Silibinin effects on cognitive disorders: Hope or treatment?

Objective: Almost all diseases of the nervous system are related to neuroinflammation, oxidative stress, neuronal death, glia activation, and increased pro-inflammatory cytokines. Cognitive disorders are one of the common complications of nervous system diseases. The role of some plant compounds in reducing or preventing cognitive disorders has been determined. Silibinin is a plant bioflavonoid and exhibits various effects on cognitive functions. This article discusses the different mechanisms of the effect of silibinin on cognitive disorders in experimental studies. Materials and Methods: Databases, including ISI, , Google Scholar, Scopus, Medline and PubMed, were investigated from 2000 to 2021, using related keywords to find required articles. Results: Silibinin can improve cognitive disorders by different pathways such as reducing neuroinflammation and oxidative stress, activation of reactive oxygen species- Brain-derived neurotrophic factor- Tropomyosin receptor kinase B (ROS-BDNF-TrkB) pathway in the hippocampus, an increase of dendritic spines in the brain, inhibition of hyperphosphorylation of tau protein and increasing the expression of insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R), inhibiting inflammatory responses and oxidative stress in the hippocampus and amygdala, and decrease of Homovanillic acid/Dopamine (HVA/DA) ratio and 3,4-Dihydroxyphenylacetic acid + Homovanillic acid/Dopamine (DOPAC+ HVA/DA) ratio in the prefrontal cortex and 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratio in the hippocampus. Conclusion: These results suggest that silibinin can be considered a therapeutic agent for the symptom reduction of cognitive disorders, and it acts by affecting various mechanisms such as inflammation, programmed cell death, and oxidative stress.

Artemisia Absinthium Extract Attenuates the Quinolinic Acid-Induced Cell Injury in OLN-93 Cells.

OBJECTIVE: Increased quinolinic acid (QA) accumulation has been found in many neurodegenerative diseases. Artemisia absinthium (A. absinthium) has been reported to have neuroprotective and antioxidant activities. This study was designed to evaluate the effect of A. absinthium in QAinduced neurotoxicity in OLN-93 Cells. METHODS: OLN-93 cells were cultured in a DMEM medium containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and 100 µg/ml streptomycin. The cells were pretreated with concentrations of A. absinthium extract for two h and then exposed to QA for 24 h. After 24 h cell viability, the level of malondialdehyde (MDA), reactive oxygen species (ROS), and apoptotic cells were quantitated in OLN-93 Cells. RESULTS: Pretreatment with A. absinthium extract prevented the loss of cell viability in OLN-93 cells. ROS generation, lipid peroxidation, and apoptosis in QA-injured OLN-93 cells were reduced following A. absinthium extract pretreatment. CONCLUSION: A. absinthium extract exerts its neuroprotective effect against QA-induced neurotoxicity via oxidative stress and apoptosis modulation.

Susceptibility of domestic and companion animals to SARS-CoV-2: a comprehensive review.

The ongoing coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a large global outbreak. The reports of domestic animals' infection with SARS-CoV-2 raise concerns about the virus's longer-lasting spread, the establishment of a new host reservoir, or even the evolution of a new virus, as seen with COVID-19. In this review, we focus on the susceptibility of domestic animals, especially companion animals, towards SARS-CoV-2 in light of existing studies of natural infection, experimental infection, and serological surveys. Susceptibility of domestic and companion animals to SARS-CoV-2 infection.

Synergistic effect of ellagic acid and gabapentin in a rat model of neuropathic pain.

