Plastic particle impacts on the cardiovascular system and angiogenesis potential.

The extensive application of plastics in different sectors such as packaging, building, textiles, consumer products, and several industries has increased in recent years. Emerging data have confirmed that plastic wastes and segregates are problematic issues in aquatic and terrestrial ecosystems. The decomposition of plastic particles (PPs) leads to the release of microplastics (MPs) and nanoplastics (NPs) into the surrounding environment and entry of these particles will be problematic in unicellular and multicellular creatures. It was suggested that PPs can easily cross all biological barriers and reach different organs, especially the cardiovascular system, with the potential to modulate several molecular pathways. It is postulated that the direct interaction of PPs with cellular and subcellular components induces genotoxicity and cytotoxicity within the cardiovascular system. Meanwhile, being inert carriers, PPs can intensify the toxicity of other contaminants inside the cardiovascular system. Here, in this review article, several underlying mechanisms related to PP toxicity in the cardiovascular system were discussed in detail.

Kynurenine and Beta-Alanine Serum Levels are Associated with the Expression of Wnt Pathway Genes in Patients with Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Despite its worldwide prevalence, there is currently no clear explanation for the mechanism of this disease. In addition, the lack of reliable and accurate biomarkers makes the early detection of PD difficult. Therefore, we examined serum beta-alanine and kynurenine levels and expression of Wnt pathway genes in leukocytes from patients with PD. METHODS: Ninety patients, 45 with PD and 45 healthy subjects, were enrolled in this study. Ten milliliters of blood were drawn from all participants. Serum levels of beta-alanine and kynurenine were measured by ELISA, and the expression of Wnt pathway genes in leukocytes was determined by real-time PCR. RESULTS: Serum levels of kynurenine and beta-alanine were higher in PD patients than in the control group. Data analysis also showed that the expression of some Wnt pathway genes was decreased in leukocytes. CONCLUSIONS: The correlation between serum levels of beta-alanine and kynurenine and the expression of the gene that encodes the Wnt signaling pathway in leukocytes was found in patients with PD. As a result, these biomarkers can be utilized for the early detection, monitoring, and treatment of patients with PD.

Investigation of serum levels of orexin-A, transforming growth factor ß, and leptin in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease affecting various inflammatory and nutritional parameters. Therefore, this study aimed to investigate the relationship between the Body Mass Index (BMI) of MS patients and the serum levels of leptin, orexin-A, and Transforming Growth Factor ß (TGF-ß). METHODS: This cross-sectional study included 25 patients suffering from MS and 40 healthy individuals as the case and control groups, respectively. The serum levels of leptin, orexin-A, and TGF-ß were assessed in the participants using the Enzyme-Linked Immunosorbent Assay methods. Moreover, data were analyzed using the descriptive statistical indices, t-test, chi-square test, and linear regression test. RESULTS: According to our results, the participants' mean age was 38.04 ± 7.53 and 40.23 ± 5.88 in the case and control groups, respectively. Also, the groups were not significantly different in gender, age, alcohol consumption, and smoking (p > 0.05). It was found that the mean serum levels of orexin-A and TGF-ß were significantly lower in the MS patients compared to the control group, while the mean serum leptin levels were significantly higher (42.8 vs. 18.9 ng/ml, p < 0.001). Moreover, there was no significant relationship between the BMI of the MS patients and their serum levels of orexin-A, TGF-ß, and leptin (p > 0.05). CONCLUSIONS: In conclusion, we found significantly lower levels of orexin-A and TGF-ß and a significantly higher level of leptin in the MS patients compared to the control group. In addition, there was no significant relationship between the BMI and the serum levels of orexin-A, TGF-ß, and leptin in MS patients.

