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Colorectal cancer is the third most common cancer globally. Despite extensive preclinical and clinical studies, it is still among the leading causes of cancer-related death, and a need for new therapeutic options is required. The renin-angiotensin system plays an important role in regulating blood pressure and cell growth. In addition to their hemodynamic effects, some of the renin-angiotensin system components, such as angiotensin, are also growth factors that promote cell proliferation and angiogenesis, and its dysregulation is reported to be associated with poor prognosis in colorectal cancer. Here we describe the critical role of the renin-angiotensin system pathway in colorectal cancer as well as the preclinical and clinical investigations renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as a potential therapeutic target in the treatment of colorectal cancer. Several studies have been shown that the inhibition of these pathways can reduce tumor growth and metastasis; however, some of the data remain inconsistent. There is accumulating evidence of the therapeutic potential of some inhibitors, such as Losartan which are now in clinical phases in the treatment of several malignancies using Nivolumab in combination with FOLFIRINOX in pancreatic cancer. Further investigations are warranted to improve the efficacy and selectivity of current and future anticancer strategies targeting renin-angiotensin systems., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Colorectal cancer (CRC) is an important cause of cancer-related mortality. Aberrant activation of the renin-angiotensin system (RAS) is reported to be associated with poor clinical outcomes in patients with CRC. This study was designed to explore the anti-tumor effects of the angiotensin receptor blocker Candesartan either alone or in combination with 5-FU in in vitro and in vivo models of CRC. The cytotoxic effects of Candesartan were assessed using the MTT assay in two colorectal cancer cell lines (CT-26 and SW-480). To investigate the potential regulatory role of Candesartan on tumor growth, apoptosis, and migration, the expression levels of Cyclin D1, Survivin, MMP3, MMP9, and E-cadherin mRNAs were evaluated. The oxidant/antioxidant balance was also examined by determining the levels of MDA, thiols, SOD, and CAT. We used a xenograft model of colon cancer to investigate the effects of Candesartan alone, or in combination with 5-FU, on tumor growth following histological staining (Hematoxylin & Eosin and Masson trichrome staining) and biochemical studies as well as gene expression analyses by RT-PCR and western blotting. Candesartan suppressed tumor cell proliferation and migration by modulating Cyclin D1, MMP3/9, and E-cadherin. Treatment with Candesartan either alone, or in combination with 5-FU decreased tumor size in the mouse model, and also increased the level of oxidative markers MDA and reduced CAT, SOD, and thiols. Histological evaluation showed that Candesartan increased tumor necrosis, reduced tumor density and attenuated collagen deposition reducing tumor fibrosis in tumor xenograft. Candesartan, an inhibitor of the RAS, when used in combination with 5-FU reduced tumor growth by inhibiting fibrosis and inducing ROS production, supporting further clinical studies on this therapeutic approach for treatment of CRC., (Copyright © 2021 Tabatabai et al.)

Background: Abdominal adhesions are common and often develop after abdominal surgery. There are currently no useful targeted pharmacotherapies for adhesive disease. Saffron and its active constituents, Crocin and Crocetin, are wildly used in traditional medicine for alleviating the severity of inflammatory or malignant disease., Purpose: The aim of this study was to investigate the therapeutic potential of the pharmacological active component of saffron in attenuating the formation of post-operative adhesion bands using different administration methods in a murine model., Material Method: saffron extract (100 mg/kg), Crocin (100 mg/kg), and Crocetin (100 mg/kg) were administered intraperitoneally and by gavage in various groups of male Wistar rat post-surgery. Also three groups were first treated intra-peritoneally by saffron extract, Crocin, and Crocetin (100 mg/kg) for 10 days and then had surgery. At the end of the experiments, animals sacrificed for biological assessment., Result: A hydro-alcoholic extract of saffron and crocin but not crocetin potently reduced the adhesion band frequency in treatment and pre-treatment groups in the mice given intra-peritoneal (i.p) injections. Following the saffron or crocin administration, histological evaluation and quantitative analysis represented less inflammatory cell infiltration and less collagen composition, compared to control group. Moreover, the oxidative stress was significantly reduced in treatment groups., Conclusion: These findings suggest that a hydro-alcoholic extract of saffron or its active compound, crocin, is a potentially novel therapeutic strategy for the prevention of adhesions formation and might be used as beneficial anti-inflammatory or anti-fibrosis agents in clinical trials., Taxonomy: Abdominal surgeries/post-surgical adhesions., Competing Interests: The authors have no conflicts of interest., (© 2021 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Aim and Objective: Diabetes mellitus is associated with inflammation and increased oxidative stress. In the current study, we aimed to investigate the relationship between type 2 diabetes mellitus (T2DM) and serum pro-oxidant-antioxidant balance (PAB) in a large populationbased study., Methods: In this cross-sectional study, 7888 individuals were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. Participants were divided into three groups based on their serum PAB values (levels < 36.4, 36.4-82.6 and > 82.6 HK). Serum PAB values were measured using a colorimetric method and enzyme-linked immune sorbent assay (ELISA)., Results: Serum PAB in subjects with and without diabetes was reported 76.85 ± 61.07 HK and 69.51 ± 55.50 HK. In subjects with a serum PAB > 82.6 HK the risk of T2DM was 1.2 fold higher in comparison to subjects with a serum PAB < 36.4 HK (OR: 1.26, 95% CI: 1.09 - 1.47, P-value: 0.002). This association remained significant after adjustment for confounding factors in multivariable analysis (OR: 1.19, 95% CI: 1.02 - 1.38, P-value: 0.027)., Conclusion: Increased pro-oxidant levels may be a major complication of T2DM in our study subjects and PAB could be an indicator of higher oxidative stress in T2DM patients from northeastern Iran., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: Rigosertib (RGS) is a PI3K inhibitor that exerts protective effects against tumor progression and cancer-related inflammation. This study was aimed to explore the regulatory effects of RGS on proliferative, pro-fibrotic and inflammatory factors in DSS- induced colitis mice model., Materials and Methods: The present study integrates systems and molecular biology approaches to investigate the therapeutic potency of RGS in an experimental model of colitis specifically examining its effects on the PI3K/AKT and NF-κB signaling pathways., Key Findings: Analysis of time-resolved proteome profiling showed that PI3K-AKT inhibitors regulate expression of many proteins in all stages of inflammation, fibrogenesis and extracellular matrix remodeling. Consistent with our in-silico findings, RGS improved colitis disease activity as assessed by changes in body weight, degree of stool consistency, rectal bleeding and prolapse. RGS also reduced oxidative stress markers and colon histopathological score by decreasing inflammatory responses in colon tissues. Moreover, expression of pro-fibrotic and pro-inflammatory factors including Acta 2, Col 1a1, Col 1a2, IL-1β, TNF-α, INF-γ, and MCP-1 were suppressed in the mice treated with RGS compared to the control group. The protective effects of RGS were mediated by inactivation of PI3K/AKT and NF-kB signaling pathways., Significance: This study clearly demonstrates the anti-proliferative, anti-inflammatory and anti-fibrotic effects of RGS in colitis that may have implications for the treatment of colitis and colitis-associated cancer., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Here, we have investigated the therapeutic potency of EW-7197, a transforming growth factor-β type I receptor kinase inhibitor, against postsurgical adhesion band formation. Our results showed that this pharmacological inhibitor prevented the frequency and the stability of adhesion bands in mice model. We have also shown that downregulation of proinflammatory cytokines, reduce submucosal edema, attenuation of proinflammatory cell infiltration, inhibition of oxidative stress, decrease in excessive collagen deposition, and suppression of profibrotic genes at the site of surgery are some of the mechanisms by which EW-7197 elicits its protective responses against adhesion band formation. These results clearly suggest that EW-7197 has novel therapeutic properties against postsurgical adhesion band formation with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in postsurgery patients., (© 2019 Wiley Periodicals, Inc.)