BACKGROUND: Neuropathic pain is a subtype of chronic pain characterized by a primary lesion or dysfunction of the peripheral or central nervous system. The current pain management of neuropathic pain is inadequate and needs new medications. AIM: We studied the effects of 14 days of intraperitoneal ellagic acid (EA) and gabapentin administration in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the right sciatic nerve. METHODS: Rats were divided into six groups: (1) control, (2) CCI, (3) CCI + EA (50 mg/kg), 4) CCI + EA (100 mg/kg), 5) CCI + gabapentin (100 mg/kg), and 6) CCI + EA (100 mg/kg) + gabapentin (100 mg/kg). Behavioral tests, including mechanical allodynia, cold allodynia, and thermal hyperalgesia, were conducted on days - 1(pre-operation), 7, and 14 post-CCI. In addition, at day 14 post-CCI, spinal cord segments were collected to measure the expression of inflammatory markers, including tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and oxidative stress markers, including malondialdehyde (MDA) and thiol. RESULTS: CCI increased mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats which were reduced by treatment with EA (50 or 100 mg/kg), gabapentin, or their combination. CCI increased TNF-α, NO, and MDA levels and decreased thiol content in the spinal cord, which all were reverted by administration of EA (50 or 100 mg/kg), gabapentin, or their combination. CONCLUSION: This is the first report on ellagic acid's ameliorative effect in rats' CCI-induced neuropathic pain. This effect can be attributed to its anti-oxidative and anti-inflammatory, thus making it potentially useful as an adjuvant to conventional treatment.

Cerium Oxide Nanoparticles Ameliorate Oxidative Stress, Inflammation, and Pain Behavior in Neuropathic Rats.

BACKGROUND: Neuropathic pain originating from a dysfunction in the nervous system is often intractable and chronic. Recently, several studies using nanoparticles suggested a new way to control neuropathic pain. This study intended to explore the potential neuroprotective effect of Cerium Oxide Nanoparticles (CNPs) synthesized by pullulan in neuropathic pain in rats. METHODS: On the right common sciatic nerve of male Wistar rats, the chronic constriction injury (CCI) procedure was used to establish a neuropathic pain model. CNPs were injected into the caudal vein of the rat. Behavioral methods were used to detect mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats. Besides, inflammation factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, nitric oxide (NO), and markers of oxidative stress, including Malondialdehyde (MDA) and total thiol, were measured in the spinal cord segment of rats. RESULTS: In rats with CCI, mechanical allodynia, cold allodynia, and thermal hyperalgesia developed, which improved when the rats were administered CNPs. Spinal cord specimens of CCI rats had elevated inflammation and oxidative stress status (↑IL-1ß, ↑TNF-α, ↑NO, ↑MDA) and decreased antioxidative levels (↓total thiol). As a result of CNPs treatment, these changes were reversed in the spinal cord specimens. CONCLUSION: CNPs alleviate neuropathic pain by exhibiting antioxidative and anti-inflammatory activities.

Evaluation of Antiarthritic and Antinociceptive Effects of Cedrol in a Rat Model of Arthritis.

Pharmacological studies revealed that cedrol, a natural sesquiterpene, has antioxidant, anti-inflammatory, and analgesic properties. This study is aimed at evaluating the potential antiarthritic activity of cedrol in a rat experimental model of arthritis induced by using complete Freund's adjuvant (CFA). Arthritis was induced in Wistar rats by CFA (0.1 ml) injection. Cedrol (10 and 20 mg/kg) and indomethacin (5 mg/kg) were orally administered from day one and continued for 21 days. The antiarthritic activity was assessed through mechanical allodynia and thermal hyperalgesia responses, paw edema assessment, and arthritis scores. Serum TNF-α and IL-1ß levels were measured for the evaluation of inflammation. Furthermore, serum oxidative stress markers, including malondialdehyde (MDA) and thiol levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were also assessed. Oral administration of cedrol and indomethacin significantly decreased paw edema and arthritis score. Besides, cedrol and indomethacin significantly decreased pain responses. In the serum of the CFA group, TNF-α, IL-1ß, and MDA were higher, while thiol and SOD and GPx were lower than the control group. Treatment by cedrol and indomethacin corrected the biochemical parameters in the serum. In this study, cedrol offers potential antiarthritic properties through its anti-inflammatory and antioxidant effects.

The Potential Role of Green Tea and its Main Constituent (Epigallocatechin -3-Gallate) in Pain Relief: A Mechanistic Review.