Evaluation of the serum levels of Mannose binding lectin-2, tenascin-C, and total antioxidant capacity in patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) develops as a result of atherosclerosis. Atherosclerosis is a condition that leads to clogged arteries and can be caused by a variety of factors. Several studies have shown that various factors contribute to the development and progression of CAD. The aim of this study was to investigate the serum levels of MBL-2, TNC and TAC in patients with CAD and the relationship between these biochemical parameters and the progression of CAD. METHODS: In this study, 60 serum samples were obtained from CAD patients as the case group and 20 healthy serum samples as the control group. Serum levels of MBL-2 and TNC were measured by the ELISA method. Serum TAC level was determined by calorimetry (spectrophotometry). In addition, MDA serum level was measured by reaction with thiobarbituric acid (TBA). RESULTS: The mean age in the case and control groups was 58.4 ± 9.5 years and 85 ± 9.8 years, respectively. There was no significant difference in age, sex and family history in patients with CAD (p > 0.05), but there was a significant difference in blood pressure and smoking history (p > 0.05). Serum cholesterol, triglyceride, and LDL levels were significantly increased in the case group compared to the control group, while serum HDL-C levels were significantly decreased in the case group. Serum levels of MBL-2, TNC, and MDA were significantly increased in the case group compared to the control group. The serum level of TAC was significantly lower in the case group than in the control group. CONCLUSION: This study suggests that it is possible to diagnose patients with coronary artery disease (CAD) in the early stages of their disease and take preventive measures by measuring these parameters in serum. However, more research is needed before these serum parameters can be considered diagnostic biomarkers or therapeutic targets.

Docosahexaenoic acid attenuates the detrimental effect of palmitic acid on human endothelial cells by modulating genes from the atherosclerosis signaling pathway.

The formation of atherosclerotic changes leads to dysfunction in numerous cell types, especially endothelial cells. In the current experiment, we aimed to show the therapeutic effect of Docosahexaenoic acid on palmitic-induced atherosclerotic changes in the human endothelial lineage. Human Umbilical Vein Endothelial cells were incubated with 1 mM palmitic acid for 48 hours and then exposed to 40 µM docosahexaenoic acid for next 24 hours. Cellular atherosclerosis and lipid removal were confirmed by the application of Oil red O solution. The cell survival rate was studied by using MTT assay and flow cytometry analysis of Annexin V. We also measured the protein level of tumor necrosis factor-α and granulocyte-macrophage colony-stimulating factor by immunofluorescence imaging. The transcription level of genes participating in the atherosclerosis signaling pathway was monitored in atherosclerotic endothelial cells before and after treatment with docosahexaenoic acid. The viability of the cells was reduced after 48 hours incubation with palmitic acid. It is noteworthy that the number of viable endothelial cells was increased after exposure to docosahexaenoic acid. Compared with the cells that received palmitic acid, Oil red O staining showed a decrease in the cellular content of fatty acid after incubation with docosahexaenoic acid (P < 0.05). PCR array indicated that the modulation of key genes played a role in atherosclerosis and reached near-control levels. These data support the notion that incubation of atherosclerotic human endothelial cells with docosahexaenoic acid could return the detrimental effects of palmitic acid by modulation of the atherosclerosis signaling pathway.

Docosahexaenoic acid reversed atherosclerotic changes in human endothelial cells induced by palmitic acid in vitro.

Abnormal activity of atherosclerotic endothelial cells paving luminal surface of blood vessels has been described in many diseases. It has been reported that natural polyunsaturated fatty acids such as docosahexaenoic acid exert therapeutic effects in atherosclerotic condition. Human umbilical vein endothelial cells were treated with 1mM palmitic acid for 48 hours and exposed to 40µM docosahexaenoic acid for the next 24 hours. Real-time polymerase chain reaction analysis was used to measure the expression of PTX3, iNOS, and eNOS. The level of nitric oxide was detected by Griess reagent. The transcription level of genes participating in coagulation and blood pressure was studied by polymerase chain reaction array. Docosahexaenoic acid improved the survival rate by reducing apoptosis rate (P < .05). Compared with that of the group given palmitic acid, attenuation of proinflammatory status was indicated by reduced interleukin-6 (P < .05) and prostaglandin E2 levels. All genes PTX3, iNOS, and eNOS were down-regulated after being exposed to docosahexaenoic acid. Nitric oxide contents were not changed in cells exposed to docosahexaenoic acid. Polymerase chain reaction array confirmed the reduction of LPA, PDGFß, ITGA2, SERPINE1, and FGA after exposure to docosahexaenoic acid for 24 hours (P < .05). Docosahexaenoic acid had potential to blunt atherosclerotic changes in the modulation of genes controlling blood coagulation, pressure, and platelet function. SIGNIFICANCE OF THE STUDY: The current experiment showed that docosahexaenoic acid could reverse atherosclerotic changes in human endothelial cells induced by palmitic acid. The increased levels of interleukin-6 and prostaglandin E2 in atherosclerotic cells were returned to near-to-normal status. Gene expression analysis showed a reduced activity of genes participating in atherosclerotic endothelial cells treated by docosahexaenoic acid. The expression of genes related to cell clotting activity was also similar to that of normal cells.