Tumor cell invasion and metastasis are the definitive cause of mortality in breast cancer (BC). Hypoxia and pro-inflammatory cytokines upregulate the CD73 gene in the tumor microenvironment. Subsequently, CD73 triggers molecular and cellular signaling pathways by both enzymatic and nonenzymatic pathways, which finally leads to breast tumor progression and development. In this paper, we summarize current advances in the understanding of CD73-driven mechanisms that promote BC development and mortality. Furthermore, we evaluate the therapeutic potential of CD73 targeting in BC., (© 2019 Wiley Periodicals, Inc.)

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Until recently, it was thought that myocardium was not able to repair itself, but studies have now shown that resident cardiac stem cells have regenerative capacity, and stem cell therapy may be a novel approach for cardiac muscle repair and regeneration. Stem cell-derived paracrine factors have been shown to regulate ventricular remodeling, inflammation, apoptosis, cardiomyocytes regeneration, and neovascularization in regions of infarcted cardiac tissue. In this review, we summarize the evidence from cellular, animal, and clinical studies supporting the potential clinical significance of stem cell therapy as a novel therapeutic approach for the treatment of MI., (© 2019 Wiley Periodicals, Inc.)

EW-7197 is a transforming growth factor-β type I receptor kinase inhibitor with potential anti-inflammatory and antifibrotic properties. Here, we investigate the potential therapeutic effects of EW-7197 in a murine model of ulcerative colitis. EW-7197 attenuated the colitis disease activity index by improving rectal bleeding, body weight, and degree of stool consistency. EW-7197 also reduced colorectal tissue damage and the colon histopathological score by reducing crypt loss, mucosal damage, and tissue inflammation. Moreover, EW-7197 appeared to ameliorate the inflammatory and fibrotic responses by reducing oxidative stress, reducing submucosal edema and inflammatory cell infiltration, downregulating proinflammatory and pro-fibrotic genes, and inhibiting excessive collagen deposition in inflamed and fibrotic ulcerative colitis tissues. These results suggest that EW-7197 has potentially useful therapeutic properties against colitis, with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in patients with colitis., (© 2018 Wiley Periodicals, Inc.)

The red blood cell distribution width (RDW) is an index of the heterogeneity of circulating red blood cell size, which along with other standard complete blood count (CBC) parameters are used to identify hematological system diseases. Besides hematological disorders, several clinical studies have shown that an increased in the RDW may be associated with other diseases including acute pancreatitis, chronic kidney disease, gastrointestinal disorders, cancer, and of special interest in this review, cardiovascular disease (CVD). The diagnostic and prognostic value of RDW in different CVD (acute coronary syndrome, ischemic cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and acute ischemic stroke) has been reviewed in this article, to provide an understanding how its measurement may be applied to improve the management of these conditions., (© 2019 International Union of Biochemistry and Molecular Biology.)

Copeptin is a glycosylated peptide derived from the cleavage of the precursor of arginine-vasopressin. In contrast to arginine-vasopressin, copeptin is a stable molecule and can easily be measured using a simple rapid assay. The serum concentration of copeptin is increased in several clinical conditions, including hypertension, chronic kidney disease, and, of special interest in this review, in cardiovascular diseases. The diagnostic and prognostic value of copeptin in different cardiovascular diseases (acute coronary syndrome, stable coronary artery disease, congestive heart failure, and acute ischemic stroke) has been reviewed in this article, to provide an understanding of how its measurement may be applied to improve the management of these conditions., (© 2018 Wiley Periodicals, Inc.)