Medicinal plants and dietary supplements may provide an effective and safe treatment for pain relief. Green tea is one of the most common beverages with many several pharmacological activities. The results of various studies have indicated that green tea possesses antinociceptive effects. Many of the protective effects of green tea in terms of pain relief are attributed to its antioxidant and anti-inflammatory properties. Epigallocatechin -3-gallate (EGCG), as one of the major phytochemical components in green tea, is effective in the management of pain through suppression of inflammation and oxidative stress. We have reviewed the effects of green tea on pain and also discussed mechanisms involved in pain relief. This review suggests that green tea can be a safe and often effective treatment for pain.

The role of resveratrol as a natural modulator in glia activation in experimental models of stroke.

OBJECTIVE: Stroke is one of the most important causes of death and disability in modern and developing societies. In a stroke, both the glial cells and neurons develop apoptosis due to decreased cellular access to glucose and oxygen. Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene) as a herbal compound shows neuroprotective and glioprotective effects. This article reviews how resveratrol can alleviate symptoms after stroke to help neurons to survive by modulating some signaling pathways in glia. MATERIALS AND METHODS: Various databases such as ISI Web of Knowledge, Scopus, Medline, PubMed, and Google Scholar, were searched from 2000 to February 2020 to gather the required articles using appropriate keywords. RESULTS: Resveratrol enhances anti-inflammatory and decreases inflammatory cytokines by affecting the signaling pathways in microglia such as AMP-activated protein kinase (5' adenosine monophosphate-activated protein kinase, AMPK), SIRT1 (sirtuin 1) and SOCS1 (suppressor of cytokine signaling 1). Furthermore, through miR-155 overexpressing in microglia, resveratrol promotes M2 phenotype polarization. Resveratrol also increases AMPK and inhibits GSK-3ß (glycogen synthase kinase 3 beta) activity in astrocytes, which release energy, makes ATP available to neurons and reduces reactive oxygen species (ROS). Besides, resveratrol increases oligodendrocyte survival, which can lead to maintaining post-stroke brain homeostasis. CONCLUSION: These results suggest that resveratrol can be considered a novel therapeutic agent for the reduction of stroke symptoms that can not only affect neuronal function but also play an important role in reducing neurotoxicity by altering glial activity and signaling.

Insulin-Like Growth Factor 2 (IGF-2) Regulates Neuronal Density and IGF-2 Distribution Following Hippocampal Intracerebral Hemorrhage.

BACKGROUND: The insulin-like growth factor 2 (IGF-2) is a growth factor and anti-inflammatory cytokine that plays a crucial role in memory consolidation. However, the precise role of this factor in acute brain damage is still unclear. The present study aimed to evaluate the variations in hippocampal IGF-2 distribution on different days and investigate the effect of recombinant IGF-2 on memory cell density, and IGF-2 distribution following acute hippocampal damage resulting from intracerebral hemorrhage (ICH). METHODS: ICH was induced by injection of 100 µL of autologous blood into the left hippocampus of 72 male Sprague-Dawley rats. Recombinant IGF-2 was injected into the damaged hippocampus 30 min post-induction of ICH in the ICH-IGF-2 group. Then, on postoperative days 1, 3, 7, and 14, samples of brain tissue were collected to perform histopathological and immunohistochemical examinations. RESULTS: The stereological study indicated that the volume of the hippocampus and the number of neurons had a significant reduction, and the infarct volume had a significant increase following ICH. Following the injection of IGF-2, a significant improvement was observed in stereological studies. Immunohistochemical data showed that IGF-2 distribution increased in the hippocampus on different days after ICH, and IGF-2 injection led to a dramatic reduction in this distribution. CONCLUSIONS: In summary, the gradual increase of endogenous IGF-2 as growth and anti-inflammatory factor following hemorrhagic stroke reveals a critical role of this factor in brain recovery after injury. Moreover, the injection of IGF-2 can prevent cell death and alleviate the damage caused by the hemorrhagic stroke.

The effects of acetyl-11-keto-ß-boswellic acid on brain cytokines and memory impairment induced by lipopolysaccharide in rats.