The autophagy paradox: A new hypothesis in neurodegenerative disorders.

A recent study showed that while autophagy is usually tied to protein and organelle turnover, it can also play dual roles in neurodegenerative diseases. Traditionally, autophagy was seen as protective since it removes damaged proteins and organelles. but new data suggests autophagy can sometimes promote neuron death. and This review tackles autophagy's seemingly contradictory effects in neurodegeneration, or the "autophagy paradox. " It offers a framework for understanding autophagy in neurodegenerative research and the cellular processes involved. In short, our data uncovers a harmful autophagy role in certain situations, conflicting the view that it's always beneficial. We describe the distinct, disease-specific autophagy pathways functioning in various neurodegenerative diseases. Part two concerns potential therapeutic implications of manipulating autophagy and current strategies targeting the autophagic system, suggesting interesting areas for future research into tailored modulators. This could eventually enable activating or controlling specific autophagy pathways and aid in developing more effective treatments. Researchers believe more molecular-level research is needed so patient-tailored autophagy-modulating therapeutics can be developed given this dilemma. Moreover, research must translate faster into effective neurodegenerative disease treatment options. This article aims to provide a wholly new perspective on autophagy's classically described role in these severe diseases, challenging current dogma and opening new therapeutic avenue options.

Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the accumulation of misfolded amyloid-beta and tau proteins. Autophagy acts as a proteostasis process to remove protein clumps, although it progressively weakens with aging and AD, thus facilitating the accumulation of toxic proteins and causing neurodegeneration. This review examines the impact of impaired autophagy on the progression of AD disease pathology. Under normal circumstances, autophagy removes abnormal proteins and damaged organelles, but any dysfunction in this process can lead to the exacerbation of amyloid and tau pathology, particularly in AD. There is increasing attention to therapeutic tactics to revitalize autophagy, including reduced caloric intake, autophagy-stimulating drugs, and genetic therapy. However, the translation of these strategies into clinical practice faces several hurdles. In summary, this review integrates the understanding of the intricate role of autophagy dysfunction in Alzheimer's disease progression and reinforces the promising prospects of autophagy as a beneficial target for treatments to modify the course of Alzheimer's disease.

Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model.

Introduction: Alzheimer's disease (AD) is the most common form of dementia worldwide. This study investigated the effects of lipopolysaccharide on neurosteroidogenesis and its relationship to growth and differentiation using SH-SY5Y cells. Methods: In this study, we used the MTT assay to assess the impact of LPS on SH-SY5Y cell viability. We also evaluated apoptotic effects using FITC Annexin V staining to detect phosphatidylserine in the cell membrane. To identify gene expression related to human neurogenesis, we utilized the RT2 Profiler TM PCR array human neurogenesis PAHS-404Z. Results: Our study found that LPS had an IC50 level of 0.25 µg/mL on the SH-SY5Y cell line after 48 h. We observed Aß deposition in SH-SY5Y cells treated with LPS, and a decrease in DHT and DHP levels in the cells. Our analysis showed that the total rate of apoptosis varied with LPS dilution: 4.6% at 0.1 µg/mL, 10.5% at 10 µg/mL, and 44.1% at 50 µg/mL. We also observed an increase in the expression of several genes involved in human neurogenesis, including ASCL1, BCL2, BDNF, CDK5R1, CDK5RAP2, CREB1, DRD2, HES1, HEYL, NOTCH1, STAT3, and TGFB1, after treatment with LPS at 10 µg/mL and 50 µg/mL. LPS at 50 µg/mL increased the expression of FLNA and NEUROG2, as well as the other genes mentioned. Conclusion: Our study showed that LPS treatment altered the expression of human neurogenesis genes and decreased DHT and DHP levels in SH-SY5Y cells. These findings suggest that targeting LPS, DHT, and DHP could be potential therapeutic strategies to treat AD or improve its symptoms.