Background: Gamma glutamyl transferase (GGT) is associated with pathogenesis of various diseases such as coronary artery disease (CAD). GGT activity displays an essential role in the catabolism of glutathione which is reported as a major antioxidant. The aim of this study was to explore the association of GGT activity with obstruction severity of artery in 500 CAD patients., Results: Our finding showed a significant association between serum GGT activity and CAD patients. In particular, the level of GGT in patients who had ≥50% obstruction was higher, compared to healthy and patients with less than 50% obstruction in their coronary arteries (the level of GGT in patients with at least one (1 SVD), two (2VD), three (3VD) coronary artery obstruction were 55.6±9.7, 71.7±12.7 and 84.7±13.4, while these values in patients with negative angio or control group were 28±10 and 17±4.6). Furthermore, the activity of this marker was associated with increased the risk of CAD (Odd ratio of GGT in 3VD group: 2, 95%CI: 1.8-2.3), which was also related with HDL-C. Of note, the level of GGT was enhanced progressively with increasing the obstruction severity of arteries., Conclusion: We demonstrate the prognostic value of serum level of GGT as a biomarker for predicting obstruction severity in patients with CAD., (Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Combination of dyslipidemic phenotypes, including elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), elevated plasma triglycerides (TG), and decreased low-density lipoprotein cholesterol (HDL-C) concentrations, is important because of the association of individual phenotypes with increased risk of cardiovascular disease (CVD). We investigated the prevalence of combined dyslipidemias and their effects on CVD risk in an Iranian large population., Method: A total of 9847 individuals were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. Anthropometric parameters and biochemical indices were measured in all of the subjects. Different types of combined dyslipidemias including high TG + low HDL-C, high TG + low HDL-C + high LDL-C, low HDL-C + high LDL-C, high TG + high LDL-C, and finally high TG + high LDL-C + low HDL-C were considered. Ten-year CVD risk was calculated using the QRISK2 risk algorithm and adjustments were made as suggested by the Joint British Societies' (JBS2). Logistic regression analyses were performed to determine the association between different combined dyslipidemias and categorical QRISK., Results: A total of 3952 males and 5895 females were included in this current study. Among the included subjects, 83.4% had one form of dyslipidemia, and 16.6% subjects were not dyslipidemic. The mean age was 48.88 ± 7.9 and 47.02 ± 8.54 years for dyslipidemic and nondyslipidemic groups, respectively. The results showed that the frequency of dyslipidemia was 98%, 87.1%, and 90% in subjects with metabolic syndrome, CVD, and diabetes, respectively. Our results suggested that around 15.7% of study population were at 10 years CVD risk (high ≥20) and it was higher in men than women (P < .001). Moreover, risk of CVD was higher in TG↑ & HDL↓ & LDL↑ group than other groups., Conclusion: Prevalence of dyslipidemia was 83.4% among Iranian adults. The results showed that individuals with increased plasma TG and LDL-C, and low HDL-C levels had the highest 10 years CVD risk compared to other combined dyslipidemic phenotypes., (© 2018 Wiley Periodicals, Inc.)

There is persuasive evidence that oxidative stress and inflammation are features of the metabolic syndrome (MetS). We have investigated the relationship between serum pro-oxidant-antioxidant balance (PAB), serum uric acid, and high sensitive C-reactive protein (hs-CRP) in 7,208 participants from the MASHAD study cohort, who were categorized as having MetS, or not, using International Diabetes Foundation (IDF) criteria. Serum hs-CRP was measured by Polyethylene glycol (PEG)-enhanced immunoturbidimetry method using an Alycon analyzer (ABBOTT, Chicago, IL, USA). A colorimetric method was used to determine serum PAB. Serum PAB values were significantly higher in the individuals with MetS compared to those without (P < 0.001). Furthermore, there was a step-wise increase in mean serum PAB concentrations as the number of components of the MetS increased. The combination of features of MetS had different association with serum PAB and hs-CRP. Multiple linear regression analysis showed that body mass index (BMI, B = 2.04, P < 0.001), physical activity level (PAL, B = 18.728, P = 0.001), serum uric acid (B = -1.545, P = 0.003), and serum C-reactive protein (B = 0.663, P < 0.001) were associated with serum PAB in individuals with MetS. Multiple logistic regression analysis showed that serum PAB (B = 0.002, P < 0.001, CI = 1.001-1.003), serum C-reactive protein (B = 0.007, P < 0.015, CI = 1.001-1.013), and serum uric acid (B = 0.207, P < 0.001, CI = 1.186-1.277) were all significantly associated with MetS. Serum PAB was strongly associated with serum uric acid and serum hs-CRP. Moreover, serum PAB as well as serum uric acid and serum hs-CRP were independently associated with MetS. Individual features of MetS were also associated with serum hs-CRP and PAB. © 2018 BioFactors, 44(3):263-271, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

Extracellular concentration of adenosine increases in the hypoxic tumor microenvironment. Adenosine signaling regulates apoptosis, angiogenesis, metastasis, and immune suppression in cancer cells. Adenosine-induced cell responses depend upon different subtypes of adenosine receptors activation and type of cancer. Suppression of adenosine signaling via inhibition of adenosine receptors or adenosine generating enzymes including CD39 and CD73 on ovarian or cervical cancer cells is a potentially novel therapeutic approach for gynecological cancer patients. This review summarizes the role of adenosine in the pathogenesis of gynecological cancer for a better understanding and hence a better management of this disease., (© 2017 Wiley Periodicals, Inc.)

