Angiogenic activity of mitochondria; beyond the sole bioenergetic organelle.

Angiogenesis is a complex process that involves the expansion of the pre-existing vascular plexus to enhance oxygen and nutrient delivery and is stimulated by various factors, including hypoxia. Since the process of angiogenesis requires a lot of energy, mitochondria play an important role in regulating and promoting this phenomenon. Besides their roles as an oxidative metabolism base, mitochondria are potential bioenergetics organelles to maintain cellular homeostasis via sensing alteration in oxygen levels. Under hypoxic conditions, mitochondria can regulate angiogenesis through different factors. It has been indicated that unidirectional and bidirectional exchange of mitochondria or their related byproducts between the cells is orchestrated via different intercellular mechanisms such as tunneling nanotubes, extracellular vesicles, and gap junctions to maintain the cell homeostasis. Even though, the transfer of mitochondria is one possible mechanism by which cells can promote and regulate the process of angiogenesis under reperfusion/ischemia injury. Despite the existence of a close relationship between mitochondrial donation and angiogenic response in different cell types, the precise molecular mechanisms associated with this phenomenon remain unclear. Here, we aimed to highlight the possible role of mitochondria concerning angiogenesis, especially the role of mitochondrial transport and the possible relation of this transfer with autophagy, the housekeeping phenomenon of cells, and angiogenesis.

Copper (II) complexes with N, S donor pyrazole-based ligands as anticancer agents.

A group of bidentate nitrogen and sulfur donor pyrazole derivative ligands abbreviated as Na[RNCS(Pz)], Na[RNCS(PzMe2)], Na[RNCS(PzMe3)], Na[RNCS(PzPhMe)], Na[RNCS(PzPh2)], where (R = Et, Ph), and their Cu (II) complexes were synthesized and characterized by spectroscopic and physicochemical methods. The crystal structure of [Cu(PhNCSPzMe3)2] was determined by X-ray crystallography analysis and the results described a distorted square planar coordination geometry for this complex. Also, the cyclic voltammetry investigations indicated that the synthesized copper complex is an electrochemically active species. Moreover, the cytotoxic activity of all of the twenty synthesized compounds was evaluated using MTT assay against the MCF-7 (human breast carcinoma) cell lines, in vitro. Cu (II) complexes indicate significant cytotoxicity against the MCF-7 cell lines as compared with the free ligands. The docking studies showed that the copper complexes have better interactions with EGFR and CDK2 proteins, compared to the free ligands, and most of the studied compounds have a higher value of binding energy relative to the studied controls. The results of QSAR analysis suggest that dipole moment is in direct correlation with the obtained IC50 values, and it strongly impact the anticancer effects generated by the compounds. Our findings suggest that the developed copper complexes can be good candidates for further evaluations as chemotherapeutic agents in the treatment of cancer.

Label-free electrochemical microfluidic biosensors: futuristic point-of-care analytical devices for monitoring diseases.

The integration of microfluidics with electrochemical analysis has resulted in the development of single miniaturized detection systems, which allows the precise control of sample volume with multianalyte detection capability in a cost- and time-effective manner. Microfluidic electrochemical sensing devices (MESDs) can potentially serve as precise sensing and monitoring systems for the detection of molecular markers in various detrimental diseases. MESDs offer several advantages, including (i) automated sample preparation and detection, (ii) low sample and reagent requirement, (iii) detection of multianalyte in a single run, (iv) multiplex analysis in a single integrated device, and (v) portability with simplicity in application and disposability. Label-free MESDs can serve an affordable real-time detection with a simple analysis in a short processing time, providing point-of-care diagnosis/detection possibilities in precision medicine, and environmental analysis. In the current review, we elaborate on label-free microfluidic biosensors, provide comprehensive insights into electrochemical detection techniques, and discuss the principles of label-free microfluidic-based sensing approaches.

Association of Paraoxonse1 (PON1) Genotypes with the Activity of PON1 in Patients with Parkinson's Disease.

