Current understandings and perspectives on non-cancer health effects of benzene: A global concern

Objective

Benzene, as a volatile organic compound, is known as one of the main air pollutants in the environment. The aim of this review is to summarize all available evidences on non-cancerous health effects of benzene providing an overview of possible association of exposure to benzene with human chronic diseases, specially, in those regions of the world where benzene concentration is being poorly monitored.

Methodology

A bibliographic search of scientific databases including PubMed, Google Scholar, and Scirus was conducted with key words of “benzene toxic health effects”, “environmental volatile organic compounds”, “diabetes mellitus and environmental pollutants”, “breast cancer and environmental pollution”, “prevalence of lung cancer”, and “diabetes prevalence”. More than 300 peer reviewed papers were examined. Experimental and epidemiologic studies reporting health effects of benzene and volatile organic compounds were included in the study.

Results

Epidemiologic and experimental studies suggest that benzene exposure can lead to numerous non-cancerous health effects associated with functional aberration of vital systems in the body like reproductive, immune, nervous, endocrine, cardiovascular, and respiratory.

Conclusion

Chronic diseases have become a health burden of global dimension with special emphasis in regions with poor monitoring over contents of benzene in petrochemicals. Benzene is a well known carcinogen of blood and its components, but the concern of benzene exposure is more than carcinogenicity of blood components and should be evaluated in both epidemiologic and experimental studies. Aspect of interactions and mechanism of toxicity in relation to human general health problems especially endocrine disturbances with particular reference to diabetes, breast and lung cancers should be followed up.     

Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line

In diabetic nephropathy, glomerular mesangial cells exhibit aberrant anabolic activity that includes excessive production of extracellular matrix (ECM) proteins, leading to crowding of filtration surface areas and possible renal failure. In the present study, a murine mesangial cell line (MES-13 cells) was studied to determine the roles of the renin-angiotensin system (RAS) and the insulin-like growth factor (IGF) axis in the anabolic response to elevated glucose levels. Culture of MES-13 cells in medium containing supra-physiological glucose concentrations (>5.5 mmol/l) resulted in increased production of ECM proteins including laminin, fibronectin, and heparan sulfate proteoglycan with concurrent increases in IGF-binding protein (IGFBP)-2 production. These responses were blocked by the angiotensin receptor antagonists saralasin and losartan, while exogenous angiotensin II (Ang II) treatment directly stimulated increases in ECM and IGFBP-2. In all experiments, IGFBP-2 levels were correlated with anabolic activity implicating IGFBP-2 as a possible mediator in cellular responses to high glucose and Ang II. Such mediation appears to involve IGFBP-2 modulation of IGF-I signaling, since all responses to high glucose or Ang II were blocked by immuno-neutralization of IGF-I. These data suggest alterations in the IGF axis as key mechanisms underlying nephropathic responses of mesangial cells to Ang II and high glucose.     

Severe hyperglycemia: a determinant factor for hypofiltration in alloxan diabetic rats

Abstract. The relationships among glomerular filtration rate, renal plasma flow and extracellular fluid volume were investigated in control and severely hyperglycemic (442±33 mg/dl) untreated, alloxan diabetc rats. Most of diabetic animals showed significant lower values of inulin clearance (diabetics, 0.55±0.07 ml/min·100 g; controls, 0.97±0.04) and p-aminohippurate clearance (diabetics, 2.11±0.39 ml/min·100 g; controls, 3.93±0.25). Diabetic rats exhibited reduced efficiency in tubular Na⁺ reabsorption, increased urinary Na⁺ excretion (diabetics, 3.12±0.27 mEq/day; controls, 1.25±0.14) and diminished values of plasma renin activity (diabetics, 3.34±0.44 ng/ml·h; controls, 8.64±0.79). Significant negative correlations were found between glycemia and renal hemodynamic variables. Acute overload with glucose further decreased these variables in both groups: inulin clearance in diabetics vs. controls, 0.26±0.04 vs. 0.44±0.05 ml/min·100 g; p-aminohippuric acid clearance in diabetics vs. controls, 1.09±0.20 vs. 1.55±0.21 ml/min·100 g. We conclude that chronically hyperglycemic alloxan diabetic rats showed diminished glomerular filtration rates (inulin clearance), renal plasma flow (p-aminohippurate clearance) and extracellular fluid volume associated with urinary Na⁺ losses and alterations in the renin-angiotensin system. Decreased reninangiotensin system activity might reduce aldosterone secretion, which in turn could result in (succesively) urinary sodium loss, extracellular fluid volume contraction and reductions in glomerular filtration and renal plasma flow.     

Cardiac cell therapy: Current status,challenges and perspectives

Cardiac cell therapy, illustrating cell type, mode of delivery and mechanism of action. CSC: cardiac stem cells; IV: intravenous; MI: myocardial infarction; MNC: mononuclear cells; MOA: mechanism of action; MSC: mesenchymal stromal cells; PSC: pluripotent stem cells.

