcPrF from PCa specimens increase the expression of aberrant AR-V7 in PCa cells. IL-8 may be a target for preventing the expression of aberrant AR-Vs in PCa.

Ethnic differences in urinary monocyte chemoattractant protein-1 and heparanase-1 levels in individuals with type 2 diabetes: the HELIUS study

IntroductionWe aimed to investigate ethnic differences in two urinary inflammatory markers in participants with type 2 diabetes mellitus (T2DM).Research design and methodsWe included 55 Dutch, 127 South-Asian Surinamese, 92 African...

Estimation of Monocyte Chemoattractant Protein-1 (MCP-1) Levels as an Inflammatory Cytokine in Chronic Generalized Periodontitis Patients

Published on: October 2022Journal of Young Pharmacists, 2022; 14(4):430-434Original Article | doi:10.5530/jyp.2022.14.87 Authors:Anushri Gupta1,*, Sumedha Srivastava1, Veena Kalburgi1, Ashutosh Dubey1, Sai Sri Harsha Nimmala1, Meghaanshu Gupta21Department of Periodontology, People’s College of Dental Sciences and Research Centre, Bhopal, Madhya Pradesh, INDIA.2Dental Surgeon, Private Practitioner, Etah, Uttar Pradesh, INDIA. Abstract:Background: Monocyte chemoattractant protein-1 (MCP-1) performs assignment of inflammatory cells by triggering the chemotaxis of monocytes and also various cellular events related with chemotaxis. Its increased GCF, saliva and serum levels in periodontal disease have been reported in previous studies. The present study is aimed to evaluate the part of MCP-1 in periodontal disease continuation and also to find out the effect of periodontal treatment on MCP-1 concentration in serum and saliva. Materials and Methods: A total of 60 subjects were divided into three groups (n = 30): chronic periodontitis pre-scaling and root planning (group I), chronic periodontitis consisted of 30 subjects from group I, 4-6 weeks after treatment (group II) and healthy control (group III). Clinical parameters evaluated were gingival index (GI), oral hygiene index-simplified (OHI-S), probing pocket depth (PPD), clinical attachment level (CAL), and serum and saliva samples collected from each patient were quantified for MCP-1 using ELISA. Results: The mean MCP-1 concentration in serum and saliva was found to be the highest in group I, i.e. 160.54 pg/ml and 444.62 pg/ml respectively. The mean MCP-1 concentration in group II was 81.79 pg/ml and 262.98 pg/ml and in group III, it was 43.43 pg/ml and 151.91 pg/ ml respectively. Conclusion: MCP-1 level in serum and saliva rise with advancement of disease and decline after phase I therapy. Due to its certain correlation with clinical parameters, it can be examined as an inflammatory biomarker in periodontal disease. Hence, MCP-1 needs to be further reviewed as a therapeutic target.Keywords: Chemokine, Chronic generalized periodontitis, Inflammatory biomarker, Monocyte Chemoattractant Protein -1 (MCP-1), Non-surgical periodontal therapy..

The KLF4-p62 axis prevents vascular endothelial cell injury via the mTOR/S6K pathway and autophagy in diabetic kidney disease.