OBJECTIVE: Various numbers of factors such as oxidative stress, neurotoxins, and pesticides have been implicated in its pathophysiology of Parkinson's disease (PD). Paraoxonas1 (PON1) metabolizes xenobiotics, including pesticides. Therefore, we surveyed the relationship between PON1 polymorphisms with its activities in the pathogenesis of Parkinson's disease.. METHODS: We investigated polymorphisms of the PON1 (L55M and Q192R) by PCR-RFLP assays; we also measure the levels of PON1, TAC (total antioxidant capacity) and TOS (total oxidant status) with ELISA (Enzyme-linked immunosorbent assay) and spectrophotometric method for their activities. RESULTS: Paraoxonase and arylesterase activity of PON1 as well as their concentrations were lower in patients with PD compared with control group, but from the view of the specific activity, it was not significant between two groups. In the compare of TAC, TOS, and OSI, the TOS and OSI were higher in the patients than controls, while patients had lower levels of TAC compared with controls. Serum PON1 concentrations and activities were higher in LL (comparison with LM and MM) and RR (comparison with QR and QQ) genotypes while we did not observe any significant differences in arylesterase levels among mentioned polymorphisms. CONCLUSION: In the current study, we reported associations between PON1 polymorphisms (55, 192) and enzyme activities in Parkinson's disease as there was a significant reduction in PON1 levels in patients with Parkinson compared with healthy. Taken together, paraoxonase enzyme in subjects with different genotypes could be a potential biomarker for determining the severity and prognosis of Parkinson. However, more studies are needed to clarify its clinical values. Key words: Parkinson's disease; paraoxonase1; Polymorphism.

A methodological approach for purification and characterization of human serum albumin.

As the most predominant protein in plasma, albumin is synthesized in the liver. Given to various applications of albumin as biopharmaceutical agent, the annual demand for it is 500 tons in the world, which is the highest in the biomedical solutions demand ranking. There exist different procedures for production of albumin. The aim of this study was the purification of human serum albumin (HSA) using immunoaffinity chromatography. After immunization of rabbits, passive immunodiffusion and indirect ELISA tests were applied for assessment of polyclonal antibody production against HSA. Purification was performed by ion exchange chromatography (IEC) and protein G affinity chromatography. The produced anti-HSA IgG was attached to the CNBR-activated Sepharose and applied for albumin purification from human serum. Western blotting (WB) analysis and heat-induced insolubility were performed for functional and stability measurement assessment of immunoaffinity purified HSA, respectively. The optimum titer of anti-HSA determined by indirect ELISA was 256000. The SDS-PAGE showed that the purity rate of albumin was approximately 98% and WB confirmed the HSA functionality. Also, the heat-induced insolubility of immunoaffinity purified HSA was the same as the commercial HSA. Affinity chromatography using produced polyclonal antibody would be a robust method for purification of HSA.

Alpha 1-antitrypsin activity is markedly decreased in Wegener's granulomatosis.

Alpha 1-antitrypsin (A1AT) is the most abundant proteinase inhibitor in plasma and the main inhibitor of Proteinase 3, the target antigen of antineutrophil cytoplasmic antibodies (ANCAs) that predominant in Wegeners' granulomatosis. Α1AT deficiency correlated with ANCA-associated vasculitis. This study explores the trypsin inhibitory capacity (TIC), specific activity, and phenotypic deficiency of Α1AT in Wegener's granulomatosis. Twenty-seven WG patients were studied. ANCA was tested by IIF and ELISA. Serum a1-anti-trypsin levels were quantified in WG patients and healthy controls by immunoturbidimetric assay. Serum TIC was assessed by the enzymatic colorimetric assay. Phenotypes of A1AT were detected by Isoelectric Focusing. A1AT concentration was equivalent in patients and controls; however, serum TIC (P = 0.001) and specific activity of A1AT (P = 0.001) were dramatically lower in WG patients. Five patients had deficient phenotypes of A1AT: MZ (n = 3), MS (n = 1) and SS (n = 1). This was correlated with an increase in the prevalence of deficient phenotypes of A1AT in WG (P = 0.01). Trypsin inhibitory capacity and specific activity of A1AT were decreased in WG patients and may be involve in disease pathogenesis and can worsen the clinical manifestations. This A1AT deficiency probably resulted from oxidative inactivation and/or enzymatic degradation of A1AT. This could result in localized deficiency of A1AT in vessel wall interfaces and lead to severe disease.

Biomarkers for Diabetic Nephropathy with a Focus on Kidney Injury Molecule-1 (KIM-1).

