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Investigating the amount and activity of MMP2 and MMP9 in serum of heart valve replacement patients
referred to Imam Ali Hospital in Kermanshah.
The serum levels and activity of matrix metalloproteinases (MMPs) are associated with the risk of heart valve
calcification (HVC). We sought to investigate the association between MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs with MMP-2 and MMP-9 serum levels and activity in individuals with heart valve replacement (HVR). One hundred and fifty-five cases with HVR and 155 healthy individuals as control group from West of Iran were included and frequency of genotypes and alleles of rs243866 and rs3918242 in MMP-2 and MMP-9 genes were determined using PCR-RFLP. We also investigated the serum levels of MMP-2 and MMP-9 and their activity using ELISA and gelatin zymography, respectively. Additionally, serum biochemical parameters including FBS , urea, creatinine, cholesterol, triglyceride, HDL (high-density lipoprotein), LDL (low-density lipoprotein), calcium, and phosphorus as well as blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) were measured. Our results showed that both serum levels of MMP-2 and MMP-9 (P < 0.001) and their activity (P < 0.001) were higher in individuals with HVR when compared to the control group. Carrying A and T alleles in MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs, respectively, may predispose the individuals to HVC by acting as the risk factors. Serum levels and activity of MMP-2 and MMP-9 were found to be higher in HVR cases when compared to the healthy controls. Carriers of A allele in rs243866 SNP and T allele in rs3918242 SNP were shown to have higher MMP-2 and MMP-9 serum levels and activity that may result in increased ECM degradation and support the initiation and development of calcification.
Investigating the effect of sesquiterpene coumarins of Ferula assa-foetida on VEGF, MMP9, MMP2 and
studying the connection between them using computational methods and determining the effect of
substances on the induction of apoptosis in cell lines and the resulting oxidative stress.
Ferula assafoetida of Apiaceae family bears sesquiterpene coumarins from phenolic class. Studies have shown that
phenolic compounds at physiological concentration can inhibit two groups of gelatinase matrix metalloproteinases. So, the ability of compounds of this plant to inhibit the enzymes mentioned above seems to be useful. Acetone extract of plant was prepared and sesquiterpene coumarins were purified using column chromatography and HPLC preparative analyses and their structures were elucidated. After culturing the cell to proper confluence, the cells were isolated and the supernatant was removed. The pure substances were applied on cell lines U87MG and WEHI. In the computational part, the structure has been docked in the active site of metalloproteinase, and significant interactions were determined. Subsequently, ligand-protein complexes were subjected to molecular dynamics simulation in water and thermodynamic properties were calculated. In the phytochemistry field galbanic acid, mogoltadone, kellerin, polyanthin and polyanthinin were extracted from F. assafoetida. Biological investigation demonstrated significant changes in the amount and activity of matrix metalloproteinase and vascular endothelial growth factor. Ligand binding to the active site of the protein was studied in computational causing conformational changes in the active site of the protein. Investigation revealed that the coumrins have inhibitory effects on the content and activity of MMP 2&9 and showed anti-angiogenetic effect. So, they can be potentially effective in the treatment of cancer. Interactive and competitive binding between MMP-9 and galbanic acid were studied with FT-IR, UV-Vis and fluorescence methods and MMP-9 structure was changed in these interactions
Investigating the normal range of zinc in the urine of infants and healthy children in Kermanshah.
Zinc deficiency (ZnD) has adverse health consequences such as stunted growth. Since young children have
an increased risk of developing ZnD, it is important to determine its prevalence and associated factors in this population. However, only a few studies have reported on ZnD prevalence in young children from West of Iran. This study evaluated ZnD prevalence and associated factors, including dietary Zn intake, in healthy 1–3-year-old children from West of Iran. ZnD was defined as serum Zn concentration <9.9 µmol/L. A total of 278 children were included with a median age of 1.7 years (Q1–Q3: 1.2–2.3). The median Zn concentration was 11.0 µmol/L (Q1–Q3: 9.0–12.2), and ZnD prevalence was 31.3%. No significant differences were observed in the socio-economic characteristics between children with and without ZnD. Dietary Zn intake was not associated with ZnD. ZnD is common in healthy 1–3-year-old children from West of Iran. However, the use of currently available cut-off values defining ZnD in young children has its limitations since these are largely based on reference values in older children. Moreover, these values were not evaluated in relation to health consequences, warranting further research.
Comparative investigation of selenium levels in maternal blood and umbilical cord in premature and full-
term infants.
Selenium is an essential trace element and has a main role in cellular antioxidant defense system. In very preterm
babies, low selenium is associated with an increased risk of complications such as chronic neonatal lung disease and retinopathy of prematurity. This study was designed to determine and compare maternal and umbilical cord blood selenium levels in term and preterm infants. From January 2019 to December 2019, 30 term (gestational age>37 weeks) and 30 preterm infants (gestational age<34 weeks) and their mothers were enrolled. Selenium concentrations in umbilical cord and maternal venous blood were measured by atomic absorption spectrometry. The mean selenium concentration in term infants was higher than in preterm infants (124.80+/-13.72 microg/L vs 100.30+/-11.72 microg/L, P=0.0001). The mean selenium concentration in mothers of term and preterm infants was not significantly different (117.03+/-17.15 microg/L vs 110.56+/-17.49 microg/L, P=0.15). Cord selenium concentrations were strongly correlated with gestational age and birth weight (r=0.66, p<0.0001 and r=0.59, p<0.0001, respectively) when the data of all infants were analyzed together. None of the 60 women had a serum selenium level below the laboratory lower limit of normal (70.0 microg/L). Maternal selenium levels were correlated with cord selenium levels in their infants (r=0.40, p<0.001) when data of all newborn infants and mothers were considered together.