Gene polymorphism of leptin and risk for heart disease, obesity, and high BMI: a systematic review and pooled analysis in adult obese subjects.

OBJECTIVES: Leptin polymorphism (LEP) has been associated with coronary heart disease (CAD), obesity, and high body mass index (BMI). However, we performed a systematic review and meta-analysis to discover the association because previous studies reached different conclusions. METHODS: Review Manager, version 5.3.5, and Stata, version 15.0, were used for statistical analysis. We calculated the effect size of the studies using the OR with the corresponding 95% CI, and two-sided (bilateral) p-values of 0.05 were considered significant. To determine heterogeneity among the selected studies, the Q test and I2 statistics were used. Meta-regression was used to examine the disease (heart disease, obesity, and high BMI) and heterogeneity between these subgroups. RESULTS: Eleven studies with 18,984 subjects were included in this study. The G-2548A (rs12112075), rs7799039, and A19G (rs2167270) polymorphisms of the leptin gene (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Our pooled analysis revealed an association between the G-2548A (rs12112075) polymorphism and heart disease, high BMI, and obesity. This indicates that individuals carrying the AA allele are at an increased risk for heart disease, high BMI, and obesity. People with heart failure and coronary artery disease did not have the rs7799039 polymorphism or its alleles linked to them. CONCLUSIONS: Combined analysis of data from current and published research suggests that the leptin gene polymorphisms G-2548A (rs12112075), rs7799039, and A19G (rs2167270) (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Further research is needed to understand this association.

Conditioned medium from amniotic fluid mesenchymal stem cells could modulate Alzheimer's disease-like changes in human neuroblastoma cell line SY-SY5Y in a paracrine manner.

BACKGROUND: Alzheimer's disease is usually diagnosed by significant extracellular deposition of beta-amyloid and intracellular neurofibrillary tangle formation. Here, we investigated the paracrine effect of amniotic fluid-derived mesenchymal stem cells on AD changes in human SH-SY5Y cells. METHODS: SH-SY5Y cells were divided into five groups: Control, 0.1 µg/ml LPS, 10 µg/ml LPS, 0.1 µg/ml LPS + conditioned medium, and 10 µg/ml LPS + conditioned medium. Cells were incubated with 0.1% and 10 µg/ml LPS for 48 h, followed by incubation with the conditioned medium of amniotic fluid-derived mesenchymal stem cells for the next 24 h. Beta-amyloid plaques were monitored by Congo-red staining. Survival and apoptosis were assessed by the MTT assay and flow cytometric analysis of Annexin-V. ELISA was used to measure the levels of neprilysin, angiotensin-converting enzyme, and Matrix Metalloproteinase-9. A PCR array was used to measure the expression of genes involved in neurogenesis. RESULTS: Bright-field imaging showed beta-amyloid plaques in the group treated with 10 µg/ml LPS. We found minimal effects in groups receiving 0.1 µg/ml LPS. The data showed that the reduction in the levels of neprilysin, angiotensin-converting enzyme, and Matrix Metalloproteinase-9 in the LPS-treated cells was attenuated after incubation with the stem cell secretome (p < 0.05). Amniotic fluid stem cell secretome increased the viability of LPS-treated SH-SY5Y cells (p 0.05) and was associated with a decrease in apoptotic changes (p < 0.05). We found the modulation of several genes involved in neurogenesis in the 10 µg/ml LPS + conditioned medium group compared to cells treated with 10 µg/ml LPS alone. CONCLUSION: Amniotic fluid stem cell secretion reduces AD-like pathologies in the human neuronal lineage.

