جستجوی مقالات مرتبط با کلیدواژه "integrin" در نشریات گروه "پزشکی"

Using histopathological and immunohistochemical methods, we aimed to examine the dose-dependent effects of chronic caffeine consumption on the recovery of burn wounds in an in vivo rat model.

Forty-five rats were randomly assigned to a high-dose group (20 mg/kg per day for eight weeks; n=15), a low-dose group (10 mg/kg per day for eight weeks; n=15), or a control group (n=15). The burn model was created in rats. The groups were separated into three subgroups (n=5) based on the day after injury (7th, 14th, or 21st day). The wound area, wound closure percentage, and histopathological and immunohistochemical reactivity were evaluated.

Successful wound healing was noted in rats treated with low doses of caffeine, similar to the control group. Pathology revealed low re-epithelization, low inflammation, and high granulation in the high-dose group. In addition, there was a significant difference between the control and high-dose groups regarding the immunohistochemical reactivity of αVβ3 integrin, VEGF, and MMP-9 (P<0.05).

We demonstrated that chronic caffeine consumption in rats adversely affects the recovery process of wounds in a dose-dependent manner. This effect may occur through delayed wound healing via the molecules MMP-9, αVβ3 integrin, and VEGF. Treatment that modulates these molecules can lead to enhanced and quicker recovery of damaged skin in coffee lovers.

Thyroid hormones are involved in the pathogenesis of various neurological disorders. Ischemia/hypoxia that induces rigidity of the actin filaments, which initiates neurodegeneration and reduces synaptic plasticity. We hypothesized that thyroid hormones via alpha-v-beta-3 (αvβ3) integrin could regulate the actin filament rearrangement during hypoxia and increase neuronal cell viability.

In this experimental study, we analysed the dynamics of actin cytoskeleton according to the G/F actin ratio, cofilin-1/p-cofilin-1 ratio, and p-Fyn/Fyn ratio in differentiated PC-12 cells with/without T3 hormone (3,5,3'-triiodo-L-thyronine) treatment and blocking αvβ3-integrin-antibody under hypoxic conditions using electrophoresis and western blotting methods. We assessed NADPH oxidase activity under the hypoxic condition by the luminometric method and Rac1 activity using the ELISA-based (G-LISA) activation assay kit.

The T3 hormone induces the αvβ3 integrin-dependent dephosphorylation of the Fyn kinase (P=0.0010), modulates the G/F actin ratio (P=0.0010) and activates the Rac1/NADPH oxidase/cofilin-1 (P=0.0069, P=0.0010, P=0.0045) pathway. T3 increases PC-12 cell viability (P=0.0050) during hypoxia via αvβ3 integrin-dependent downstream regulation systems.

The T3 thyroid hormone may modulate the G/F actin ratio via the Rac1 GTPase/NADPH oxidase/ cofilin1signaling pathway and αvβ3-integrin-dependent suppression of Fyn kinase phosphorylation.

Gastric cancer (GC) is considered one of the main reasons for cancer-related mortalities among Iranians. Kindlin-1 is an adhesion protein member of integrin-interacting proteins, regulating integrin activation through direct interaction with β-integrin. Therefore, kindlin-1 can be involved in the regulation of cell proliferation and adhesion. In the present study, we assessed the possible role of kindlin-1 in GC progression and metastasis.

 KINDLIN1 messenger RNA (mRNA) expression was assessed in tumor tissues from 80 GC patients in comparison with normal tissues using real-time polymerase chain reaction (PCR).

The levels of KINDLIN1 expressions were significantly correlated with sex (P=0.05) and tumor location (P=0.002). KINDLIN1 expression was also significantly associated with lymph node metastasis among the helicobacter pylori (HP)-negative cases (P=0.001). Moreover, a significant association between age and KINDLIN1 expression was observed among the HP-positive cases (P=0.039).

In the present study, we introduced KINDLIN1 as a location-specific marker for cardia gastric carcinoma. Moreover, it was observed that KINDLIN1 could be used as a sex-dependent diagnostic marker of GC patients.