Background: Saffron, the dried stigmas of Crocus sativus L., is a highly valued agricultural product that is used mainly as a food coloring and flavoring agent. Three main secondary metabolites of Crocus sativus including crocin, picrocrocin, and safranal are responsible for the color, the bitter taste and for the odor and aroma, respectively. As a component of traditional medicine, saffron has been utilized as a medicinal herb for treating various ailments including cramps, asthma, liver disease, menstruation disorders, pain, and in the pathogenesis of cancer., Hypothesis/purpose: To summarize the recent published data on the chemo-preventive properties of Crocus sativus in cancer treatment., Study Design: We conducted a non-systematic review of the literature., Methods: A search of English-language literature was performed using Scopus, EMBASE and PubMed. We applied no restriction in time. Articles were searched using the keywords "Lung", "breast", "skin", "prostate", "leukemia", "cancer", "neoplasm", "tumor", "malignancy", "saffron", "crocus sativus", "crocin", "crocetin", "picrocrocin", and "safranal"., Results: Saffron has been reported to exert anti-tumor and anti-cancer effects in various types of cancer including lung cancer, breast cancer, leukemia, skin cancer and prostate cancer. This appears to be via various mechanisms including: the induction of apoptosis, arresting cell cycle progression, suppressing expression of matrix metalloproteinase, modulatory effects on some phase II detoxifying enzymes and decreasing expression of inflammatory molecules are potential mechanisms of saffron-induced anticancer effects., Conclusion: Saffron possesses potent anti-tumor properties and represents an efficacious and safe treatment., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The plasma level of adenosine increases under ischemic and inflamed conditions in tumor microenvironment. Adenosine elicits a range of signaling pathways in tumors, resulting in either inhibition or enhancement of tumor growth depending upon different subtypes of adenosine receptors activation and type of cancer. Metabolism of adenosine-5'-triphosphate (ATP) and its derivatives including adenosine is dysregulated in the breast tumor microenvironment, supporting the role of this metabolite in the pathogenesis of breast cancer. Adenosine regulates inflammation, apoptosis, cell proliferation, and metastasis in breast cancer cells. This review summarizes the role of adenosine in the pathogenesis of breast cancer for a better understanding and hence a better management of this disease., (© 2017 Wiley Periodicals, Inc.)

Saffron, the dried stigmas of Crocus sativus L., is mainly used as a food coloring and flavoring agent. This agricultural product is used in traditional medicine for the treatment of several diseases including asthma, liver disease, menstruation disorders, and, of special interest in this review, metabolic syndrome. Saffron and its active components including crocin, crocetin, and safranal are potential therapeutic candidates for attenuating MetS complications including hypertension, hyperglycemia, obesity, and dyslipidemia. This review summarizes the protective role of saffron and its constituents in the pathogenesis of MetS for a better understanding and hence a better management of this disease.

Background: Hypertension (HTN) is a risk factor for stroke, renal failure, and cardiovascular disease. The association between biochemical and hematological parameters with high blood pressure may provide a more precise approach to risk prediction conferred by HTN in these patients., Objective: The aim of current study was to explore whether biochemical and hematological parameters are associated with HTN in a cohort study with a 7-year follow-up., Materials and Methods: A total of 9808 individuals were enrolled and recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study, and biochemical and hematological factors were measured in all subjects. Univariate and multivariate logistic regression analysis were performed to determine the association of biochemical and hematological parameters with HTN., Results: Several biochemical parameters including fasting plasma glucose (FBG), serum high-sensitivity C-reactive protein (hs-CRP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and uric acid were increased in hypertensive participants. In contrast, serum high-density lipoprotein cholesterol (HDL-C) was lower in hypertensive individuals. Furthermore, we demonstrated that hematological parameters including white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB), hematocrit (HCT), and mean corpuscular hemoglobin (MCH) were higher in the hypertensive group compared to the control group. But mean corpuscular volume (MCV), and red cell distribution width (RDW), were decreased in the hypertensive group. Furthermore, our results strongly suggested that among these parameters, hematocrit was the independent risk factor for hypertension in the population., Conclusion: We demonstrated the association of altered biochemical and hematological factors with hypertension supporting the value of emerging markers for early prediction of high blood pressure in prone individuals., (© 2017 Wiley Periodicals, Inc.)

Background: Depression and anxiety are two common mood disorders that are both linked to systemic inflammation. Increased white blood cell (WBC) count and red cell distribution width (RDW) are associated with negative clinical outcomes in a wide variety of pathological conditions. WBC is a non-specific inflammatory marker and RDW is also strongly related to other inflammatory markers. Therefore, we proposed that there might be an association between these hematological inflammatory markers and depression/anxiety symptoms., Objective: The primary objective of this study was to examine the association between depression/anxiety symptoms and hematological inflammatory markers including WBC and RDW in a large population-based study., Methods: Symptoms of depression and anxiety and a complete blood count (CBC) were measured in 9274 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated using the Beck Depression and Anxiety Inventories., Results: The mean WBC count increased with increasing severity of symptoms of depression and anxiety among men. Male participants with severe depression had significantly higher values of RDW (p<0.001); however, this relationship was less marked among women (p=0.004). In addition, men (but not women) with severe anxiety symptoms had significantly higher values of RDW (p<0.001). Moreover, there was a negative association between red blood cell (RBC) and mean corpuscular hemoglobin (MCH) and symptoms of depression/anxiety., Conclusion: Our results suggest that higher depression and anxiety scores are associated with an enhanced inflammatory state, as assessed by higher hematological inflammatory markers including WBC and RDW, even after adjusting for potential confounders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Thrombin-induced activation of protease-activated receptors (PARs) represents a link between inflammation and cancer. Proinflammatory signaling functions of thrombin are associated with several inflammatory diseases including neurodegenerative, cardiovascular, and of special interest in this review cancer. Thrombin-induced inflammatory responses up-regulates expression of cytokines, adhesion molecules, angiogenic factors, and matrix-degrading proteases that facilitate tumor cells proliferation, angiogenesis, invasion, and metastasis. This review summarizes the current knowledge about the mechanisms of thrombin-mediated proinflammatory responses in cancer pathology for a better understanding and hence a better management of this disease., (© 2016 Wiley Periodicals, Inc.)