Molecular mechanisms of sex hormones in the development and progression of Alzheimer's disease.

Alzheimer's disease (AD) is a form of brain disorder characterized by various pathological changes in the brain. Numerous studies have shown that sex hormones are involved in the disease. For instance, progesterone, estrogen, and testosterone are well-known steroid sex hormones that play an essential role in AD pathogenesis. The Gender-dependency of AD is attributed to the effect of these hormones on the brain, which plays a neuroprotective role. In recent years, much research has been performed on the protective role of these hormones against nerve cell damage, which are promising for AD management. Hence, in the current review, we aim to decipher the protective role of steroid hormones in AD. Accordingly, we will discuss their functional mechanisms at the genomic and non-genomic scales.

Calprotectin in inflammatory bowel disease.

The term IBD is usually used for referring to a group of inflammatory gastro-intestinal diseases (mainly Crohn's disease and ulcerative colitis). Accordingly, IBD arises as a result of inappropriate immune response to intestinal commensal organisms among genetically susceptible individuals. Performing colonoscopy and histopathologic evaluation on an inflamed bowel biopsy specimen are currently considered as gold standards for diagnosis and management of IBD. Correspondingly, these techniques are known to be invasive and costly. In recent decades, fecal calprotectin, as a biomarker, has received much attention for the diagnosis and non-invasive management of IBD. Up to now, many studies have investigated the efficacy of fecal calprotectin in the areas of IBD differentiation from IBS, prediction of endoscopic and histologic activities of IBD and prediction of disease recurrence. Although some of these studies have reported promising results, some others have shown significant limitations. Therefore, in this paper, we reviewed the most interesting ones of these studies after a brief discussion of the laboratory measurement of fecal calprotectin. Moreover, we attempted to provide an answer for the question of whether fecal-calprotectin could be considered as a potential surrogate marker for colonoscopy.

Evaluation of the Diagnostic and Predictive Value of Serum Levels of ANT1, ATG5, and Parkin in Multiple Sclerosis.

OBJECTIVE: Multiple Sclerosis (MS) is a disease of the central nervous system, which ultimately may lead to various disabilities in patients. No definitive cure has yet been developed for the disease. MRI is the method of choice for imaging MS plaques, which would be useful in disease diagnosis as it becomes progressive. Therefore, this study aimed to investigate the serum levels of ANT1 (adenine nucleotide translocase 1), ATG5 (autophagy-related protein 5), and Parkin in patients with MS, all of which play essential roles in MS pathophysiology, as novel serum biomarkers for early diagnosis of the disease. DESIGN AND METHODS: Forty patients in the early stages of the disease, and 40 healthy individuals were selected as the case and control groups. Upon sampling, the serum levels of the biomarkers were measured. RESULTS: The results indicated that autophagy, mitophagy, and mitochondrial apoptosis were different in the case and control groups. The oxidative stress level evaluation revealed low concertation of total antioxidant status (TAS) in the MS patients, while a partial increase accompanied the malondialdehyde (MDA). No significant correlation was observed between oxidative stress and autophagy or mitophagy factors. CONCLUSION: According to the results obtained from this study, the evaluation of serum levels of ANT1, ATG5, and Parkin could be applied in the diagnosis and follow-up of MS patients.

Association of Interleukin-1 and Inteleukin-1 Receptor Antagonist Gene Polymorphisms with Multiple Sclerosis in Azeri Population of Iran.