Diabetic kidney disease (DKD) is a complication of systemic diabetic microangiopathy, which has a high risk of developing into end-stage renal disease and death. This study explored the mechanism underlying autophagy in DKD vascular endothelial cell injury. DKD and vascular endothelial cell injury models were established using Sprague Dawley rats and human umbilical vein endothelial cells (HUVECs). HUVECs overexpressing Kruppel-like factor 4 (KLF4) were constructed by transient transfection of plasmids. Biochemical determination of urinary protein and blood urea nitrogen (BUN), superoxide dismutase (SOD), and creatinine (Scr) levels was performed. Renal pathology was observed by periodic acid-Schiff (PAS) staining. Cell Counting Kit-8 (CCK8), terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), and immunocytochemistry (ICC) were used to analyse the growth and apoptosis of HUVECs. Microtubule-associated protein light chain 3 (LC3) expression was observed by immunofluorescence (IF). The reactive oxygen species (ROS) levels were measured using flow cytometry. Monocyte chemoattractant protein-1 (MCP-1), KLF4, and tumour necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). The expression of KLF4, p62 protein, and LC3 was analysed using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). S6 kinase (S6K), p70 ribosomal S6 kinase (p-S6K), Beclin1, ATG5, LC3, p62, Caspase-3, mammalian target of rapamycine (mTOR), and phsophorylated mTOR (p-mTOR) expressions were detected by western blotting. PAS-positive substances (polysaccharide and glycogen) and S6K protein levels increased, and LC3 protein expression decreased in DKD rats. The levels of urinary protein, BUN, and Scr increased, and KLF4 decreased in DKD rats. High glucose (HG) levels decreased the proliferation and increased the apoptosis rate of HUVECs. The expression of ROS, TNF-α, MCP-1, and p62 increased, while the expression of SOD, KLF4, Beclin1, ATG5, and LC3 decreased in HG-induced HUVECs. KLF4 overexpression significantly increased Beclin1, ATG5, and LC3 protein expression and decreased p62 protein expression compared to the oe-NC group in HG-induced HUVECs. KLF4 overexpression inhibits the expression of Caspase-3, p-mTOR, and p-S6K in HG-induced HUVECs. KLF4-p62 axis improved vascular endothelial cell injury by regulating inflammation and the mTOR/S6K pathway in DKD.

Examination of antimicrobial effect of fluoxetine in experimental sepsis model: An in vivostudy.

Since most infectious diseases can develop into sepsis, it is still a major medical problem. Some in-vivo studies showed promising properties of fluoxetine in the treatment of infections. This study aims the antimicrobial effect of fluoxetine on the inflammatory process used in the treatment of sepsis-modeled rats. Besides, to investigate the efficacy of fluoxetine on modifying the antibiotic effect of imipenem in the inflammatory response.An experimental sepsis model was divided intonegative control, positive control, fluoxetine 5 mg/kg, imipenem 60 mg/kg, and combined (fluoxetine; imipenem). Procalcitonin (PCT),high-sensitivity C-reactive protein (hs-CRP), lactate, myeloperoxidase activity (MPO), the inflammation markers interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels were measured by enzyme-linked immunosorbent assay method. Oxidative stress markers, total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), and native thiol (NT) were measured using photometric methods. Oxidative stress index (OSI) was calculated according to TAS and TOS levels. The statistical analysis was performed by Statistical Package for Social Sciences version 22.0.After treatment with fluoxetine, imipenem, and combined groups, IL-1β, IL-6, TNF-α, MPO activity, MCP-1, hs-CRP, PCT, lactate, and the oxidative stress markers OSI, and disulfide levels were decreased (p < 0.05). The TT, NT, and TAS levels significantly statistically increased (p < 0.05).This research demonstrates that fluoxetine has effects as anti-inflammatory and antioxidant, and the combined treatment with antibioticum imipenem indicates positive synergistic effects in the experimental sepsis model.

Evaluation of the effect of phytosomal curcuminoids on oxidative stress and inflammatory markers in NAFLD: A randomized double-blind placebo-controlled trial

