Non-coding RNAs are correlated to TGF-ß receptor type 2 in patients with colorectal cancer.

BACKGROUND: Multiple molecular expression alterations, particularly in non-coding RNAs, play fundamental roles in the regulations of cellular processes and may relate to the occurrence and progression of colorectal cancer (CRC). In the present study, we investigated the associations between TGFBR2, miR20a-5p and long non-coding RNA (lncRNA) LAMTOR5-AS1 in CRC patients. METHODS: Colorectal cancer and adjacent normal tissue samples (n = 34) were prepared from CRC patients. The associations between TGFBR2, miR20a-5p and lncRNA LAMTOR5-AS1 were predicted using bioinformatics tools. The expression levels of TGFBR2, miR20a-5p and lncRNA LAMTOR5-AS1 were measured using a quantitative real-time polymerase chain reaction technique. The TGFBR2 protein values were measured by western blotting. The clinical importance of lncRNA LAMTOR5-AS1 was assessed using receiver operating characteristic curve. RESULTS: The up-regulated levels of TGFBR2 (p = 0.02), TGFBR2 protein (p = 0.008) and lncRNA LAMTOR5-AS1 (p = 0.02) were significantly observed in CRC tissues compared to the adjacent normal tissues. The miR20a-5p expression level (p = 0.009) was downregulated in CRC tissues. In addition, the miR20a-5p expression level was inversely correlated to the TGFBR2 gene (r2  = 0.88, p < 0.0001), protein (r2  = 0.95, p < 0.0001) and lncRNA LAMTOR5-AS1 gene (r2  = 0.93, p < 0.0001) expression levels. Based on the area under curve, the increase of lncRNA LAMTOR5-AS1 expression level with a sensitivity of 64.52% and specificity of 65.52% was considered in CRC patients. CONCLUSIONS: We propose that miR20a-5p is inversely related to long non-coding RNA (lncRNA) LAMTOR5-AS, such that it may be involved in the regulation of TGFBR2 expression level in CRC patients.

Laterality dissociation of ventral hippocampus inhibition in learning and memory, glial activation and neural arborization in response to chronic stress in male Wistar rats.

Many studies suggest that animals exhibit lateralized behaviors during stressful situations. However, which brain structure in each hemisphere underlies such lateralized function is unclear. This study, investigated the effects of bilateral and unilateral inhibition of the ventral hippocampus (VH) on chronic restraint stress (CRS) induced memory impairment. Unilateral and bilateral VH cannulation was carried out. After a week of recovery, lidocaine hydrochloride was injected into the rat VH ten minutes before CRS induction for seven consecutive days. Behavioral (Y-maze and Morris water maze; MWM)), and histological (glial fibrillary acidic protein; GFAP, ionized calcium-binding adapter protein-1; Iba-1, as well as Golgi-Cox staining in the VH) studies were performed. The result showed no significant difference between the effect of right-only and left-only of VH inhibition induced by lidocaine on spatial learning and memory and working memory. In addition, lidocaine treated groups were significantly lower in spatial learning and memory and working memory than control groups during non-stress conditions. Furthermore, the dendritic arborization in the right-only, left-only and bilateral VH microinjected lidocaine significantly decreased after the CRS condition compared with the control group. However, lidocaine microinjection resulted in up-regulation levels of GFAP and Iba1 in the right-only, left-only and bilateral of VH and they were higher significantly than that of their control groups after CRS and during non-stress condition. Meanwhile, there is no significant difference between the effect of right-only and left-only of VH inhibition on neuronal arborization and glial cells during non-stress and after the CRS condition. In conclusion, bilateral VH inhibition can give rise to increase CRS-induced memory impairment. These findings were accompanied by elevating GFAP and Iba1 while reducing the dendritic arborization.

Atopic dermatitis: molecular, cellular, and clinical aspects.

Atopic dermatitis (AD) is a complicated, inflammatory skin disease, which numerous genetic and environmental factors play roles in its development. AD is categorized into different phenotypes and stages, although they are mostly similar in their pathophysiological aspects. Immune response alterations and structural distortions of the skin-barrier layer are evident in AD patients. Genetic makeup, lifestyle, and environment are also significantly involved in contextual factors. Genes involved in AD-susceptibility, including filaggrin and natural moisturizing, cause considerable structural modifications in the skin's lipid bilayer and cornified envelope. Additionally, the skin's decreased integrity and altered structure are accompanied by biochemical changes in the normal skin microflora's dysbiosis. The dynamic immunological responses, genetic susceptibilities, and structural modifications associated with AD's pathophysiology will be extensively discussed in this review, each according to the latest achievements and findings.