BACKGROUND: Cytokines as important mediators have a critical role in appropriate immune responses, the irregular production of which can lead to Multiple Sclerosis (MS). Proinflammatory cytokine interleukin-1 (IL-1) triggers inflammatory responses. Function and production of the cytokine are influenced by IL-1 coding gene polymorphism and those antagonists gene polymorphism. OBJECTIVE: The aim of the present study was to evaluate the possible correlation between MS and IL-1 related alleles in Azeri population of Iran. METHODS: Variable number tandem repeats (VNTR) genotypes of 150 MS patients and 220 healthy non-relative controls were determined. RESULTS: In the healthy controls, genotype TT at IL-1A (-889) location was significantly higher than the MS patients (p=0.0001). However, a significant difference was not found between the two groups in genotypic/allelic frequency at IL- 1B+ 3953 location. Evaluation of the IL-1RA gene revealed that genotype 1/2, and genotype 1/3 were significantly higher in the healthy controls and MS patients, respectively. Our findings indicated that the consumption of fast-food in MS patients was significantly higher than controls (p= <0.05). Also, a considerable number of MS patients had inappropriate dieting behaviors such as not eating breakfast (p= 0.0001), and irregular eating habits (p= 0.0001). CONCLUSION: Polymorphisms of the IL-1B genes and common alleles of IL-1RA were not considered as risk factors for MS disease. However, genotype TT at IL-1A (-889) location and the rare allele of IL-1RA3 can be a potential risk factor for the disease. Furthermore, inappropriate dieting behaviors and consumption of fast-food can increase the risk of MS.

Adjuvant therapy with stattic enriches the anti-proliferative effect of doxorubicin in human ZR-75-1 breast cancer cells via arresting cell cycle and inducing apoptosis.

Adjuvant therapy with novel and effective component has been presented as a contrivance in breast cancer treatment versus the conventional methods. The current research was done to evaluate the implement of stattic, specific STAT3 inhibitor on the anti-proliferative and apoptotic behavior of doxorubicin on ZR-75-1 breast cancer cells. Cell viability was investigated by MTT assay, the percentage of apoptosis by DAPI staining, and Annexin V. Real Time-PCR was applied to find out the correlation between mechanistic roles of the STAT3 pathway and apoptotic signal in the modulation of Bcl-2 and Bax gene expressions axis. The IC50 values for doxorubicin and stattic were 2.5 ± 0.18 µM and 3.5 ± 0.28 µM, respectively. Combination index (CI) value for ZR-75-1 breast cancer was 0.72, which indicated a strong synergistic effect. Incubation of the cells with a combination of stattic and doxorubicin revealed a significant increase in growth inhibitory effect of doxorubicin with more than 50% decrease in proliferation rate and a two-fold increase in the percentage of apoptotic cells. Assessment of gene expression levels demonstrated a visible decrease in antiapoptotic Bcl-2 and Bcl-xl accompanied by an increase in pro-apoptotic Bax mRNA levels (p < 0.05). Taken together, our results show that combination of a STAT3 inhibitor and doxorubicin can be figured out as a promising approach for dealing of patients with breast cancers.

Relationship between the use of electronic devices and susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune condition influenced by both genetic and environmental factors. Dirty electricity generated by electronic equipment is one of the environmental factors that may directly or indirectly impact MS susceptibility. The current Study aimed to evaluate the relationship between the usage time of electronic equipment and susceptibility to MS in North-West Iranian people. This approach was carried out upon 471 MS-diagnosed patients and 453 healthy participants as control group in East Province of Azerbaijan. By utilizing structured questionnaires, the information of all participants about usage status of some electronic devices was obtained. Data were analyzed by IBM SPSS Statistics version 18.0 and the quantitative variables were analyzed by Chi Square and Independent sample t tests. P values below or equal to 0.05 were considered as significant. Among the evaluated items in this approach, the utilization of cell phones and satellite television dishes were significantly higher in MS patients (p < 0.001, p = 0.07). Furthermore, a correlation was observed between sleeping with cell phone and/or laptop under the pillow (p = 0.011) and MS disease; however, there was no significant differences between MS patients and controls in computer using and television watching. Our study reinforces the concept that the utilization of some electronic devices and the continuous exposure to dirty electricity would increase the risk of MS disease thereupon by enhancing the cognizance of adverse effects of dirty electricity and reducing the time spent over electronic devices during adolescence and adulthood the occurrence probability of MS could be declined.