• Non-alcoholic fatty liver disease (NAFLD) is one of the major public health challenges of the 21st century. • Oxidative stress (OS) is widely regarded as one of the most important factors in the pathophysiology of this disease. • The potential of curcumin in reducing inflammation and oxidative stress has been investigated in many studies. • Daily use of phytosomal curcuminoids in patients with NAFLD resulted in a significant increase in CAT activity and a significant reduction in MCP-1. The aim of this study was to evaluate the effects of the phytosomal curcuminoids on oxidative stress and inflammatory biomarkers along with routine biochemical factors in non-alcoholic fatty liver disease (NAFLD). Seventy-two patients were selected and randomly divided into Placebo and Curcumin groups (250 mg of phytosomal curcuminoids daily for two months). Biochemical, inflammatory biomarkers including interleukin (IL) 6, IL-10, TNFα (tumor necrosis factor alpha), MCP-1 (monocyte chemoattractant protein-1) and high-sensitivity C-reactive protein (hsCRP) and oxidative stress measurements including malondialdehyde (MDA), superoxide dismutase (SOD) and Catalase (CAT) were measured between two groups before and after the intervention. Curcumin treatment statistically significant increased the activity of CAT enzyme compared with the Placebo group after intervention ( p value = 0.001). However, no significant changes were observed in MDA and SOD biomarkers. Moreover, there was a statistically significant reduction in monocyte chemoattractant protein-1 (MCP-1) levels as a chemokine in the Curcumin group compared with the Placebo group after treatment ( p value = 0.007). Daily use of 250 mg of phytosomal curcuminoids for two months in patients with NAFLD resulted in a significant increase of CAT activity and a significant reduction of MCP-1.

Circulating Monocyte Chemoattractant Protein-1 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Substudy of SHOCK-COOL Trial

Background: There is evidence that monocyte chemoattractant protein-1 (MCP-1) levels reflect the intensity of the inflammatory response in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) and have a predictive value for clinical outcomes. However, little is known about the effect of mild therapeutic hypothermia (MTH) on the inflammatory response in patients with CS complicating AMI. Therefore, we conducted a biomarker study to investigate the effect of MTH on MCP-1 levels in patients with CS complicating AMI. Methods: In the randomized mild hypothermia in cardiogenic shock (SHOCK-COOL) trial, 40 patients with CS complicating AMI were enrolled and assigned to MTH (33 °C) for 24 h or normothermia at a 1:1 ratio. Blood samples were collected at predefined time points at the day of admission/day 1, day 2 and day 3. Differences in MCP-1 levels between and within the MTH and normothermia groups were assessed. Additionally, the association of MCP-1 levels with the risk of all-cause mortality at 30 days was analyzed. Missing data were accounted for by multiple imputation as sensitivity analyses. Results: There were differences in MCP-1 levels over time between patients in MTH and normothermia groups (P for interaction = 0.013). MCP-1 levels on day 3 were higher than on day 1 in the MTH group (day 1 vs day 3: 21.2 [interquartile range, 0.25–79.9] vs. 125.7 [interquartile range, 87.3–165.4] pg/mL; p = 0.006) and higher than in the normothermia group at day 3 (MTH 125.7 [interquartile range, 87.3–165.4] vs. normothermia 12.3 [interquartile range, 0–63.9] pg/mL; p = 0.011). Irrespective of therapy, patients with higher levels of MCP-1 at hospitalization tended to have a decreased risk of all-cause mortality at 30 days (HR, 2.61; 95% CI 0.997–6.83; p = 0.051). Conclusions: The cooling phase of MTH had no significant effect on MCP-1 levels in patients with CS complicating AMI compared to normothermic control, whereas MCP-1 levels significantly increased after rewarming. Trial registration: NCT01890317.

The radiographic assessment of lung edema score of lung edema severity correlates with inflammatory parameters in patients with coronavirus disease 2019-Potential new admission biomarkers to predict coronavirus disease 2019 worsening.