The therapeutic effects of the olibanum, the resin of Boswellia serrata on inflammatory diseases have been reported. There are more than 200 active ingredients in this resin including acetyl-11-keto-ß-boswellic acid (AKBA). We proposed that AKBA can improve memory impairment induced by cerebral inflammation following the administration of lipopolysaccharide (LPS). Forty male rats were grouped and received the following treatments: Control (diluted DMSO + saline), LPS (diluted DMSO + 1 mg/kg LPS), LPS- AKBA 5 and LPS- AKBA 10 (5 or 10 mg/ kg AKBA before LPS). Morris water maze (MWM), passive avoidance (PA) and biochemical tests were carried out. Pre-treatment with both doses of AKBA improved memory performance in MWM and PA tests (P < 0.05 to P < 0.001). Pre-treatment by AKBA improved the levels of hippocampal IL-10 (P < 0.001), BDNF (P < 0.001), CAT (P < 0.05 and P < 0.001), SOD P < 0.001 and thiols (P < 0.01 and P < 0.001) while reduced IL-6 (P < 0.001), TNF-α (P < 0.001), NO (P < 0.05 and P < 0.001), GFAP (P < 0.001) and MDA (P < 0.001) levels. AKBA effectively ameliorated LPS-induced learning and memory impairments and improved BDNF in a neuroinflammation animal model. The effects seem to be due to setting a positive balance between pro-inflammatory to inflammatory cytokines and reinvigorate the antioxidant system.

Tanacetum parthenium enhances pentobarbital-induced sleeping behaviors.

OBJECTIVE: Sleep disorders are among the most common psychiatric and medical conditions. In the present study, the hypnotic effect of Tanacetum parthenium was studied in mice. MATERIALS AND METHODS: The hydro-alcoholic extract (HAE) of T. parthenium and three fractions of it, namely water fraction (WF), ethyl acetate fraction (EAF), and n-hexane fraction (NHF), were intraperitoneally (ip) administrated to mice 30 min before injection of sodium pentobarbital (30 mg/kg, ip). Then, 30 min after administration of HAE, motor coordination (rota-rod test) was evaluated. Besides, LD50 of HAE was determined and the cytotoxicity of HAE was evaluated in PC12 cells using the MTT assay. RESULTS: HAE 50-200 mg/kg increased the sleeping time. EAF was the only fraction which could prolong the sleep duration and decrease sleep latency. The LD50 value was 4.8 g/kg. The extract induced no cytotoxic effects in PC12 cell line. CONCLUSION: The results suggested that T. parthenium potentiates pentobarbital hypnosis without causing toxic effects. Probably, its effects are mediated by the components present in EAF of this plant.

The effect of ultrasound cavitation in combination with cryolipolysis as a non-invasive selective procedure for abdominal fat reduction.

BACKGROUND AND AIM: Fat reduction and body contouring have become popular procedures in the cosmetic surgery industry over the past decade. There have been studies to replace invasive methods such as liposuction, with safer non-invasive procedures. We aimed to evaluate the effect of a non-invasive combination therapy of ultrasound cavitation and cryolipolysis on abdominal adipose tissue. METHODS: This pilot interventional study comprised 90 female individuals aged 18-65-years-old who were recruited into one of three groups of 30 participants. Group 1 was treated with diet alone (the control group), group 2 with cryolipolysis and diet, and group 3 with a combination of ultrasound cavitation, cryolipolysis, and diet for 8 weeks. Anthropometric parameters were measured before, during, and after the trial included total body weight, body mass index(BMI), body fat mass, fat-free mass, and abdomen circumference. RESULTS: All three groups demonstrated significant reductions in each parameter at the end of the intervention (P < 0.01). Apart from fat-free mass (P = 0.66), the combination therapy significantly reduced body fat mass, weight, BMI, and abdomen circumference compared to the control group (P < 0.01). There was no significant difference between the combination therapy and cryolipolysis-alone groups. CONCLUSION: Treatment using a combination of cryolipolysis and ultrasound cavitation is no more effective in improving the anthropometric indices than cryolipolysis alone.

Bufo viridis secretions improve anxiety and depression-like behavior following intracerebroventricular injection of amyloid ß.