Background: Depression and anxiety are two important mood disorders that are frequently associated with chronic diseases such as cardiovascular diseases (CVDs). Hyper-inflammation is related to both CVDs and psychological conditions such as depression and anxiety. Therefore, inflammation may partially explain the relationship between depression and cardiovascular disease., Objective: The objective of this study was to perform a gender-stratified examination of the association between symptoms of depression/anxiety disorders and serum hs-CRP and inflammation linked conditions in a large Iranian population., Methods: Symptoms of depression and anxiety disorders and serum hs-CRP levels were measured in 9759 participants (40% males and 60% females) aged 35-65 years, enrolled in a population-based cohort (MASHAD) study in north-eastern Iran. Symptoms of depression and anxiety were evaluated with Beck Depression and Anxiety Inventories. According to the scores of depression and anxiety, individuals were categorized into four groups of no or minimal, low, moderate and severe categories., Results: The median serum hs-CRP concentration increased with increasing severity of depression and anxiety disorders. Male participants with severe depression had significantly higher levels of hs-CRP (p<0.001); however, this relationship was less marked among women (p=0.04). Subjects with severe anxiety also had significantly higher levels of hs-CRP (p<0.001). Moreover, women with severe depression and anxiety had higher BMI. There was also a positive association between current smoking habit and depression/anxiety disorders., Conclusion: Depression and anxiety disorders are associated with elevated levels of hs-CRP, particularly among men. Also, there is a significant positive association between depression/anxiety disorders and inflammation linked conditions such as smoking and obesity; however, in the case of obesity this association is only present in women., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Wnt5a initiates pro-inflammatory responses through activation of non-canonical Wnt signaling pathway. Pro-inflammatory functions of Wnt5a trigger pro-inflammatory signaling cascades and increase secretion of pro-inflammatory cytokines and chemokines. Wnt5a as a potent signaling molecule is strongly implicated in a number of diseases including cancer, diabetes, metabolic disorders, and of special interest in this review, inflammatory diseases. This review summarizes the role of Wnt5a in the pathogenesis of inflammatory diseases including atherosclerosis, rheumatoid arthritis, psoriasis vulgaris and sepsis, promoting greater understanding, and clinical management of these diseases. J. Cell. Physiol. 232: 1611-1616, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Thrombin initiates proinflammatory signaling responses through activation of protease-activated receptors (PARs) in in vitro and in vivo systems. Proinflammatory signaling function of thrombin increases secretion of proinflammatory cytokines and chemokines, triggers vascular permeability, promotes leukocyte migration, and induces adhesion molecule expression. Thrombin as a potent signaling molecule is strongly implicated in a number of proinflammatory disorders including severe sepsis, cancer, cardiovascular disease, and of special interest in this review neurodegenerative disorders. This review summarizes the role of thrombin in the pathogenesis of central nervous system (CNS) inflammatory diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), promoting greater understanding and clinical management of these diseases. J. Cell. Physiol. 232: 482-485, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background/objectives: Metabolic syndrome (MetS) is characterized by abdominal obesity, dyslipidemia, hypertension and glucose intolerance, and is associated with an increased risk of developing cardiovascular disease (CVD), diabetes mellitus and related diseases. Circulating levels of inflammatory markers such as C-reactive-protein (CRP) have reported to be associated with CVD. Against this background, the prevalence of MetS is increasing globally, and thus predictive biomarkers are required for identification of MetS patients at an increased risk. Here we explored the value of CRP as a biomarker in 7284 subjects and also investigated which features of MetS have the greatest association with the hs-CRP level., Subjects/methods: The subjects were recruited from the Mashhad stroke and heart atherosclerotic disorder study. Anthropometric factors and biochemical parameters (for example, high-sensitivity CRP (hs-CRP), high-density lipoprotein/low-density lipoprotein, triglycerides (TGs) and fasting blood glucose (FBG)) were determined. Univariate and multivariate analyses were conducted to evaluate the association of hs-CRP and MetS., Results: Our results illustrated that the concentration of serum hs-CRP increased progressively with the number of MetS components, and subjects who fulfilled the criteria of MetS for waist circumference, TGs, blood pressure and FBG were found to have hs-CRP of 0.53, 0.38, 0.34 and 0.71 mg/l, respectively, higher than matched-subjects. Importantly, FBG had the greatest association with hs-CRP concentration., Conclusions: Our data demonstrate the significant association between MetS components with hs-CRP, indicating that this association was cumulative by increasing the number of the defining features of MetS, supporting further studies to explore the value of emerging marker as a novel method for detecting individuals at high risk of developing MetS.

Purpose: We have investigated the association between markers of renal function [serum urea nitrogen, creatinine, and estimated glomerular filtration rate (eGFR)] and age and lipid profile in an Iranian population sample of 4,567 subjects., Materials/methods: Serum creatinine and urea nitrogen, together with anthropometric parameters and lipid profile were determined in all the subjects. eGFR was calculated using the modification of diet in renal disease formula., Results: Serum creatinine and urea nitrogen increased with age (p < .05), and this relationship was also more pronounced in men compared to women. Increased levels of these renal function markers were significantly associated with altered lipid profiles., Conclusion: Levels of renal function markers increased with age and were associated with altered lipid profile.