Diabetic Nephropathy (DN), with an increasing rate of mortality and morbidity, is considered the main cause of End-Stage Renal Disease (ESRD). A wide spectrum of biomarkers exist for early detection of DN, but they suffer from low specificity and sensitivity, indicating the urgent demand for finding more effective biomarkers. Also, the pathophysiology of tubular damage and its relation to DN are not yet completely understood. Kidney Injury Molecule-1 (KIM-1) is a protein that is expressed at substantially low contents in the kidney under physiological conditions. A number of reports have demonstrated the close relationship between urine and tissue KIM-1 levels and kidney disorders. KIM-1 is known as a biomarker for diabetic nephropathy and renal injury. In this study, we aim to review the potential clinical and pathological roles of KIM-1 in diabetic nephropathy.

Mitochondria-loaded alginate-based hydrogel accelerated angiogenesis in a rat model of acute myocardial infarction.

Here, mitochondria were isolated from mesenchymal stem cells (MSCs) after being treated with mitochondria-stimulating substrates, 50 µM metformin (Met), and 40 µM dichloroacetic acid (DCA). The isolated mitochondria (2 × 107 particles) were characterized and encapsulated inside 100 µl hydrogel composed of alginate (3 % w/v; Alg)/gelatin (Gel; 1 % w/v) enriched with 1 µM pyrrole (Pyr) solidified in the presence of 0.2 M FeCl3. The physicochemical properties and cytocompatibility of prepared hydrogels were assessed using FTIR, swelling, biodegradation, porosity assays, and scanning electron microscopy (SEM). The mitochondria-bearing hydrogel was injected into the ischemic area of rat hearts. FTIR absorption bands represented that the addition of FeCl3 led to polypyrrole (PPy) formation, polysaccharide oxidation, and interaction between Alg and Gel. SEM images exhibited porous structure and the size of pores was reduced in Alg/Gel + PPy group compared to Alg + PPy hydrogel. Based on the data, both Alg + PPy and Alg/Gel + PPy hydrogels can preserve the integrity and morphology of loaded mitochondria. It was noted that Alg/Gel + PPy hydrogel possessed a higher swelling ratio, degradation, and porosity compared to Alg + PPy group. Data confirmed that Alg/Gel + PPy hydrogel containing 1 µM Pyr yielded the highest survival rate compared to groups with 2 and 4 µM Pyr (p < 0.05). Injection of mitochondria-loaded Alg/Gel + PPy hydrogel yielded significant restoration of left ventricle thickness compared to the infarction, mitochondria, and Alg/Gel + PPy hydrogel groups 14 days post-injection (p < 0.05). Histological analyses revealed a significant increase of vWF+ capillaries and α-SMA+ arterioles in the mitochondria-loaded Alg/Gel + PPy hydrogel group (p < 0.05). Immunofluorescence imaging revealed the ability of rat cardiomyocytes to uptake mitochondria alone or after being loaded into Alg/Gel + PPy hydrogel. These effects were evident in the Alg/Gel + PPy group. Taken together, electroconductive Alg-based hydrogels are suitable platforms for the transplantation of cells and organelles and the regeneration of ischemic heart changes.

Electrochemical microfluidic paper-based analytical devices for cancer biomarker detection: From 2D to 3D sensing systems.

Microfluidic paper-based analytical devices (µPADs) offer a unique possibility for a cost-effective portable and rapid detection of a wide range of small molecules and macromolecules and even microorganisms. In this line, electrochemical detection methods are key techniques for the qualitative analysis of different types of ligands. The electrochemical sensing µPADs have been devised for the rapid, accurate, and quantitative detection of oncomarkers through two-/three-dimensional (2D/3D) approaches. The 2D µPADs were first developed and then transformed into 3D systems via folding and/or twisting of paper. The microfluidic channels and connections were created within the layers of paper. Based on the fabrication methods, 3D µPADs can be classified into origami and stacking devices. Various fabrication methods and materials have been used to create hydrophilic channels in µPADs, among which the wax printing technique is the most common method in fabricating µPADs. In this review, we discuss the fabrication and design strategies of µPADs, elaborate on their detection modes, and highlight their applications in affinity-based electrochemical µPADs methods for the detection of oncomarkers.

Association of self-reported passive smoking in pregnant women with cotinine level of maternal urine and umbilical cord blood at delivery.