     

胰腺星状细胞凋亡研究进展

胰腺纤维化是各类慢性胰腺炎的共同特征,胰腺星状细胞(PSC)在胰腺纤维化进程中起重要作用。诱导胰腺星状细胞发生凋亡不仅可抑制纤维化的进展,而且还能为慢性胰腺炎的治疗提供可能的理想途径。但目前胰腺星状细胞凋亡的具体机制尚未完全明了,国内尚无相关报道。     

Extracellular directed ag NPs formation and investigation of their antimicrobial and cytotoxic properties

The use of microbial cell culture a valuable tool for the biosynthesis of nanoparticles is considered a green technology as it is eco-friendly, inexpensive and simple. Here, the synthesis of nanosilver particle (AgNP) from the yeast, Saccharomyces cerevisiae, gram (+), Bacillus subtilis and gram (?), Escherichia coli was shown. In this field we are the first to study their the antimicrobial effects of the microorganisms mentioned above against pathogens and anticancer activity on MCF-7 cell line. Silver nanoparticles in the size range of 126–323?nm were synthesized extracellularly by the microorganisms, which have different cell structures. Optical absorption, scanning electron microscopy, and zetasizer analysis confirmed the silver nanoparticles formation. Antimicrobial activity of AgNPs was evaluated the minimum inhibition concentration and disc diffusion methods. AgNPs inhibited nearly 90% the growth of Gram-positive Listeria monocytogenes, Streptococcus pneumoniae and Gram-negative Haemophilus influenzae, Klebsiella pneumoniae, Neisseria meningitidis bacterial pathogens. Anticancer potentials of AgNPs were investigated by MTT method. The synthesized AgNPs exhibited excellent high toxicity on MCF-7 cells and had a dose-dependent effect on cell viability. Especially AgNP 2 eliminated 67% of the MCF-7 cells at the concentration of 3.125?μg/mL. We found that extracellular synthesis of nanoparticles from microbial culture may be ‘green’ alternative to physical and chemical methods from the point of view of synthesis in large amounts and easy process.     

Load independent impairment of reverse remodeling after valve replacement in hypertensive aortic stenosis patients

Background

We evaluated the impact of hypertension on the left ventricular mass regression in aortic stenosis after aortic valve replacement.

Methods

We prospectively studied 135 patients with severe aortic stenosis at baseline and 1 year after surgery. In 32 patients we analyzed myocardial gene expression of collagen types I and III, connective tissue growth factor, transforming growth factor-β1, metalloproteinase-2 and its tissue inhibitor and compared its levels vs controls.

Results

Seventy-six patients (56.3%) had a history of hypertension. Hypertensive patients were older, had higher Euroscore-II and NYHA class, with no differences in stenosis severity. At 1 year follow-up there was a median decrease of mass index of 14.2% (P25–75: − 4.3%–30.4%; p < 0.001). Mass regression was significantly higher in patients without hypertension, with a median decrease of 25.9% (P25–75: 12.0%–38.7%) vs 5.4% (P25–75: − 12.5%–20.1%; p = 0.001), despite similar increase in effective orifice area and no differences in valvuloarterial impedance. After 1 year, higher baseline left ventricular mass index (p = 0.005) and the absence of hypertension (p = 0.002) or diabetes (p = 0.041) were the only independent predictors of mass regression higher than the median. Comparing with controls, aortic stenosis patients had an increased expression of collagen types I and III, but only hypertensive patients had higher relative expression of collagen type I vs III. In hypertensive patients TIMP2 expression was up-regulated and correlated with higher baseline left ventricular mass index (r = 0.61; p = 0.020).

Conclusions

In aortic stenosis, hypertension impairs mass regression one year after valve replacement, independently of total afterload. Differences in the expression of extracellular matrix remodeling genes might contribute to this finding.     

Stochastic non-enzymatic modification of long-lived macromolecules - A missing hallmark of aging

Damage accumulation in long-living macromolecules (especially extracellular matrix (ECM) proteins, nuclear pore complex (NPC) proteins, and histones) is a missing hallmark of aging. Stochastic non-enzymatic modifications of ECM trigger cellular senescence as well as many other hallmarks of aging affect organ barriers integrity and drive tissue fibrosis. The importance of it for aging makes it a key target for interventions. The most promising of them can be AGE inhibitors (chelators, O-acetyl group or transglycating activity compounds, amadorins and amadoriases), glucosepane breakers, stimulators of elastogenesis, and RAGE antagonists.     

督脉电针对脊髓损伤后MAPK/ERK/1/2信号通路的影响

目的 观察督脉电针对脊髓损伤（SCI）小鼠MAPK/ERK1/2信号通路相关蛋白表达的影响。 方法 采用随机数字表法将64只C57BL/6小鼠分为假手术组、脊髓损伤组、督脉针刺组和督脉电针组。将脊髓损伤组、督脉针刺组及督脉电针组小鼠制成SCI动物模型。假手术组及脊髓损伤组小鼠制模后均未给予特殊处理,督脉针刺组小鼠于制模后次日给予单纯针刺治疗（取穴大椎、命门）,督脉电针组小鼠于制模后次日给予电针治疗,取穴方法同督脉针刺组,电刺激设置疏密波（2/100 Hz）,电刺激强度0.2 mA。于制模后3 d、7 d、14 d及28 d时分别采用免疫荧光、蛋白印迹法测定各组小鼠受损脊髓p-ERK1/2、p-Akt及髓鞘碱性蛋白(MBP)表达情况。 结果 与脊髓损伤组同期比较,督脉电针组在制模后3 d、14 d及28 d时,督脉针刺组在制模后28 d时其受损脊髓p-ERK1/2蛋白表达均显著增强(P<0.05);与督脉针刺组比较,督脉电针组在制模后3 d、14 d时其受损脊髓p-ERK1/2蛋白表达均明显增强(P<0.05)。督脉电针组在制模后14 d、28 d时,督脉针刺组在制模后28 d 时其受损脊髓p-Akt蛋白表达均较脊髓损伤组显著增强(P<0.05),督脉针刺组在制模后3 d时其受损脊髓p-Akt蛋白表达较脊髓损伤组明显减弱(P<0.05)。督脉电针组在制模后3 d、7 d、14 d时,督脉针刺组在制模后3 d、7 d时其受损脊髓MBP蛋白表达均较脊髓损伤组明显增强(P<0.05)。 结论 督脉电针可促进SCI小鼠p-ERK1/2、p-Akt及MBP蛋白表达。