BACKGROUND AND PURPOSE: Venenum Bufonis is a Chinese traditional medicine produced from the glandular secretions of toads that contain biogenic amines, which have anti-inflammatory properties. The present study aimed to examine the effect of Bufo viridis secretions (BVS) on anxiety and depression-like behavior and hippocampal senile plaques volume in an animal model of Alzheimer's disease (AD). EXPERIMENTAL APPROACH: Thirty-eight male Wistar rats were used. AD was induced by amyloid-beta (Aß1-42) (10 µg/2 µL, intracerebroventricular injection, icv) and then BVS at 20, 40, and 80 mg/kg were injected intraperitoneally (ip) in six equal intervals over 21 days. Anxiety and depression-like behavior were assessed using behavioral tests including open field test (OFT), elevated plus maze (EPM), and forced swimming test (FST) 21 days after the surgery. The volume of senile plaques was assessed based on the Cavalieri principle. FINDINGS/RESULTS: Results of the OFT showed that the central crossing number and the time in the AD group were significantly decreased compared to the sham group (P < 0.01 and P < 0.001, respectively). Also, the values of these two parameters significantly increased in the AD + BVS80 group than the AD group (P < 0.05 and P < 0.001, respectively). The time spent in the closed arm in the EPM dramatically increased in the AD group compared to the sham group (P < 0.05) and significantly decreased in the AD + BVS80 group compared to the AD group (P < 0.05). Results of the FST indicated that immobility time had a reduction in the AD + BVS20 (P < 0.01), AD + BVS40, and AD + BVS80 groups compared to the AD group (P < 0.001). The volume of senile plaques in the hippocampus showed a reduction in the treatment groups in comparison with the AD group (P < 0.001 for all). CONCLUSION AND IMPLICATIONS: Results revealed that BVS injection could improve symptoms of anxiety and depression and decrease senile plaques in the hippocampus in an animal model of AD.

Fibroblast Growth Factor 1 Gene-Transfected Adipose-Derived Mesenchymal Stem Cells Modulate Apoptosis And Inflammation In The Chronic Constriction Injury Model of Neuropathic Pain.

Stem cell therapy is noted for its clinical effect in the treatment of neuropathic pain. This study aimed to investigate the potential anti-apoptotic and anti-inflammatory effects of adipose-derived mesenchymal stem cells (AD-MSCs) and fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells (AD-MSCs FGF1) on chronic constriction injury (CCI) of the rat's sciatic nerve. The rats that underwent CCI were treated with AD-MSCs and AD-MSCs FGF1. Bax, Bcl2, and caspases 3, the major contributors of apoptosis, and inflammatory markers including Iba-1, IL1-ß, and MMP-2 were evaluated in the lumbar portion (L4-L6) of the spinal cord through western bloating at days 3 and 14. The ratio of Bax/Bcl2, cleaved caspases 3, MMP-2, IL-1ß, and Iba1, was elevated in CCI animals compared to sham-operated animals and decreased following treatment with both AD-MSCs and AD-MSCs FGF1. However, the effect of AD-MSCs FGF1 was significantly higher than AD-MSCs. These data suggest that the administration of AD-MSCs FGF1 through modulating apoptosis and neuroinflammation could be considered a promising medicine for treating neuropathic pain.

VEGF gene polymorphism interactions with dietary trace elements intake in determining the risk of metabolic syndrome.

There is a complex association among genetic, metabolic, and environmental factors in determining the risk of metabolic syndrome (MetS). The aim of this study was to investigate the role of the association between the dietary intake of iron, copper, zinc, manganese, selenium, and iodine (assessed by 24 recall) with vascular endothelial growth factor variants (rs6921438, rs4416670, rs6993770, and rs10738760), on the risk of MetS. Two-hundred and forty-eight individuals with MetS and 100 individuals without MetS were recruited. The dietary intake and the daily average of energy and nutrient intake were obtained by a questionnaire and quantified using Diet Plan 6 software. DNA was extracted from EDTA anticoagulated whole blood. The SNPs were assessed using using a Sequenom iPLEX Gold assay. Data analysis was undertaken using the Student t test, χ2 test and logistic regression using SPSS 11.5 software. There was a significant association between low dietary iron intake and rs6993770 (ß = .10, P < .05), and a low dietary zinc and a high manganese intake with rs6921438 in relation to the presence of MetS (ß = -.17, P < .05, ß = -.30, P < .05, respectively). Our data showed the association of rs6993770 with iron intake and rs6921438 with zinc and manganese intake, indicating further investigation in a larger population to evaluate their values.