Passive smoking during pregnancy leads to adverse effects on mother and infant. The present investigation was designed to evaluate the association between maternal reported passive smoking with the cotinine concentration of maternal urine and umbilical cord blood at delivery and to determine the accuracy of maternal reporting of exposure to cigarette smoke during pregnancy. This was a cross-sectional study. From the 108 non-smoker pregnant women who were referred for delivery, 54 were passive smokers. Urine samples were collected from the mothers in the delivery room and blood samples after birth were taken from the umbilical cord. Passive smoking was evaluated through questionnaire and cotinine level of urine and umbilical cord blood. The geometric mean cotinine concentration of the maternal urine and the umbilical cord serum were, respectively, 27.4 ± 29.96 ng/mL and 3.71 ± 1.22 ng/mL in the exposed group (P < 0.001) and 0.75 ± 2.29 and 0.40 ± 0.63 in the non-exposed group (P < 0.001). There was a statistically significant correlation between maternal urinary and umbilical cord serum level of cotinine (P < 0.001, r = 0.58). Significant associations were shown between maternal reports of exposure to cigarette smoking with cotinine level of urine (kappa = 96%) and umbilical cord (kappa = 98%) (P < 0.001). This study shows that the pregnant woman's report of passive smoking during pregnancy in Iran is accurate. The questionnaire is an appropriate method to evaluate smoke exposure and could replace cotinine measurement.

Osteogenic differentiation of adipose-derived stem cells on dihydroartemisinin electrospun nanofibers.

BACKGROUND: Adipose tissue-derived stem cells (ASCs) are promising candidate in stem cell therapies, and maintaining their stemness potential is vital to achieve effective treatment. Natural-based scaffolds have been recently attracted increasing attention in nanomedicine and drug delivery. In this study, Dihydroartemisinin (DHART)-loaded polycaprolactone collagen nanofibers (PCL/Col NFs) were constructed as effective biocompatible scaffolds through adjusting the proportions of hydrophobic/ hydrophilic polymers for enhanced osteoblastic differentiation of human adipose-derived stem cells (hADSCs). RESULTS: The designed NFs were characterized through FTIR, XRD, TGA, FE-SEM, and tensile testing. DHART-loaded PCL/Col electrospun NFs provide an ideal solution, with the potential of sustained drug release as well as inhibition of drug re-crystallization. Interestingly, inhibiting DHART re-crystallization can improve its bioavailability and provide a more effective therapeutic efficacy. Besides, the data set found through FE-SEM, MTT, PicoGreen, qPCR, and alkaline phosphatase (ALP) assays revealed the improved adhesion and proliferation rate of hADSCs cultured on PCL/Col/DHART (5%) NFs after 14 and 21 days of incubation. CONCLUSIONS: These findings confirmed the potential of the designed NF scaffolds for sustained/controlled release of DHART therapeutic molecules toward bone tissue regeneration and engineering.

Reduction of secondhand smoke exposure among healthy infants in Iran: randomized controlled trial.

INTRODUCTION: The objective of this study was to assess whether counseling both mothers and fathers reduces their infants' exposure to secondhand smoke (SHS). METHODS: Participants were 130 nonsmoking children aged less than 1 year, exposed to their fathers' or mothers' smoking, and recruited from a health center in southern Tehran. Eligible families were randomly assigned to intervention or control group. Infant urine samples were collected, and parents were interviewed at baseline and at a 3-month follow-up in each of the 2 groups. Mothers of the intervention group were provided 3 counseling sessions, one of which was face to face and 2 of which were by telephone. Fathers were provided 3 counseling sessions by telephone. Parents were also given an educational pamphlet and a sticker depicting a smoke-free home. The control group received usual care. Changes in infant urinary cotinine levels, parental cigarette consumption in the presence of the child, and home- and car-smoking bans were assessed. RESULTS: The intervention was effective in reducing infant urinary cotinine levels (1-tailed p = .029). There was a greater decrease in the total daily cigarette consumption in the presence of the child in the intervention group compared with the control group, and the differences between the 2 groups were statistically significant (1-tailed p = .03). While the differences between home-smoking bans in the 2 groups were statistically significant (1-tailed p = .049), the differences between car-smoking bans did not reach significance. CONCLUSION: Counseling similar to that employed in other countries can reduce infant exposure to SHS, suggesting generalizability.

Vanillic Acid and Non-Alcoholic Fatty Liver Disease: A Focus on AMPK in Adipose and Liver Tissues.