BackgroundCoronavirus disease 2019 (COVID-19) has placed enormous pressure on intensive care units (ICUs) and on healthcare systems in general. A deeper understanding of the pathophysiology of the most severe forms of COVID-19 would help guide the development of more effective interventions. Herein, we characterized the inflammatory state of patients with COVID-19 of varying degrees of severity to identify admission biomarkers for predicting COVID-19 worsening.DesignAdmission blood samples were obtained from 78 patients with COVID-19. Radiographic assessment of lung edema (RALE) scoring was calculated by imaging. Platelet and leukocyte counts were measured by flow cytometry, and plasma levels of C-reactive protein were assessed by immunoturbidimetry, and interleukin (IL)-8/CXCL8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monocyte chemoattractant protein-1 (MCP-1/CCL2) levels by enzyme-linked immunosorbent assay (ELISA).ResultsThe RALE score correlated with several admission hemogram (platelets, neutrophils, and lymphocytes) and inflammatory (IL-8/CXCL8, MCP-1/CCL2, IL-10, and C-reactive protein) parameters. COVID-19 worsening, based on the need for oxygen (Δoxygen supply) during hospitalization, correlated negatively with admission lymphocyte counts but positively with neutrophil-to-lymphocyte ratio and with plasma levels of the inflammatory parameters correlating with RALE score.ConclusionOur data indicate a correlation between the RALE score and Δoxygen supply and admission inflammatory status. The identification of a panel of biomarkers that reflect COVID severity might be useful to predict disease worsening during hospitalization and to guide clinical management of COVID-19-related complications. Finally, therapies targeting IL-8/CXCL8- or IL-10 activity may offer therapeutic approaches in COVID-19 treatment.

Changes in Tears Monocyte Chemoattractant Protein-1 Level After External Dacryocystorhinostomy in Primary Acquired Nasolacrimal Duct Obstruction.

The authors aimed to define tears monocyte chemoattractant protein-1 (MCP-1) changes after external dacryocystorhinostomy surgery. Tears samples were collected with a Schirmer strip and stored in Eppendorf tubes at -80°C. At the end of the study, the papers were cut into small pieces and incubated with phosphate-buffered saline solution. Monocyte chemoattractant protein-1 levels were determined by using an enzyme-linked immunosorbent assays kit. The MCP-1 levels were 498.66±101.35, 576.40±149.78, 422.53±85.94, and 436.96±81.38ng/L before surgery, in the first week, the first, and third months after surgery, respectively. Its level significantly increased in the first week compared with the preoperative level ( P <0.001). There was a prominent decrease in the postoperative first month ( P <0.001). In the third postoperative month, the mean MCP-1 level was not significantly increased compared with the postoperative first month ( P =0.196). The tears MCP-1 level was significantly decreased after external dacryocystorhinostomy surgery.

Remote ischemic preconditioning causes transient cell cycle arrest and renal protection by a NF-κB-dependent Sema5B pathway.

Acute kidney injury increases morbidity and mortality, and previous studies have shown that remote ischemic preconditioning (RIPC) reduces the risk of acute kidney injury after cardiac surgery. RIPC increases urinary high mobility group box protein-1 (HMGB1) levels in patients, and this correlates with kidney protection. Here, we show that RIPC reduces renal ischemia-reperfusion injury and improves kidney function in mice. Mechanistically, RIPC increases HMGB1 levels in the plasma and urine, and HMGB1 binds to TLR4 on renal tubular epithelial cells, inducing transcriptomic modulation of renal tubular epithelial cells and providing renal protection, whereas TLR4 activation on nonrenal cells was shown to contribute to renal injury. This protection is mediated by activation of induction of AMPKα and NF-κB; this induction contributes to the upregulation of Sema5b, which triggers a transient, protective G1 cell cycle arrest. In cardiac surgery patients at high risk for postoperative acute kidney injury, increased HMGB1 and Sema5b levels after RIPC were associated with renal protection after surgery. The results may help to develop future clinical treatment options for acute kidney injury.

Soluble low density lipoprotein receptor-related protein-1 levels in the differential diagnosis of myopericarditis versus acute coronary syndrome