Fibroblast Growth Factor Type 1 (FGF1)-Overexpressed Adipose-Derived Mesenchaymal Stem Cells (AD-MSCFGF1) Induce Neuroprotection and Functional Recovery in a Rat Stroke Model.

Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSCFGF1) on transient experimental ischemic stroke in rats. Stroke induction was made by transient middle cerebral artery occlusion (tMCAO). 2 × 106 AD-MSCFGF1 was administrated intravenously 30 min after carotid reperfusion. The ability of technetium99m-hexamethyl propylene amine oxime (99mTc-HMPAO)-labeled AD-MSCFGF1 to enter into ischemic brain was evaluated 2 h post injection. 24 h post operation, the neurological recovery (rotarod and Roger's tests), the infarct volume (2, 3, 5-triphenyltetrazolium chloride, TTC assay), apoptosis rate (TUNEL assay), and the expression of FGF1 protein (western blotting) in the ischemic hemisphere were assessed. The 99mTc-HMPAO-labeled AD-MSCFGF1 could enter into the ischemic brain. Ischemic hemisphere activity was significantly higher than that observed in the contralateral hemisphere (p = 0.002). The administration of AD-MSCFGF1 resulted in significant improvement of neurological function tests and increased density of FGF1 protein in the peri-infarct area, while the infarct volume and the apoptotic index were significantly decreased, in comparison to the other treated groups. In conclusion, acute intravenous administration of AD-MSCFGF1 can be a novel and promising candidate approach for the treatment of ischemic stroke.

Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation.

The aim of this study was to investigate, for the first time, the effects of using adipose-derived mesenchymal stem cells (AD-MSCs) transfected with an episomal plasmid encoding fibroblast growth factor 1 (FGF1) (AD-MSCsFGF1), in providing the microenvironment required for angiogenic proliferation. The isolated rat AD-MSCs were positive for mesenchymal (CD29 and CD90) and negative for hematopoietic (CD34 and CD45) surface markers. Adipogenic and osteogenic differentiation of the AD-MSCs also occurred in the proper culture media. The presence of FGF1 in the conditioned medium from the AD-MSCsFGF1 was confirmed by Western blotting. G418 and PCR were used for selection of transfected cells and confirmation of the presence of FGF1 mRNA, respectively. Treatment with the AD-MSCFGF1-conditioned medium significantly increased the NIH-3T3 cell proliferation and human umbilical vein endothelial cell (HUVEC) tube formation compared to conditioned medium from nontransfected AD-MSCs (p < 0.001). In conclusion, the AD-MSCsFGF1 efficiently secreted functional FGF1, which promoted angiogenic proliferation. Using AD-MSCsFGF1 may provide a useful strategy in cell therapy, which can merge the beneficial effects of stem cells with the positive biological effects of FGF1 in various disorders, especially tissue defects, neurodegenerative, cardiovascular and diabetes endocrine pathologies, which remain to be tested in preclinical and clinical studies.

Relationship between serum cytokines receptors and matrix metalloproteinase 9 levels and coronary artery disease.

BACKGROUND: The prevalence of coronary artery disease (CAD) is increasing globally, supporting the need for the identification of novel biomarkers. Therefore in the present study, we have explored the association of SIL2A, SIL6R, STNFRI, STNFRII, and MMP9 in CAD patients. METHODS: Twenty one patients with angiographically defined CAD with more than 50% occlusion, at least, in one coronary artery and twenty healthy subjects (n=20) without the history of cardiovascular symptoms were enrolled. Demographic and biochemical analysis (e.g. Total Cholesterol (TC), Triglyceride (TG), and HDL-C) were measured in all the subjects. The level of cytokines receptor (SIL2A, SIL6R, SIL6R, STNFRI, STNFRII, and matrix metallopeptidase 9 (MMP9) were evaluated. RESULTS: Our results showed the higher level of MMP9 in patients group compared to the control subjects, while no significant differences were detected for other cytokines. In particular the level of MMP9 was significantly (P=.015) increased from 181.16 ng/mL (95%CI: 112.1-199.2) to 192.0 ng/mL (95%CI: 181.5-265.2). Moreover, the sensitivity and specificity of MMP9 were 95.45% and 45%, respectively, as detected by receiver operating characteristic (ROC) curves. CONCLUSION: We demonstrate the significant correlation of MMP-9 with CAD with sensitivity of 95.45%, suggesting its role as a biomarker in CAD patients. Further studies in larger population - preferably multicenter setting - are warranted to explore the functional role of this marker in coronary artery disease.