Non-alcoholic fatty liver disease (NAFLD), a growing health issue around the world, is defined as the presence of steatosis in the liver without any other detectable byproducts such as alcohol consumption, which includes a wide spectrum of pathologies, such as steatohepatitis, cirrhosis, and hepatocellular carcinoma. A growing body of evidence indicates that the reduction in the 5' adenosine monophosphate-activated protein kinase (AMPK) activity, which could be activated by the consumption of the drugs, hormones, cytokines, and dietary restriction, is related to some metabolic disorders such as obesity, diabetes, PCOS, and NAFLD. Vanillic acid (VA), as an anti-inflammatory, anti-oxidative, anti-angiogenic and anti-metastatic factor, has protective effects on the liver as in two animal models of liver damage, it reduces serum levels of transaminases, inflammatory cytokines, and the accumulation of collagen in the liver and also prevents liver fibrosis. Besides, it decreases body and adipose tissue weight in a mice model of obesity and, similar to the liver tissue, diminishes adipogenesis through the activation of AMPK. It has been reported that VA can target almost all of the metabolic abnormalities of NAFLD, such as hepatic steatosis, inflammation, and hepatic injury, at least partially through the activation of AMPK. Therefore, in this review, we will discuss the possible and hypothetical roles of VA in NAFLD, with a special focus on AMPK.

Serum lipid profile of Parkinson's disease patients: A study from the Northwest of Iran.

BACKGROUND: Parkinson's disease (PD) is defined as a long-lasting, neurological illness. Low levels of serum lipid fractions are related with a high risk of PD. Current investigation was designed to evaluate the concentration blood lipid fractions in patients suffering from PD and compared with healthy subjects. METHODS: This case-control study was conducted from February 2016 to September 2018 in Tabriz University of Medical Sciences, Tabriz, Iran. The present investigation consisted of 75 persons who had PD and 75 normal people. The blood levels of lipid fractions were measured by concentrations of total cholesterol (TC), serum triglycerides (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), and total cholesterol. The results were analyzed with SPSS software using Kolmogorov-Smirnov, chi-square, and student's t-test. RESULTS: Serum level of TG was remarkably lower in patients with PD (111.92±8.75 mg/dL) compared with healthy subjects (123.64±9.97 mg/dL, P=0.008). Furthermore, we saw an important difference in the level of LDL-C (P=0.001) and TC (P=0.004) between the two groups. However, there was not any observed meaningful difference in the serum concentrations of HDL-C between the studied groups (P=0.135). CONCLUSION: Our results showed that the serum concentration of TG, LDL-C, and TC are noticeably lower in the PD suffering patients. Further investigations are needed to provide comprehensive information on the participants' cognitive layout and subsequent actions.

Different expression of Micro RNA-126, 133a and 145 in aorta and saphenous vein samples of patients undergoing coronary artery bypass graft surgery.

Introduction: microRNAs (miRNAs) are highly conserved, noncoding RNA molecules that regulate gene expression on the post-transcriptional level. Some evidence indicates that microRNAs dysfunction plays a crucial role in human disease development. The role of microRNAs in cardiac growth, hypertrophy, heart failure, cardiovascular complications in diabetes and many other hearth conditions are demonstrated. In this study we aimed to evaluate the expression of six microRNAs (mir-100, mir-126, mir-127, mir-133a, mir-133b and mir-145) that have been shown to overexpress in aortic and carotid plaques. Methods: Thirty Coronary Artery Disease patients who underwent elective coronary artery bypass graft surgery were enrolled in the study. The expression patterns of six miRNAs (mir-100, mir-126, mir-127, mir-133a, mir-133b, and mir-145) were examined in 30 patients of whom we obtained aorta and saphenous vein samples. Results: In three miRNAs, mir-100, mir-127 and mir-133b, we did not obtain expression data from real-time experiments. We found that the expression level of mir-126, mir-133a and mir145 were lower in aorta in comparison with saphenous vein. Mir-126 was highly expressed in saphenous vein samples (13.8±1.1) when compared with aorta samples (20.2±1.1), although mir133a was highly expressed in saphenous vein samples (16.1±0.5) when compared with the aorta (17.9±1.5). Expression of mir-145 saphenous vein samples was also dramatically higher than aorta (7.2±0.5 versus 10.8±0.6) that was statistically significant (P<0.05). Conclusion: Understanding the role of miRNAs in cardiovascular physiology and diseases might suggest miRNA- based therapeutic methods in the management of coronary artery disease.