The Dynamics of Neurosteroids and Sex-Related Hormones in the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is commonly diagnosed by vast extracellular amyloid deposits and existence of intracellular neurofibrillary tangles. In accordance with the literature, age-related loss of sex steroid hormones in either males or females was found in relation to AD subjects. The dynamics of these hormones have been previously described in both physiological and pathological conditions with the evidence of changes in various intracellular signalings regarding the neurodegenerative disease. The potent protective effects of sex steroid hormones and their synthetic analogs are indicative of the decrease in the accumulated levels of intercellular beta-amyloid (Aß) protein and an increase of specific proteases activity, resulting in the improvement of pathological features. In the current review, we focused on the dynamic of signaling pathway related to sex steroid hormones. It is logical to hypothesize that androgen hormones have regulatory actions on the kinetics of Aß which make them as a promising preventive approach for neurodegenerative diseases in the near future.

Association of Promoter Polymorphisms of Interleukin-10 and Interferon-Gamma Genes with Tuberculosis in Azeri Population of Iran.

Promoter polymorphism of cytokine genes may lead to inter-individual differences in cytokine levels, therefore, polymorphisms may associate with susceptibility to infectious diseases. In this study, we investigated a possible association between interleukin-10 (IL-10) -1082A/G (rs1800896) and interferon (IFN)-gamma +874T/A (rs2430561) promoter polymorphisms and tuberculosis (TB) in the Azeri population of Iran. IL-10 -1082G/A and IFN-gamma +874T/A single nucleotide polymorphisms (SNPs) were genotyped by amplification refractory mutation system (ARMS)-PCR in 200 healthy controls and 124 tuberculosis patients. IL-10 -1082 A allele was more frequent in the control group than in the patient group (p=0.001, odds ratio [OR]=2.183). On the other hand, the AA genotype was significantly more frequent in the control group (p=0.0001). The frequency of IFN-gamma +874 T allele was significantly higher in the controls (p=0.013, OR=1.56). There was no significant association between IFN-gamma +874 T/A genotypes and susceptibility to tuberculosis (p=0.078), but TT genotype was more frequent in the control group. Our findings suggest that interleukin-10 -1082G/A polymorphism may play an important role in susceptibility to tuberculosis in our population. On the other hand, the +874T allele, which has been suggested to be associated with high IFN-gamma levels, was significantly higher in the controls and TT genotype was also more frequent in the control group. Thus, +874 T allele may be associated with resistance to tuberculosis in this Azeri population of Iran.

Correlation of Serum Levels of Vitronectin, Malondialdehyde and Hs- CRP With Disease Severity in Coronary Artery Disease.

INTRODUCTION: Vitronectin (VN), malondialdehyde (MDA) and high-sensitivity C-reactive rotein (hs-CRP) are cooperative agents involved in the atherosclerosis process. The study was conducted to assess the correlation of VN, MDA and hs-CRP with the severity of coronary artery disease (CAD). METHODS: Parameters such as serum VN, MDA and hs-CRP were measured in 250 subjects including 200 patients with angiographically diagnosed CAD (50 subjects with non-significant CAD, 50 with single vessel disease, 50 with double vessel disease, and 50 with triple vessel disease) and 50 CAD-free subjects as a control group. Serum VN was measured with ELISA; MDA was measured based on reaction with thiobarbituric acid (TBA); and hs-CRP level was measured by a Commercial Kit by Immunoturbidimetry. RESULTS: Serum VN, MDA and hs-CRP were significantly higher in patient groups compared to control group (P < .05). The mean value of MDA between 1 vessel and 3 vessel groups had significant difference (P = .01), also mean value of MDA between 2 vessel and control group and normal group showed significant difference (P < .001). The difference of MDA between 3 vessel and normal and 1 vessel and control group was significant (P < .001). CONCLUSION: The association and correlation between VN, MDA and hs-CRP indicate their involvement in the atherosclerosis process that may lead to progression of CAD. Also, these findings suggested that serum levels of VN, MDA and hs-CRP can help as diagnostic and monitoring markers in CAD patients and as markers of disease severity.