Blockade of TGF-ßR improves the efficacy of doxorubicin by modulating the tumor cell motility and affecting the immune cells in a melanoma model.

TGF-ß contributes to drug resistance and the invasiveness of tumor cells and weakens the anti-tumor immune responses. The present study aimed at examining the efficacy of the combination of SB431542, as a specific inhibitor of TGF-ßR, and doxorubicin in controlling the melanoma tumor in mice. The impact of the combination of the doxorubicin and SB431542 on the cell growth, apoptosis, migration, and invasiveness of B16-F10 cells was examined. Besides, the B16-F10 tumor was induced in C57BL/6 mice, and the effects of the mentioned treatment on the tumor volume, survival, and the exhaustion state of T cells were evaluated. Although the combination of doxorubicin and SB431542 did not exhibit synergism in the inhibition of cell growth and apoptosis induction, it efficiently prohibited the migration and the epithelial to mesenchymal transition of B16-F10 cells, and the combination of doxorubicin and SB431542 caused an increase in mRNA levels of E-cadherin and, on the other hand, led to a decline in the expression of Vimentin. Tumor volume and the survival of tumor-bearing mice were efficiently controlled by the combination therapy. This treatment also eventuated in a decrease in the percentage of PD-L1+, TCD4+, and TCD8+ cells as indicators of exhausted T cells within the spleens of tumor-bearing mice. Blockade of TGF-ßR also propelled the RAW 264.7 cells towards an anti-tumor M1 macrophage phenotype. The inhibition of TGF-ßR demonstrated a potential to increase the efficacy of doxorubicin chemotherapy by the means of affecting cellular motility and restoring the anti-tumor immune responses.

Prospects for Manipulation of Mesenchymal Stem Cells in Tumor Therapy: Anti-Angiogenesis Property on the Spotlight.

The interactions between the tumor microenvironment and the tumor cells confers a condition that accelerate or decelerate the development of tumor. Of these cells, mesenchymal stem cells (MSCs) have the potential to modulate the tumor cells. MSCs have been established with double functions, whereby contribute to a tumorigenic or anti-tumor setting. Clinical studies have indicated the potential of MSCs to be used as tool in treating the human cancer cells. One of the advantageous features of MSCs that make them as a well-suited tool for cancer therapy is the natural tumor-trophic migration potential. A key specification of the tumor development has been stablished to be angiogenesis. As a result, manipulation of angiogenesis has become an attractive approach for cancer therapy. This review article will seek to clarify the anti-angiogenesis strategy in modulating the MSCs to treat the tumor cells.

Avocado/soy unsaponifiables can redress the balance between serum antioxidant and oxidant levels in patients with osteoarthritis: a double-blind, randomized, placebo-controlled, cross-over study.

OBJECTIVES: Osteoarthritis (OA) is an inflammatory disorder of the joint characterized by pain and stiffness. Oxidative stress plays an important role in pathogenesis of OA. We aimed to evaluate the effects of avocado/soy unsaponifiables (ASU) compound on serum antioxidant and oxidative stress in patients with Osteoarthritis. METHODS: A double-blind, randomized, placebo-controlled, cross-over trial was performed. Fourty patients with osteoarthritis were randomized to two different sequences: 1) DP: received ASU for three months followed by three months placebo, 2) PD: received placebo for the first three months followed by three months ASU. The oxidant statue was evaluated by measurement of serum malonldialdehyde (MDA). The total antioxidant capacity (TAC), reduced glutathione (GSH) and antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were also assessed. RESULTS: Mean serum of MDA level as a marker of oxidative stress significantly decreased in all patients after three months treatment with ASU (4.46 ± 0.11 nmol/L) compare with baseline and placebo levels (5 ± 0.15 and 5.82 ± 0.12 nmol/L respectively) (p<0.05). On the other hand, ASU resulted in positive changes in serum antioxidant levels (p<0.05). Mixed-effects model of variance analyses showed that ASU effect is regardless of the order of receiving medication (p>0.05). CONCLUSIONS: These data showed that Avocado/Soy Unsaponifiable can be an effective supplement in treatment of osteoarthritis through the control of the balance between antioxidant and oxidant molecular markers.

The Effect of Aqueous Extract of Trachyspermum ammi Seeds and Ibuprofen on Inflammatory Gene Expression in the Cartilage Tissue of Rats with Collagen-Induced Arthritis.

BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) is an inflammatory disease treated with nonsteroidal anti-inflammatory drugs that have different side effects. One of the plants used for this purpose in the traditional medicine is Trachyspermum ammi. The present study aimed at investigating the anti-inflammatory effect of this plant on type II collagen-induced arthritis (CIA) in Wistar rats. MATERIALS AND METHODS: The study was performed on 35 male Wistar rats. Seven rats were considered as the healthy control group (normal group), and CIA was stablished in the rest. The rats with a model of inflammatory arthritis were divided into four groups. One group did not receive any treatment and three groups were treated orally with ibuprofen (15 mg/kg), aqueous extract of the T. ammi seeds (100 mg/kg), or their combination for 30 days. The effect of different treatments was investigated on the paw thickness, arthritis score, and mRNA level of COX2 and iNOS genes. RESULTS: CIA increased paw thickness, arthritis score, and COX2 and iNOS mRNA levels compared to those of the normal group. Treatment with ibuprofen and aqueous extract alone or in combination reduced the studied variables. Reduction in the paw thickness, arthritis score, and iNOS mRNA level was more in the ibuprofen-treated group than the T. ammi extract-treated group, but treatment with T. ammi extract reduced COX2 mRNA level more than ibuprofen. CONCLUSION: It seems that the aqueous extract of T. ammi can be used alone or in combination with ibuprofen to treat RA.

Composite Nanoscaffolds Modified with Bio-ceramic Nanoparticles (Zn2SiO4) Prompted Osteogenic Differentiation of Human Induced Pluripotent Stem Cells.

Nanofiber scaffolds and bio-ceramic nanoparticles have been widely used in bone tissue engineering. The use of human- induced pluripotent stem cells (hiPSCs) on this scaffold can be considered as a new approach in the differentiation of bone tissue. In the present study, a polyaniline-gelatin-polycaprolactone (PANi-GEL-PCL) composite nanoscaffold was made by electrospinning and modified superficially by plasma method. The synthesized nanoscaffold was then coated with willemite's bio-ceramic nanoparticles (Zn2SiO4). The nanoscaffold's properties were studied by scanning electron microscopy (SEM). Also, nanoparticles characterization was carried out with SEM and dynamic light scattering. The growth and proliferation rate of cells on the synthesized nanoscaffold was examined by MTT assay. Subsequently, hiPSCs were cultured on murine fibroblast cells, incubated in embryoid bodies for 3 days, and placed on the nanoscaffolds. The differentiation potential of hiPSCs was investigated by the examination of common bone markers (e.g. alkaline phosphatase, calcium salt precipitation, and alizarin red test) using bone differentiation factors for 14 days. SEM showed the proper structure of electrospinned nanoscaffolds and coating of nanoparticles on the nanoscaffold surface. The results of MTT assay confirmed the growth and proliferation of cells and the biocompatibility of nanofibers. The results of bone indices also showed that differentiation on the composite nanoscaffold coated with willemite's bio-ceramic nanoparticles dramatically increased in comparison with other groups. Overall, this study demonstrated that PANi-GEL-PCL composite nanoscaffold with willemite's bio-ceramic nanoparticles is a suitable substrate for in vitro growth, proliferation, and differentiation of hiPSCs cells into osteoblasts.

17ß-Estradiol Stimulates Generation of Reactive Species Oxygen and Nitric Oxide in Ovarian Adenocarcinoma Cells (OVCAR 3).

BACKGROUND: Experimental and epidemiological evidence supports a role for steroid hormones in the pathogenesis of ovarian cancer. Among steroid hormones, 17ß-estradiol (E2) has the most potent effect on proliferation, apoptosis and metastasis. OBJECTIVES: In the present study, we investigated the effect of E2 on production of ROS and NO in ovarian cancer cells. MATERIALS AND METHODS: Ovarian adenocarcinoma cell line (OVCAR-3) was cultured and treated with various concentrations of E2, antioxidants (N-acetyle cysteine and Ebselen) and ICI182780 as an estrogen receptor antagonist. MTT test was performed to evaluate cell viability. NO and ROS levels were measured by Griess and DCFH-DA methods, respectively. RESULTS: ROS levels as well as NO levels were increased in OVCAR-3 cells treated with E2. The increase in ROS production was in parallel with increased cell viability which indicates that estrogen-induced ROS can participate in cancer progression. ICI182780 abolished E2-induced ROS production. Progesterone was also effective in reducing ROS and NO generation. CONCLUSIONS: NO and ROS are important molecules in signaling networks in cell. These molecules can be used as therapeutic targets for prevention and treatment of ovary cancer and other estrogen-induced malignancies.

Association Between Genetic Variants of Akt1 and Endometrial Cancer.