Objective: The global prevalence of metabolic syndrome (MetS) appears to be increasing and the impact of this condition on potential comorbidities such as cardiovascular disease is high. Chronic kidney disease (CKD) is also a potential comorbidity of MetS but the method of screening for this is somewhat controversial. Thus, predictive markers that can predict the risk of developing CKD are warranted for identification of patients with MetS at an increased risk., Research Methods/patients: We investigated the occurrence of CKD in 6492 individuals, either with or without MetS., Results: Our results showed that the prevalence of CKD was markedly higher in those individuals with MetS, and increased progressively with the number of MetS components and age. Waist circumference, triglycerides and high-density lipoprotein cholesterol were significantly (p<0.05) associated with altered levels of urea nitrogen, glomerular filtration rate and creatinine, and were related to the increased risk of CKD (eg, OR 1.293 (95% CI 1.10 to 1.52; p=0.002)). The relative risk of CKD remained statistically significant for uric acid following multivariate analyses and adjusting for MetS-associated factors., Conclusions: Our data demonstrated the association of MetS components with CKD in our population and revealed that susceptibility to CKD was increased with the number of defining features of MetS. These findings prompt prospective studies to determine the impact of preventing and detecting MetS on the risk of developing CKD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Rheumatoid arthritis (RA) is an autoimmune disease that tends to be progressive and chronic. Previous studies showed that oxidative stress has a main role in pathology of RA. The aim of this study was the easy elucidation of oxidative stress through pro-oxidant-antioxidant balance (PAB) in these patients., Method: The sera of 130 RA patients and 130 age-matched healthy subjects (HS) were collected and the PAB was measured. According to the normal value of PAB in HS, the patients were divided into two groups; patients with increased serum PAB and those with normal serum PAB values. In patients with increased PAB value, the correlation of PAB value with RA disease activity [(DAS28ESR)], biochemical parameters, and BMI were determined., Results: Significantly higher serum PAB values were found in the whole RA group of patients (88.69±39.42 HK) in comparison to HS (53.57±25.10 HK), p . 0.05. There was no significant correlation between PAB values and RA disease activity. In patients with elevated serum PAB value; serum cholesterol, triglycerides and BMI were significantly higher in comparison to patients with normal values., Conclusion: The PAB test can show the oxidative stress in RA patients. Further research should be done to determine the potency of the PAB assay as a tool for monitoring adverse effect of oxidative stress in RA, as well as the effect of antioxidant therapies in the outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The prevalence of abdominal obesity is on the rise worldwide. Previous studies have indicated the higher diagnostic value of body fat distribution pattern compared with general body in abdominal obesity assessments. Several non-pharmacological methods have been suggested for obesity management, of which acupuncture has gained a great deal of research interest with promising results. This study aimed to comparatively evaluate the effects of conventional auricular and body electroacupuncture on abdominal fat mass in obese men., Methods: The volunteers were randomly divided into four groups, including 2 interventions and 2 controls. This study was conducted on 80 obese volunteer men with Body Mass Index (BMI) range of 30-40 kg/m2.The intervention groups including real body electroacupuncture (A), real auricular acupuncture (C) and the control groups containing sham body electroacupuncture (B), and sham auricular acupuncture (D). All groups were in combination with a low-calorie diet for 6 weeks. BMI, Trunk Fat Mass (TFM), Waist Circumference (WC), and Hip Circumference (HC) were measured pre- and post-intervention., Results: In group A, respectively a significant reduction was shown in BMI (P < 0.005), TFM (P < 0.005), WC (P < 0.05, P < 0.005) and HC (P < 0.005) when compared with controls (Groups B and D). Interestingly, group C had significant decreases in BMI (P < 0.005), TFM (P < 0.01, P < 0.005), WC (P < 0.005) and HC (P < 0.001) after comparison with the sham. Likewise, WC (P < 0.05) and HC (P < 0.05) were significantly reduced post- intervention when compared with two treatment groups., Conclusions: In our study, acupuncture treatment (body or auricular) seemed to have an effect on reducing BMI, TFM, WC and HC. Comparison of the two types of treatment (body and auricular acupuncture) suggests that the two types of acupuncture had similar effects on reducing BMI and TFM, but body electroacupuncture is more effective in reducing WC and auricular in HC. It seems that both auricular and body electro-acupuncture combined with a low-calorie diet are efficient, simple and painless methods to reduce respectively the HC and WC fat in obese men, compared with conventional techniques., Trial Registration: IRCT201201127117N2.

Background: The cultured mesenchymal stem cells (MSC) have been used in many clinical trials; however, there are still some concerns about the cultural conditions. One concern is related to the use of FBS as a widely used xenogeneic supplement in the culture system. Human platelet-rich plasma (hPRP) is a candidate replacement for FBS. In this study, the effect of hPRP on MSC proliferation and osteogenic differentiation has been evaluated., Methods: Human adipose-derived stem cells (hADSC) were expanded. Cells from the third passage were characterized by flow cytometric analysis and used for in vitro experiments. Resazurin and alizarin red stains were used for cell proliferation and osteogenic differentiation assays, respectively., Results: Treatment with hPRP resulted in a statistically significant increase in cell proliferation compare to the negative control group (P<0.001). Cell proliferation in the 15% hPRP group was also significantly higher than that in the 10% hPRP group (P<0.05). Additionally, it caused less osteogenic differentiation of the hADSC compared to the FBS (P<0.001), but in comparison to negative control, it caused acceptable mineralization (P<0.001)., Conclusion: These findings indicate that hPRP not only improves the proliferation but also it can be a suitable substitution in osteogenic differentiation for clinical purposes. However, the clinical application value of hPRP still needs more investigation.

Background: The prevalence of obesity, a major public health problem, is increasing in many countries, including Iran. Leptin, a peptide hormone that is released from adipocytes, is a major factor in appetite regulation. Levels of plasma leptin increase with increased body fat mass (BFM). Research has found acupuncture to be effective both in weight loss and suppression of appetite. Although a few studies have reported the effect of body and ear acupuncture on leptin levels, researchers have performed few studies on the effect of body electroacupuncture in humans., Objective: The research team examined the effects of body electroacupuncture and a low-calorie diet on plasma leptin in obese and overweight individuals with an excess (phlegm-dampness or phlegm-heat) or deficiency (spleen/stomach qi deficiency or primary qi deficiency) pattern according to Chinese medicine., Design: The research team randomly assigned participants to one of two groups, intervention or control., Setting: This study occurred in the nutritional clinic at Ghaem Hospital in Mashhad, Iran., Participants: Participants were individuals (N = 86) between 18 and 65 years of age with body mass indexes (BMI) between 25 and 45 kg/m2., Intervention: The intervention group (n = 47) received actual electroacupuncture, and the control group (n = 47) received sham acupuncture. Both groups consumed a low-calorie diet for 6 weeks., Outcome Measures: The research team measured plasma leptin, BFM, body weight (BW), and BMI before and after treatment., Results: For participants in the intervention group with both the excess and the deficiency patterns, the research team found a significant reduction in plasma leptin (24.96%, P = .001) and BFM (8.29%, P = .001). In the control group, the team found a less significant reduction in leptin and BFM. The difference between the two groups was significant for leptin (P = .03) but not for BFM (P = .8)., Conclusions: While body electroacupuncture with a low-calorie diet can reduce plasma leptin concentration, the mechanism will require further clarification.