IntroductionDifferential diagnosis of myopericarditis (MPC) versus acute coronary syndromes (ACS) can be difficult in the emergency room (ER). Low density lipoprotein receptor-related protein-1 (LRP-1) is a transmembrane receptor with diverse biological functions. LRP-1 is increased after viral infections as a defense mechanism. sLRP-1 (soluble form) can be measured in the serum. We study the diagnostic sLRP-1 levels in patients with MPC, ACS and healthy controls. MethodsThe study included consecutive patients who were admitted between the dates of 1.1.2018 and 1.1.2019 with the diagnosis of MPC or ACS. All patients reported to the ER with chest pain (CP) and elevated cardiac troponin levels. Control group (n = 61) was selected from healthy subjects. In addition to routine laboratory work up, serum sLRP-1 concentrations were measured on admission. ResultssLRP-1 levels were significantly higher in MPC, compared to controls (p = 0.005) and ACS (p = 0.001). Median (IQR) sLRP-1 levels in MPC, controls and ACS were 7.39 (22.42), 2.27 (1.74), 2.41 (0.98) μg/ml, respectively (p = 0.004). Among the covariates: sLRP-1, age, gender, HDL-C and LDL-C; only sLRP-1 differentiated a diagnosis of MPC versus ACS (OR = 1684, p = 0,046, CI for OR (1008-2812). The area under the curve (AUC) was measured as 0.79 [CI 0.62–0.95] in ROC analysis, p = 0.001; sLRP-1 had 69% sensitivity and 85% specificity for diagnosis of MPC with a cut-off value of 4.3 μg/ml. ConclusionsLRP-1 is a potential biomarker in the differential diagnosis of MPC versus ACS in ER. Future studies are needed to evaluate and develop the utility of sLRP-1 as a diagnostic and prognostic biomarker in MPC.

Clinical Efficacy of Huangkui Capsule plus Methylprednisolone in the Treatment of Nephropathy and the Effect on Urinary Protein and Serum Inflammatory Factors in Patients.

Objective The study aimed to assess the clinical efficacy of Huangkui capsule plus methylprednisolone in the treatment of nephropathy and the effect on urinary protein and serum inflammatory factors in patients. Methods Between June 2017 and July 2020, 90 patients with nephropathy admitted to our hospital were recruited after assessment of eligibility and assigned via the random number table method (1 : 1) to receive either methylprednisolone tablets (observation group) or methylprednisolone tablets plus Huangkui capsules (experimental group). All eligible patients were also given dipyridamole and valsartan. Outcome measures included clinical efficacy, urine protein, hematuria, serum inflammatory factor levels, and adverse reactions. Results A higher clinical efficacy was observed in the experimental group versus the observation group (P < 0.05). Huangkui capsules resulted in significantly lower levels of urine protein and hematuria in the experimental group versus the observation group after treatment (P < 0.05). The serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and monocyte chemoattractant protein-1 (MCP-1) levels in the experimental group were significantly lower than those in the observation group after treatment (P < 0.05). Huangkui capsules plus methylprednisolone were associated with a lower incidence of adverse events versus methylprednisolone (P < 0.05). Conclusion The clinical efficacy of Huangkui capsule plus methylprednisolone in the treatment of patients with nephropathy is remarkable. It can effectively mitigate the inflammatory responses and enhance renal function, with reliable clinical safety, so it is worthy of clinical application.

Effects of 2-Year Nutritional and Lifestyle Intervention on Oxidative and Inflammatory Statuses in Individuals of 55 Years of Age and over at High Cardiovascular Risk.

Obesity and overweight are disorders with high impact on the morbidity and mortality of chronic diseases, such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). We aim to assess the effects of 2-year nutritional and lifestyle intervention on oxidative and inflammatory status in individuals of 55 years of age and over at high CVD risk. Participants (n = 100 individuals of 55 years of age and over living in the Balearic Islands, Spain) were randomized into control and intervention group. Anthropometric and haematological parameters, blood pressure and physical activity were measured before and after the intervention. Oxidative and inflammatory biomarkers in plasma, urine, peripheral blood mononuclear cells (PBMCs) and neutrophils were determined. A higher reduction in abdominal obesity, blood pressure and triglycerides levels was observed after a 2-year intervention. An improvement of oxidative stress and proinflammatory status was demonstrated with a significant reduction in myeloperoxidase, xanthine oxidase, malondialdehyde and monocyte chemoattractant protein-1 (MCP1) levels, and an increase in polyphenols in plasma was observed. A decrease in reactive oxygen species production in PBMCs and neutrophils levels after zymosan and lipopolysaccharide activation was found in the intervention group with respect to the control group. The intervention with hypocaloric Mediterranean Diet and customized physical activity improves oxidative stress and proinflammatory status and could contribute to decreasing the CVD risk.