Akt isoforms have critical roles in the cause and regulation of cancer cells invasive, migration, and metastatic dissemination. In the present study, the association between Akt1 polymorphisms and endometrial cancer was investigated in patients with endometrial cancer and controls. Thirty premenopaused patients diagnosed with endometrial cancer and 30 premenopaused women with no clinically documented abnormalities of the endometrium undergoing hysterectomy were included in this study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. There was no significant difference between Akt1 gene polymorphisms of patients (SNP1, SNP2 and SNP3) with endometrial cancer and controls (p > 0.05). Difference between alleles frequency of SNP1, SNP2, SNP3 of patients with endometrial cancer and controls was not significant (p > 0.05). SNPs (rs72715985), (rs2494750), and (rs74090038) of Akt1 gene are not associated with endometrial cancer in Iranian subjects.

The evaluation of the FOXO1, KLF9 and YT521 genes expression in human endometrial cancer.

BACKGROUND: The current study was designed to explore the changes of the mRNA levels of the YT521, Forkhead box protein O1 (FOXO1), and Krüppel-like factor 9 (KLF9) proteins in human normal and cancerous endometrial tissue. METHODS: The study was conducted in 30 premenopausal patients diagnosed with endometrial cancer and 20 premenopausal women with no clinically documented abnormalities of the endometrium undergoing hysterectomy. Gene expression levels were assayed using quantitative real-time PCR. RESULTS: The endometrial tissue FOXO1 mRNA level (0.82 +/- 0.27) of patients with endometrial cancer was significantly lower (p < 0.001) than controls (4.51 +/- 2.68). In subjects with endometrial cancer the KLF9 mRNA level (1.12 +/- 0.38) was lower (p < 0.001) when compared to controls (3.11 +/- 1.52). A remarkable (not significant, p = 0.069) increase was found in the YT521 mRNA level of patients' endometrial tissue (11.19 +/- 3.99) in comparison with the control subjects (8.82 +/- 5.01). No significant difference was detected for the FOXO1, KLF9 and YT521 mRNA levels of the endometrial tissue of patients with cancer at different stages. CONCLUSIONS: It is suggested that the alteration of the gene expression profiles of FOXO1, KLF9 and YT521, which occur in human endometrial cancers likely play a crucial role in initiation of cancer.

Distribution of fatty acids in adipose tissue of patients with type 2 diabetes.

BACKGROUND: It is not known whether alterations of adipose tissue fatty acid compositions predict type 2 diabetes. Our goal was to characterize the relationship between the adipose tissue fatty acid compositions and type 2 diabetes. METHODS: We evaluated the fatty acid compositions of subcutaneous adipose tissue. These analyses were carried out on samples from 76 normal and 98 diabetic adults. Analysis was performed on a gas chromatograph. RESULTS: The adipose tissue palmitic acid composition of diabetic subjects (24.9% +/- 0.3) was significantly higher (p = 0.01) than in the controls (23.3% +/- 1.6). A significant negative correlation (r = -0.276, p = 0.001) was found between adipose tissue polyunsaturated fatty acids (PUFAs) and the Chol/HDL-C ratio of all the subjects studied (controls plus diabetic patients). A similar negative correlation (r = -0.429, p = 0.001) was identified only for control group, whereas no significant correlation (p > 0.05) was found for diabetic populations. The correlation between fatty acid compositions and serum lipid profiles (TG, HDL-C, Chol/HDL-C, LDL-C/HDL-C proportion) and fasting blood sugar (FBS) with HbAlc concentrations of people with diabetes and controls was not significant. CONCLUSIONS: A high amount of palmitic acid in adipose tissue may increase the risk of the type 2 diabetes and it seems that a high intake of PUFAs can lead to lowering of the Chol/HDL-C ratio.

Adiponectin, leptin and lipid profiles evaluation in oral contraceptive pill consumers.