Combination of metformin and phenformin synergistically inhibits proliferation and hTERT expression in human breast cancer cells.

OBJECTIVES: Breast cancer remains a global challenge, and further chemopreventive therapies are still immediately required. Emerging evidence has revealed the potent anti-cancer effects of biguanides, Metformin (MET) and phenformin (PHE). Thus, to explore an efficient chemopreventive strategy for breast cancer, the antiproliferative effects of the combination of MET and PHE against breast cancer cells were assessed. MATERIALS AND METHODS: Cytotoxicity of the drugs individually and in combination against T47D and MDA-MB-231 breast cancer cells were assessed using MTT assay and the median-effect method was used to analyze the precise nature of the interaction between MET and PHE. Besides, the expression levels of hTERT after 48 hr drug exposure were determined using qRT-PCR. RESULTS: Based on the cytotoxicity assay, both MET and PHE further inhibited the growth of MDA-MB-231 cells compared with T47D cells. It was found that MET+PHE reduced the IC50s of MET and PHE in both cells drastically more than the single treatments in a synergistic manner. Importantly, MET+PHE showed higher antiproliferative effect with smaller IC50 values against MDA-MB-231 cells than against T47D cells. Real-time PCR results revealed that hTERT expression was significantly reduced in both breast cancer cell lines treated with MET+PHE than the single treatments. In comparison between two types of breast cancer cells, it was detected that MET+PHE could further decline hTERT expression in MDA-MB-231cells than in T47D cells (P<0.001). CONCLUSION: It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.

Serum Levels of Vaspin and Its Correlation with Nitric Oxide in Type 2 Diabetic Patients with Nephropathy.

BACKGROUND: Diabetic Nephropathy (DN), a serious and prevalent complication of diabetes, has been rapidly raising worldwide. Vaspin, as an adipokine with anti-diabetic effects, is predominantly released from visceral adipose tissue. Moreover, vaspin has the stimulatory effect on nitric oxide (NO) bioavailability through the activation of NO synthase. OBJECTIVE: The aim of the present study was to investigate the serum levels of vaspin and their correlation with NO metabolite in diabetic patients with normal renal function and renal insufficiency. METHODS: Volunteers patients with non-nephropathy Type 2 Diabetic Mellitus (T2DM) as control (n=40, age= 56.95±6.11 years) and patients with diabetic nephropathy (DN) (n=40, age=57.85±5.63 years) as case group were enrolled in this study, and serum samples were collected for the measurement of vaspin levels by ELISA technique. Also, serum levels of NO metabolites were calorimetrically assessed. RESULTS: We found that vaspin levels significantly decreased in diabetic patients with nephropathic condition as compared with diabetic patients with normal renal function (p <0.04). In addition, serum levels of NO metabolites were significantly higher in diabetic patients with nephropathy in comparison with non-nephropathic diabetics (p<0.001). When patients with DN were studied, vaspin levels positively correlated with NO metabolites and Homeostasis model assessment of insulin resistance (HOMA-IR) levels. CONCLUSION: This study showed that low serum vaspin levels may be a risk factor for nephropathy in type II diabetic patients and increased levels of NO may be a defensive mechanism in the DN.

Association Between Matrix Metalloproteinase-3 Activity and Glomerular Filtration Rate and Albuminuria Status in Patients With Type 2 Diabetes Mellitus.