Inflammation Induced by Lipopolysaccharide and Palmitic Acid Increases Cholesterol Accumulation via Enhancing Myeloid Differentiation Factor 88 Expression in HepG2 Cells.

Recently, multiple studies have shown that chronic inflammation disturbs cholesterol homeostasis and promotes its accumulation in the liver. The underlying molecular mechanism remains to be revealed. The relationship between the toll-like receptor 4 (TLR4) inflammatory signaling pathway and cholesterol accumulation was investigated in HepG2 cells treated with lipopolysaccharide (LPS) or palmitic acid (PA) for different lengths of time. In addition, the effects of pretreatment with 20μmol/L ST2825 (MyD88 inhibitor) were also studied in LPS- or PA-treated HepG2 cells and myeloid differentiation factor 88 (MyD88)-overexpressing HEK293T cells. The intracellular total and free cholesterol levels were measured using a commercial kit and filipin staining, respectively. The expression levels of sterol regulatory element-binding protein-2 (SREBP-2) and components in the TLR4 signaling pathway were determined using Western blotting. The treatments with LPS for 12 h and with PA for 24 h significantly increased the contents of intracellular total and free cholesterol, as well as the expression levels of SREBP-2 and components in the TLR4 signaling pathway. The inhibition of MyD88 by ST2825 significantly decreased the cholesterol content and the expression levels of SREBP-2 and components of the TLR4/MyD88/NF-κB pathway in HepG2 cells, as well as MyD88-overexpressing HEK293T cells. These results indicated that LPS and PA treatments increase SREBP-2-mediated cholesterol accumulation via the activation of the TLR4/MyD88/NF-κB signaling pathway in HepG2 cells.

Dietary adenosine 5'-monophosphate supplementation increases food intake and remodels energy expenditure in mice.

BackgroundDietary nucleotides [inclusion adenosine 5’-monophosphate (AMP)] supplementation was shown to promote the feed intake of sows and increase the AMP content in their milk in our previous work, but whether AMP shapes the energy expenditure and lipid metabolism in mammals remains unknown. Here, we aimed to explore the effects and the related mechanism of dietary AMP supplementation on food intake, body composition, energy expenditure, and lipid metabolism in male mice.Methods4-week-old C57BL/6 mice (After a 1-wk adaptation) were fed with basal diet and basal diet supplemented with 0.1% AMP, respectively. Animal food intake and body weight were monitored and after 4 weeks all animals were sacrificed to measure the body composition, energy expenditure and lipid metabolism changes.ResultsCompared with the control, the 0.1% AMP fed mice showed higher food intake while lower adipose weight. Intriguingly, dietary AMP supplementation was found to stimulate brown adipose tissue thermogenesis as evidenced by the increase in the uncoupling protein-1 level and the core temperature. Moreover, AMP supplementation was shown to promote white adipose tissue lipolysis as indicated by smaller lipid droplet size in mice. These results demonstrate that dietary AMP supplementation could enhance oxygen consumption and energy expenditure.ConclusionsThis study highlights the physiological importance of AMP supplementation in mediating food intake and energy expenditure and suggests its potential as an adjuvant therapy in preventing energy metabolic disorders (mainly obesity and diabetes).

Enriched Environment-Induced Neuroprotection against Cerebral Ischemia-Reperfusion Injury Might Be Mediated via Enhancing Autophagy Flux and Mitophagy Flux.