Objective(s): Crocin is the chemical ingredient primarily responsible for the color of saffron. It has different pharmacological effects such as antioxidant, anticancer and memory improving activities. Crocin tablets were evaluated for short-term safety and tolerability in healthy adult volunteers., Materials and Methods: The study was a randomized, double-blind, placebo-controlled design consisting of one month treatment of crocin tablets. Volunteers who fulfilled inclusion and exclusion criteria were randomized into 2 groups of 22 each (males and females) and received 20 mg crocin tablets or placebo. General measures of health were recorded during the study such as hematological, biochemical, hormonal and urinary parameters in pre and post-treatment periods., Results: No major adverse events were reported during the trial. Crocin tablets did not change the above parameters except that it decreased amylase, mixed white blood cells and PTT in healthy volunteers after one month., Conclusion: This clinical safety evaluation showed a relatively safe and normal profile for crocin in healthy volunteers at the given doses within the trial period.

Objective(s): This study was designed to evaluate the cardioprotective effect of Crocus sativus L. (saffron) aqueous extract and safranal, the major constituent of the essential oil of saffron, on lipid peroxidation, biochemical parameters and histopathological findings in isoproterenol (ISO)-induced myocardial infarction in Wistar rats., Materials and Methods: The saffron extract (20, 40, 80 and 160 mg/kg/day IP) or control were administered for 9 days along with ISO (85 mg/kg, SC, at 24 hr interval) on 8th and 9th day in rats. Activities of creatine kinase-muscle, brain (CK-MB) and lactate dehydrogenase (LDH) were measured using standard commercial kits. The level of malondialdehyde in heart tissue was estimated with thiobarbituric acid reactive species test. For histopathological examination, hematoxylin and eosin (H&E) staining was used., Results: ISO administration induced a statistically significant increase (P< 0.001) in serum LDH and CK-MB and a significant increase (P< 0.001) in the levels of thiobarbituric acid reactive substances (TBARs) in the heart as compared to vehicle control rats. Saffron pretreatment (20, 40, 80 and 160 mg/kg IP) or safranal pretreatment (0.025, 0.050, 0.075 ml/kg IP) for 8 days, significantly decreased (P< 0.001) the serum LDH and CK-MB and myocardial lipid peroxidation as compared to ISO- induced rats. Histological findings of the heart sections confirmed myocardial injury with ISO administration and preserved nearly normal tissue architecture with saffron or safranal pretreatment., Conclusion: Saffron and safranal may have cardioprotective effect in ISO-induced myocardial infarction through modulation of oxidative stress in such a way that they maintain the redox status of the cell.

Background: Human leptin is a peptide hormone that is released from white adipocytes. The absence of leptin or its receptor leads to uncontrolled food intake, leading to obesity. In the present work, the effects of auricular acupressure combined with low-calorie diet on the leptin hormone level were investigated., Methods: Volunteers (n=86) with body mass indices (BMI) between 25 and 45 kg/m² were randomised into a case (n=43) or a control (n=43) group. Participants in each group received a low-calorie diet for 6 weeks. The case group was treated with auricular acupressure and the control group received a sham procedure. Plasma leptin levels, body fat mass, body weight and BMI were measured before and after treatment., Results: Participants who received auricular acupressure showed significant reductions in their plasma leptin levels (18.57%, p<0.01) as well as in their body fat mass (4%, p<0.05). These changes were not observed in the control group. The reduction in leptin was significantly greater in the acupressure group than the controls., Conclusions: Auricular acupressure combined with a low-calorie diet significantly reduced plasma levels of leptin. However, the mechanism of this reduction is not clear.

Objective: The relationships between body fat distribution, lipid profile and blood pressure, have not been studied extensively in young population. This study was designed to evaluate the association between measures of adiposity and established cardiovascular risk factors in adolescent girls., Methods: A total of 477 adolescent girls aged 15 to 18 years were recruited from Mashhad high schools. Socio-demographic characteristics were assessed using a self-administered questionnaire. Anthropometric assessments, blood pressure measurement and biochemical assessment were performed. Total and regional fat mass were determined by bio-impedance analysis. Cardiovascular disease risk factors were assessed in relation to body fat measures with adjustment for confounder factors including age and family socioeconomic status., Findings: The prevalence of overweight and obesity was 14.6% and 3.4% respectively; 16% of study population had greater fat mass compared to its ideal distribution. The majority of cardiovascular risk factors, especially systolic and diastolic blood pressure, triglyceride concentration, CRP and fasting blood sugar were significantly higher in group with a high body fat when compared to those with normal and low values. All anthropometric indices showed significant correlation with fat mass, fat free mass, total and regional body fat percent (P<0.001). After adjustment for age and family socioeconomic status, a high fat mass especially, truncal fat, was positively associated with triglyceride and blood pressure., Conclusion: Adiposity, especially truncal adiposity, which can be assessed by simple measures such as Body Mass Index (BMI) and Waist Circumference (WC) may predispose adolescent girls for demonstration of metabolic abnormalities and consequently cardiovascular diseases.

Background Aims: Recalcitrant diabetic wounds are not responsive to the most common treatments. Bone marrow-derived stem cell transplantation is used for the healing of chronic lower extremity wounds., Methods: We report on the treatment of eight patients with aggressive, refractory diabetic wounds. The marrow-derived cells were injected/applied topically into the wound along with platelets, fibrin glue and bone marrow-impregnated collagen matrix., Results: Four weeks after treatment, the wound was completely closed in three patients and significantly reduced in the remaining five patients., Conclusions: Our study suggests that the combination of the components mentioned can be used safely in order to synergize the effect of chronic wound healing.

Background: Oxidative stress is thought to play an important role in the pathogenesis of stroke., Methods: In the present study, we assessed the extent of oxidative stress in the sera of 120 patients in the first 24 hours after the onset of stroke and 80 healthy control subjects using a novel assay of prooxidant-antioxidant balance (PAB) that can measure the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby giving a redox index., Results: In stroke patients median serum PAB values were significantly higher than that of the control group [125.50 (103.36 - 151.80) vs 43.40 (29.77 - 77.01), p < 0.001]. However, no significant difference was observed between subgroups of patients with transient ischemic attack (TIA), cerebral infarction or cerebral hemorrhage (p > 0.05). Median Serum PAB values were not significantly different in patients with different outcomes based on their 6-month prognosis (p > 0.05)., Conclusions: We conclude that serum PAB values are elevated in patients with stroke, indicating a heightened state of oxidative stress, but do not distinguish between stroke types or predict 6-month prognosis.