Investigating effects of temozolomide on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9,
VEGF, anti-proliferatory cytotoxic and apoptotic properties.
Temozolomide is an alkylating agent which is used in glioblastoma treatment. We aimed to investigate the effects of
different concentrations of temozolomide and exposure time on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9 and VEGF. U87MG cells were cultured in different temozolomide concentrations and incubation time and the effects of temozolomide on inducing apoptosis was investigated. The levels of VEGF and CXCR4 expression were measured by RT-PCR and flowcytometry. Moreover, MMP2 and MMP9 activity and expression were assessed by ELISA and zymography. CXCR4 and VEGF expression levels decreased upon applying higher concentration of temozolomide. MMP2 and MMP-9 had lower activity in cells with longer exposure time or higher doses of temozolomide. Temozolomide induces the apoptosis in U87MG glioblastoma cells at therapeutic or higher dose. It is capable of decreasing their expression levels of VEGF and CXCR4.
Investigating effects of prantschimgin and grandivitin from Ferulago macrocarpa on VEGF, MMP9,
and MMP2.
Ferulago macrocarpa contains prantschimgin and grandivitin from phenolic class. Studies have shown that phenolic
compounds at physiological concentrations could inhibit two groups of gelatinase matrix metalloproteinases (MMP2, MMP9). Due to the high diversity of coumarin in the plant, the possibility ability of the compounds to inhibit plant enzymes seem to be mentioned. Ferulago macrocarpa of Apiaceae, native to the highlands of the West of Iran (Zagros Mountains) includes Prantschimgin and Grandivitin from phenolic class. researches have shown that phenolic compounds at physiological concentrations could prevent two groups of gelatinase matrix metalloproteinases (MMP2, MMP9). Because of the high variety of coumarin in the plant, the potency of the compounds to inhibit plant enzymes seem to be refered. Acetone extract of the plant was provided and then winterized. Thereafter, Prantschimgin and Grandivitin were purified using normal phase column chromatography and preparative HPLC, and their structures were verified. After culturing the cells, at confluence step, Supernatants were collected at24 and 48h soup (broth supernatant containing medium containing 2% albumin, and glutamine and antibiotics and enzymes secreted by the different concentrations of active ingredients) and non-proliferation medium containing 2% albumin was amplified. The pure substances were applied on cell lines U87MG and Wehi for evaluation of VEGF, MMP-2 and 9 activities. Prantschimgin and grandivitin were purified from F.macrocarpa fruits. Regarding cytotoxicity results IC50 of Prantschimgin and Grandivitin in Wehi cell line were 521.63, 232.66, and in U87MG cell line were 575.58, 322.0 lpg/ml, respectively. Biological experiment indicated significant changes in the amount and activity of matrix metalloproteinase and vascular endothelial growth factor. The application can be expected to have therapeutic efficacy in cancer cell lines U87MG and Wehi.
The study of Livergol® effect on serum levels of MMP2, MMP9 and VEGF in Rheumatoid Arthritis Patients.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that characterized by pain which can lead to joint
destruction and disability. Activation of complements will cause cytokine production such as TNF-a, MMP-2, MMP-9 and VEGF, and this will make the disease to start or to progress to destruction and deformity of joint. Several classes of drugs are used in treatment of RA which some are useful only to control acute symptoms, However, they have numerous. Milk thistle extract (Silymarin) does have so strong antioxidant and anti- inflammatory effects that it made us to study its effect as an adjunct to DMARDs in treatment of patients with RA. 42 RA patients with a two years history of the disease, who were matched in their drugs used to treat, participated in this study. They underwent a three months trial of treatment with LIVERGOL, which contain Silymarin, 140 mg thrice a day, as an adjunct to DMARDs used by the patient. Fasting venous blood sample was obtained from all patients; serum was aliquoted and stored at -70oC until evaluation. Serum level of MMP-2 and MMP-9 and VEGF were measured before and after intervention by Elisa Kit. To analyze the data, we used Paired-Samples and Wilcoxon tests. In comparison to before treatment with Livergol, there was a significant decrease in serum level of MMP-2 and VEGF in RA patients after 90 days' administration of livergol . Our findings show that silymarin can significantly reduce serum levels of MMP-2 and VEGF RA patients after 90 days administration of Livergol. The exact mechanism of therapeutic effects of Silymarin in RA patients is not clear but it can be result of its anti-inflammatory and anti-oxidative properties.
In-vitro cytotoxicity assessment of N-(5-(Benzylthio)-1, 3, 4-thiadiazol-2-yl)-2-(4-(trifluoromethyl) phenyl) acetamide with potential anticancer activity.
Cancer is the second leading cause of death in the world. Despite advances in the diagnosis and treatment, overall
survival of patients still remains poor. Hence, there is an urgent need for development of new anticancer agents. Considering promising biological activity of 1,3,4-thiadiazole derivatives, in the present study, synthesis and cytotoxicity assessment of new derivatives of this ring was done. All synthesized compounds were characterized by NMR, IR and MS spectroscopic methods. Obtained data from MTT assay showed that all compounds 3a- 3l had better anticancer activity against MDA(breast cancer) compared to PC3(prostate cancer) and U87(Glioblastoma). Compound 3 g with m-OCH3 moiety on the phenyl ring was the most potent one in this series with IC50 = 9 μM against MDA breast cell line in comparison with imatinib (IC50 = 20 μM) as reference drug.