INTRODUCTION: Diabetic nephropathy is pictured as matrix accumulation and thickening of glomerular basal membrane. Matrix metalloproteinases (MMPs) are major proteases involved in extracellular matrix degradation. Moreover, plasminogen activator inhibitor-1 (PAI-1) primarily regulates plasmin dependent proteolysis. It plays a role in renal fibrosis causing extracellular matrix accumulation through inhibition of plasmin-dependent extracellular matrix degradation. This study investigated PAI-1 serum level and MMP-3 activity and their correlation with glomerular filtration rate in patients with diabetes mellitus. MATERIALS AND METHODS: In a case-control design, serum PAI-1 concentrations and MMP-3 activity were measured in 80 patients with normoalbuminuria, microalbuminuria, and macroalbuminuria. Receiver operating characteristics curve analysis was used to assess the diagnostic accuracy of MMP-3 activity in discriminating albuminuria. RESULTS: In the patients with microalbuminuria, serum PAI-1 levels were higher compared with macroalbuminuric patients (P < .001). The patients with macroalbuminuria exhibited a significantly lower MMP-3 activity than the patients with microalbuminuria and normoalbuminuria (P < .001). No significant correlation was found between serum MMP-3 activity and serum PAI-1 levels in those with normoalbuminuria, microalbuminuria, and macroalbuminuria. The MMP-3 activity had a strong positive correlation with estimated glomerular filtration (r = 0.853, P < .001). CONCLUSIONS: We found that there was a positive correlation between glomerular filtration rate and MMP-3 activity in diabetic patients. This concludes that MMP-3 may have a role in the pathogenesis of diabetic nephropathy progressions towards macroalbuminuria, and therefore, MMP-3 activity may be used in evaluating albuminuria status.

Correlation Between Circulating Visfatin and Nitric Oxide Metabolites Levels in Patients With Diabetic Nephropathy.

INTRODUCTION: Diabetic nephropathy is one of the serious complications of diabetes mellitus. Visfatin is an intracellular enzyme with insulin-mimicking effects. It enhances the expression of endothelial nitric oxide (NO) synthase in renal cells. This study aimed to investigate serum levels of visfatin and NO metabolites in patients with diabetic nephropathy. MATERIALS AND METHODS: A total of 80 diabetic patients were enrolled and classified into nephropathic and non-nephropathic patients. Serum visfatin and insulin levels were estimated using an enzyme-linked immunosorbent assay, and NO metabolites were estimated using a colorimetric assay. RESULTS: Serum visfatin and NO metabolites levels were significantly elevated in the patients with diabetic nephropathy. Serum visfatin levels and NO metabolites were significantly higher in the nephropathic patients (P = .003; 95% confidence interval, 2.29 to 10.81; P < .001; 95% confidence interval, 3.14 to 9.46, respectively) as compared to the control group, whereas homeostatic model assessment-insulin resistance was significantly lower (P = .02; 95% confidence interval, -1.51 to -1.01).There was no correlation between body mass index, blood pressure, lipid profile, insulin, and glucose levels and serum visfatin and NO metabolites levels. CONCLUSIONS: The results of this study demonstrated that there were high levels of visfatin and NO metabolites in patients with diabetic nephropathy. In addition, there was a positive correlation between visfatin and NO metabolites levels in nephropathic and non-nephropathic diabetic patients.

Dysregulation of serum NADPH oxidase1 and ferritin levels provides insights into diagnosis of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a common neurodegenerative disease. Oxidative stress is considered as a key modulator in the development of PD. This study aimed to investigate associations between serum NOX1 (NADPH oxidase1), ferritin, selenium (Se), and uric acid (UA) levels and clinical parameters in patients with PD. DESIGN AND METHODS: Serum levels of NOX1, ferritin, Se, and UA were measured in 40 PD patients and 40 healthy individuals. Receiver operating characteristic (ROC) analysis was performed to investigate incremental diagnostic value of each factor in the study groups. RESULTS: Mean serum NOX1 levels were markedly higher in patient group (22.36±5.80ng/mL) versus healthy individuals (8.89±2.37ng/mL) (p<0.001). Significant differences were also observed in the serum concentrations of ferritin (p=0.005) and Se (p=0.001) between patients with PD and healthy individuals. However, the serum concentrations of UA were not statistically significant between the study groups (p=0.560). ROC analysis revealed a diagnostic ability of serum NOX1 and ferritin levels for PD with an area under ROC curve of ≥0.7 (p<0.05) and relatively high sensitivity and specificity. Combination of serum NOX1 and Se along with ferritin and UA levels increased the sensitivity up to 85%, specificity up to 97% and area under the ROC curve up to 0.94 (95% confidence interval (95% CI): 0.89 to 0.99, p<0.001). CONCLUSION: Our findings indicated that serum concentrations of NOX1, ferritin, and Se are significantly higher in the patients with PD. Therefore, these factors can be considered as potential diagnostic biomarkers for diagnosis and monitoring of PD patients. Further studies are required with larger sample size to provide more detailed information about the cognitive profile of participants and the outcome measures.