Background Enriched environment (EE) can protect the brain against damages caused by an ischemic stroke; however, the underlying mechanism remains elusive. Autophagy and mitochondria quality control are instrumental in the pathogenesis of ischemic stroke. In this study, we investigated whether and how autophagy and mitochondria quality control contribute to the protective effect of EE in the acute phase of cerebral ischemia–reperfusion injury. Methods We exposed transient middle cerebral artery occlusion (tMCAO) mice to EE or standard condition (SC) for 7 days and then studied them for neurological deficits, autophagy and inflammation-related proteins, and mitochondrial morphology and function. Results Compared to tMCAO mice in the SC group, those in the EE group showed fewer neurological deficits, relatively downregulated inflammation, higher LC3 expression, higher mitochondrial Parkin levels, higher mitochondrial fission factor dynamin-related protein-1 (Drp1) levels, lower p62 expression, and lower autophagy inhibitor mTOR expression. Furthermore, we found that the EE group showed a higher number of mitophagosomes and normal mitochondria, fewer mitolysosomes, and relatively increased mitochondrial membrane potential. Conclusion These results suggested that EE enhances autophagy flux by inhibiting mTOR and enhances mitophagy flux via recruiting Drp1 and Parkin to eliminate dysfunctional mitochondria, which in turn inhibits inflammation and alleviates neurological deficits. Limitations. The specific mechanisms through which EE promotes autophagy and mitophagy and the signaling pathways that link them with inflammation need further study.

Serum retinol binding protein-4 and the risk of hypothyroidism in Egyptian diabetic patients with cardiovascular manifestations

Retinol binding protein-4 (RBP4) levels have been associated with patients of type 2 diabetes (T2DM) including insulin resistance (IR), dyslipidemia, and cardiovascular disease (CVD). The present study examined the relationship between serum levels of RBP4 and the risk factors related to hypothyroidism (Hypo) and CVD in diabetic Egyptian patients. A total of 96 subjects were recruited and divided into 8 groups. Subjects were assessed for different biochemical parameters. In addition, serum levels of RBP4 were measured using specific immunoassays. There was a highly statistically significant difference in fasting blood glucose (FBG) and hemoglobin A1C (HbA1c) between the different patient groups and the control group. Thyroid stimulating hormone (TSH) concentration in the (T2DM+Hyp) group was considerably higher than in the other groups. There were statistically significant variations in TSH levels between all groups and controls. The mean RBP4 value in Group5 (T2DM+Hyp+CVD) was significantly higher than in the other groups. In (T2DM+Hypo+CVD) group, the receiver operating characteristic (ROC) curve revealed that RBP4 had a higher area under curve (AUC), making it a powerful discriminator of those diseases.

Serological biomarkers for management of primary sclerosing cholangitis.

Clinical manifestations and progression of primary sclerosing cholangitis (PSC) are heterogeneous, and its pathogenesis is poorly understood. The importance of gut-liver interactions in the pathogenesis has been clinically confirmed and highlighted in different theories. Recent advances regarding biomarkers of biliary-gut crosstalk may help to identify clinically relevant PSC subgroups assisting everyday clinical work-up (e.g., diagnosis, disease stratification, or surveillance) and the exploration of potential therapeutic targets. Alkaline phosphatase produced by the biliary epithelium is consistently associated with prognosis. However, its level shows natural fluctuation limiting its use in individual patients. Inflammatory, cell activation, and tissue remodeling markers have been reported to predict clinical outcome. Elevated immunoglobulin (Ig) G4 level is associated with a shorter transplantation-free survival. IgG type atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCAs) are non-specific markers of various autoimmune liver diseases and may reflect an abnormal B-cell response to gut microbial antigens. IgG type atypical P-ANCA identifies PSC patients with particular clinical and genetic (for human leukocyte antigens) characteristics. The presence of IgA type anti-F-actin antibody (AAA) may predict a progressive disease course, and it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage. IgA type anti-glycoprotein 2 (GP2) antibodies identify patients with a severe disease phenotype and poor survival due to enhanced fibrogenesis or development of cholangiocarcinoma. Elevated soluble vascular adhesion protein-1 (sVAP-1) level is associated with adverse disease outcomes in PSC. High sVAP-1 levels correlate with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in the liver that contributes to gut activated T-cell homing to the hepatobiliary tract. In the present paper, we review the evidence on these possible serological markers that could potentially help address the unmet clinical needs in PSC.