Effects of Streptozotocin-Induced Diabetes on Proliferation and Differentiation Abilities of Mesenchymal Stem Cells Derived from Subcutaneous and Visceral Adipose Tissues.

Introduction: Accumulated evidence indicates that there are intrinsic differences between adipose tissue-derived stem cells (ASCs) obtained from different body fat depots. Here, we compared the proliferation and multipotency of subcutaneous ASCs (SC-ASCs) and epididymal ASCs (ED-ASCs) before and after induction of diabetes by streptozotocin. Methods: The adipogenic and osteogenic abilities of rat SC-ASCs and ED-ASCs were evaluated using Oil Red O and Alizarin Red staining, respectively. The expression of adipocyte (PPAR-γ, LPL) and osteoblast (ALP, SPP1) specific mRNAs was evaluated by quantitative real-time PCR. MTT test was used for determination of cell proliferation capacity. Results: The proliferation of SC-ASCs was higher than ED-ASCs, both before and after diabetes induction (P<0.05). Diabetes increased the proliferative capability of SC-ASCs (P<0.05) but not ED-ASCs. Before diabetes, both adipogenic and osteogenic differentiation of SC-ASCs were higher than ED-ASCs (P<0.05). After diabetes, both SC-ASCs and ED-ASCs were able to differentiate into adipocyte and osteoblast, but the levels of differentiation were higher in SC-ASCs than in ED-ASCs (P<0.05). Diabetes decreased the expression of PPAR-γ and LPL, but increased the SPP1 and ALP expression in both SC-ASCs and ED-ASCs. Conclusion: Our data suggested that diabetes increases the proliferation of ASCs but decreases their adipogenic differentiation. Also, SC-ASCs have higher proliferation and differentiation abilities than ED-ASCs in normal and diabetic conditions so can be more preferable for cell therapy.

Association of Serum hs-CRP Levels With the Presence of Obesity, Diabetes Mellitus, and Other Cardiovascular Risk Factors.

BACKGROUND: Diabetes mellitus remains one of the major health problems of the 21st century and is associated with comorbidities including obesity and metabolic abnormalities. The study was conducted to evaluate serum high-sensitivity C-reactive protein (hs-CRP) levels, as a marker of inflammation, in a large sample of Iranian population without a history of cardiovascular or inflammatory disease and cancer, and to relate this to fasting blood glucose (FBG) and the presence of diabetes mellitus. METHODS: The study consisted of 7,762 subjects divided into four groups-nonobese/nondiabetic, obese/nondiabetic, nonobese/diabetic and obese/diabetic-based on the BMI classification and their FBG. Anthropometric characteristics were measured and blood was collected for the evaluation of fasted lipid profile, FBG and serum hs-CRP levels. RESULTS: Several clinical and biochemical characteristics were significantly different among the four groups: FBG, P < 0.001; total cholesterol (TC), P < 0.001; and triglyceride (TG), P < 0.001. The subjects with a serum hs-CRP >3 mg/dl had higher TC (P < 0.001), low-density lipoprotein cholesterol (LDL-C, P < 0.001), TG (P < 0.001), fat percentage (P < 0.001), and systolic and diastolic blood pressure (P < 0.001) compared with subjects with a serum hs-CRP <3 mg/dl. Multivariate analysis showed FBG, LDL-C, and waist circumference (WC) associated with increased serum hs-CRP levels (P < 0.001). CONCLUSIONS: FBG, LDL-C, WC and gender are independently associated with serum hs-CRP concentrations.