BACKGROUND: The aim of this study was to evaluate serum lipid profiles, leptin and adiponectin levels in women with a normal menstrual cycle receiving low-dose (LD) combined oral contraceptive pill (COC) (levonorgestrel 0.15 mg, ethinyl-estradiol 0.03 mg). STUDY DESIGN: Serum adiponectin and leptin concentrations were measured by enzyme-linked immunosorbent assay (ELISA), and spectrophotometric assay was used for serum lipid and lipoprotein profiles assay in 50 healthy women with normal menstrual cycles who served as the control group and 50 women taking COCs. Unpaired t test and Chi-square test were used for comparison of variables between oral contraceptive users and non-oral contraceptive users. RESULTS: Serum adiponectin and leptin levels were changed in COC consumers. The data obtained for adiponectin in COC consumers (6.6 ± 4.06 µg/ml) were significantly lower (-27.4%, P = 0.004) than control group (9.1 ± 5.09 µg/ml). The difference between the serum leptin concentration of the control group (11.5 ± 6.9 ng/ml) and women receiving COCs (14.1 ± 6.7 ng/ml) was not significant (+18.4%, P = 0.083). There was nonsignificant difference between HDL levels of subjects taking COC (44.02 ± 10.7 mg/dl) and control group (49.4 ± 14.3 mg/dl). The LDL levels of COC consumer (131.40 ± 66.40 mg/dl) was significantly higher (P = 0.002) than controls (102.30 ± 44.0 mg/dl). The serum cholesterol concentration of women receiving COC (193.2 ± 70.4 mg/dl) was significantly higher (P = 0.05) than controls (172.8 ± 49.6 mg/dl). The age of COC consumption and the duration of intake of COCs beyond 36 months had no significant effect on the adiponectin and leptin concentrations. CONCLUSION: LD COC uptake results in a significant decrease in serum adiponectin concentration, nonsignificant increase in leptin levels and a more atherogenic lipid profile by significantly increasing LDL and nonsignificantly decreasing HDL concentrations. These findings suggested that COC may reduce or stimulate the adiponectin and leptin concentrations, respectively. This might be due to an effect of these pills on adipocyte maturation via inhibition or stimulation of the synthesis of new adiponectin and leptin molecules or may be a result of the increased frequency of a particular allele of the adiponectin and leptin. It is suggested that these alterations in adiponectin and leptin concentrations and lipid profiles may be related to their probable effects in response to various pathological and physiological properties of COC or its metabolites. It seems that probably free radicals produced during metabolism of COCs change the amounts of adipokines and atherogenic lipids.

Fatty acid composition of serum lipids in patients with type 2 diabetes.

BACKGROUND: Serum fatty acid content mainly reflects dietary fat intake. It is not known whether alterations of serum fatty acid compositions predict type 2 diabetes risk. METHODS: We evaluated fatty acid contents in serum of the 76 normal and 98 diabetic adults taking part in a cross sectional study, using a gas chromatography method. RESULTS: The contents of total saturated (SFAs) and monounsaturated fatty acids (MUFAs) of the diabetic subjects were significantly higher when compared to the controls (p = 0.006, p = 0.02 respectively). Serum linoleic and polyunsaturated fatty acid (PUFAs) contents of subjects with diabetes were significantly lower than the control group (p = 0.02). There was a negative correlation (p = 0.001, r = -0.429) between serum PUFAs contents and cholesterol/HDL-C ratio in the control group, whereas this correlation in people with diabetes was not significant (p = 0.12). The correlation between serum TG (triglyceride) and SFAs contents of the diabetic patients was significantly positive (p = 0.01, r = 0.252). A significant negative correlation (p = 0.001, r = -0.421) was found between PUFA contents and serum TG levels of people with diabetes; however, the same correlation for the control group was not significant (p = 0.56). CONCLUSIONS: Diabetes incidence was significantly and positively associated with the proportions of serum palmitic, total saturated and monounsaturated fatty acid contents. Our findings with the use of this biomarker suggest that the dietary fat profile, particularly that of saturated and monounsaturated fatty acids, may contribute to the etiology of diabetes. It seems that patients with type 2 diabetes can have good control on lipid parameters with a higher intake of polyunsaturated fatty acids than saturated fatty acids.

Effect of oral contraceptive therapy on homocysteine and C-reactive protein levels in women: an observational study.

OBJECTIVE: Increased levels of homocysteine and C-reactive protein (CRP) are considered as independent risk factors for atherosclerosis. As the level of these factors is affected by sex hormones, a population-based assessment of their changes following oral contraceptive therapy is needed to avoid the side effects that might arise of these variations. To this aim, the present study was to investigate the effect of combined oral contraceptive (OCP) on CRP and homocysteine levels among young healthy women. METHODS: We conducted an observational cross-sectional analysis of 90 healthy, non-obese women (mean age 25 years and body-mass index 22 kg/m2). Forty-five healthy women on OCP and 45 healthy controls were studied for CRP and homocysteine levels by enzyme-linked immunosorbent assay (ELISA). Unpaired t test and Chi-square test were used for comparison of variables between oral contraceptive users and non-oral contraceptive users. RESULTS: The results showed that the homocysteine (13.268±3.475 vs. 7.288±2.621 µmol/L) and CRP (5863.0±1349.5 vs. 1138.3±691.12 ng/ml) levels were significantly higher in women receiving OCP in comparison with the control group (p=0.027 and p<0.001, respectively). CONCLUSION: The alteration in homocysteine and CRP levels could be attributed to the OCP suggesting that use of these pills should be reviewed in women with increased risk of atherosclerosis and other cardiovascular risk factors.