Introduction: We investigated the prevalence of type 2 diabetes mellitus and its relationship between gender, urbanisation, education, marital status and occupation in the Iranian population., Methods: A total of 3,778 men and women aged between 15 and 64 years were recruited by using a cluster-stratified sampling method from Khorasan province, northeast Iran. Using an interviewer-administrated questionnaire, demographical data including gender, urbanisation, education, marital status and occupation was collected. Anthropometrical and biochemical measurements were taken for each subject. Associations of type 2 diabetes mellitus and other variables were tested for significance., Results: The prevalence of diabetes mellitus (defined as fasting blood sugar equal to or more than 126 mg/dL) was 5.5 percent, and the prevalence in men and women was 5.1 percent and 5.8 percent, respectively, with a significantly higher prevalence among urban dwellers (seven percent) compared to that of the rural subgroup (three percent, p-value is less than 0.001). Diabetes mellitus was found to be most prevalent among the older age group (age more than 60 years, 10.9 percent), those who were retired (14.4 percent), and illiterate (6.1 percent, p-value is less than 0.001). Marital status was not significantly related to diabetes mellitus (p-value equals 0.09)., Conclusion: The prevalence of diabetes mellitus is related to some sociodemographical factors within the Iranian population. Thus the preventive strategies should be based on the affective factors. The urbanisation of the population with the migration of people from rural to urban areas may account in part for the increasing prevalence of type 2 diabetes mellitus in Iran.

Anti-melatonin monoclonal antibodies (MAb) were prepared following coupling melatonin to bovine serum albumin (BSA) by Mannich reaction. Balb/c mice were immunized via injection of the melatonin-BSA intraperitonally. The spleen cells producing high titer of antibody were fused with myeloma cells of SP2/0 origin. After two limiting dilutions, two stable clones (AS-H10 and AS-D26) exhibiting best properties were selected for further studies. The class and subclass of two MAbs were found to be IgG(1) and IgG(2a) with lambda and kappa light chains, respectively. Antibodies secreted by these two clones showed high affinity of about 10(9)M(1). Study of the specificity criteria showed that these clones had no cross reactivity with indolic, aromatic, and imidazole ring-containing compounds, and had high specificity towards melatonin. The calibration curve was constructed with a sensitivity range of 10 ng/mL to 10 microg/mL. In conclusion, these MAbs may be useful for immunoassay of melatonin.

Objectives: Determination of the prooxidant-antioxidant balance (PAB) in patients with angiographically defined coronary artery disease (CAD+) by a modified PAB assay and presentation of PAB value as a novel cardiovascular risk factor., Design and Methods: For 61 patients with CAD+ and 63 healthy volunteers, the PAB were measured and its correlation was determined with anthropological and clinical parameters., Results: A significant increase of the PAB value was observed in patients in comparison to control group. A correlation, which is not quite significant, was noted between angiographic finding (number of diseased vessel) and the PAB values in patients. A significant positive correlation was established between the PAB value and systolic blood pressure, diastolic blood pressure, smoking, fasting blood sugar and serum urea concentration; and a significant negative correlation was established between PAB value and serum creatinine and bilirubin., Conclusions: This study shows that the PAB value may be considered as a cardiovascular risk factor. Further clinical research is needed to substantiate the potency of the PAB value as a cardiovascular risk factor.

Introduction: We evaluated the ratio of free to total prostate-specific antigen (PSA) and PSA to protein concentrations in saliva and serum of healthy men., Materials and Methods: Concentrations of protein, free PSA, and total PSA in serum and saliva were measured in 30 healthy men aged 42 to 73 years, and their ratios were compared between the two fluids., Results: There was a significant direct correlation between serum free-total PSA ratios of serum and saliva (P = .04) and between total PSA-protein ratios of serum and saliva (P = .02). Also, there were significant correlations between total and free PSA levels in saliva (P = .05) and between those in serum (P < .001). Significant inverse and direct correlations were detected between the body mass index and serum values of total PSA-protein (P = .04) and free-total PSA (P = .01), respectively., Conclusion: We can use saliva sample instead of serum sample for estimation of free-total PSA and total PSA-protein levels in men without prostate diseases. There is, however, a pressing need for much additional research in this area before the true clinical value of saliva as a diagnostic fluid can be determined.

Background: An imbalance between zinc and copper metabolism has been reported to predispose to coronary artery disease (CAD) in Western populations, but there are little data for other racial groups. We have therefore investigated the association between serum copper and zinc, and CAD in Iranian subjects undergoing coronary angiography., Methods: Serum copper, zinc, fasting lipid profile, and blood glucose levels were measured in 114 patients (67 male and 47 female) undergoing routine coronary angiogram. Anthropometric features including blood pressure were determined using standard procedures. Demographic characteristics, including menopausal status and smoking habit, were assessed by questionnaire., Results: Male patients had lower serum copper (p<0.05), lower serum zinc (p<0.05), and higher serum zinc/copper ratio (p<0.05) than females. Serum copper and zinc concentrations were significantly lower in the subjects with angiographically defined CAD than those patients with a normal angiogram, although the zinc/copper ratio was higher in these patients (p<0.001). Serum copper (r=-0.303, p<0.001) and zinc (r=-0.250, p<0.01) concentrations were both inversely related to age, and copper was positively associated with fasting serum triglycerides (r=0.188, p<0.05)., Conclusion: Serum copper and zinc concentrations were significantly lower in Iranian patients with abnormal versus those with a normal angiogram. However, the zinc/copper ratio was higher in patients with CAD compared to subjects without CAD. Serum zinc and copper concentrations appear to be influenced by several physiological factors including age and gender.