This study examines the impact of integrin-linked kinase (ILK), protein kinase B (AKT), glycogen synthase kinase-3β (GSK-3β), and β-catenin signal molecules in SKOV-3 ovarian cancer cells adhered to fibronectin.  Expression levels of α4, αv, β1, and β6 integrin subunits known as the fibronectin ligand were investigated with the flow cytometry technique. The effects of ILK, AKT, GSK-3β, and β-catenin on the binding of SKOV-3 cells to fibronectin were examined by using the Real-Time Cellular Analysis (RTCA) method. Additionally, the interaction of these proteins was investigated by using Western blot analysis.  The results show that the expression levels of integrin subunits were ranked as αv (67.8%), followed by α4 (48.55%), β6 (32.05%), and β1 (31%) on SKOV-3 cells. RTCA results showed that ILK (10 µM Cpd22), GSK-3β (50 μM GSK-3β inhibitor-XI), AKT (35 µM FPA 124), and β-catenin (50 μM cardamonin) inhibitors decreased significantly (P<0.01) binding to fibronectin at 24 hr. Western studies in SKOV-3 cells adhered to fibronectin have shown that in inhibition of ILK, AKT expression was strongly inhibited, whereas, in the inhibition of AKT, ILK expression was strongly inhibited. Furthermore, the expression of β-catenin is partially reduced in inhibition of these two molecules. In β-catenin inhibition, AKT and ILK expressions are also strongly inhibited. ILK, AKT, GSK-3β, and β-catenin were found to be fundamental molecules in binding of SKOV-3 cells to fibronectin. ILK and AKT affect strongly the level of expression of each other, and both also affect the signal path of β-catenin.

Cell aggregation of threedimensional (3D) culture systems (the socalled spheroids) are designed as in vitro platform to represent more accurately the in vivo environment for drug discovery by using semi-solid media. The uniform multicellular tumor spheroids can be generated based on the interaction of cells with extracellular matrix (ECM) macromolecules such as collagen and integrin. This study aimed to investigate the possible interactions between the cellulose family and collagen using both in vitro and in silico approaches.

The 3D microtissue of JIMT-1 cells was generated using hanging drop method to study the effects of charge and viscosity of the medium containing cellulose family. To determine the mode of interaction between cellulose derivatives (CDs) and collagen-integrin, docking analysis and molecular simulation were further performed using open source web servers and chemical simulations (GROMACS), respectively.

The results confirmed that the addition of CDs into the 3D medium can promote the formation of solid spheroids, where methylcellulose (MC) yielded uniform spheroids compared to carboxymethyl cellulose (CMC). Moreover, the computational analysis showed that MC interacted with both integrin and collagen, while sodium carboxymethyl cellulose (NaCMC) only interacted with collagen residues. The stated different behaviors in the 3D culture formation and collagen interaction were found in the physicochemical properties of CDs.

Based on in vitro and in silico findings, MC is suggested as an important ECMmimicking entity that can support the semi-solid medium and promote the formation of the uniform spheroid in the 3D culture.

Aloe vera is used for its large variety of biological activities such as wound healing, anti-fungal, anti-inflammatory, hypoglycemic, immunomodulatory, gastroprotective, and anti-cancer. Although the beneficial effects of Aloe vera on wound healing have been proven, little is known about its effects at the cellular level. In this study, we evaluated the angiogenic and migrative effects of Aloe vera gel on fibroblasts and endothelial cells. Fibroblasts and endothelial cells were cultured in monolayer conditions with low glucose DMEM with 10% serum and 1% penicillin-streptomycin. Fresh and mature leaves of Aloe vera were used for gel preparation. Cell proliferation and morphology were studied by an inverted microscope. The migration of fibroblasts was assessed by scratch assay. MTT assay was performed for cell viability assessment, and real-time RT-PCR was used for evaluation of PECAM-1, integrin α1 and β1 transcription. After two days, the protein level of PECAM-1 was detected by flow cytometry. Our results showed that Aloe vera has a higher proliferative effect on fibroblasts in comparison with endothelial cells. Aloe vera also induced the migration of fibroblasts. The viability of both types of cells was similar to control ones. Integrin α1, β1 and PECAM-1 gene expression increased significantly (P < 0.005) in Aloe vera treated fibroblasts and endothelial cells in comparison with the control groups. However, the expression of these genes was significantly higher in fibroblasts in compareison with endothelial cells. Protein levels of PECAM-1 showed no change in both cell types upon Aloe vera treatment. Aloe vera gel induced angiogenic and cell adhesion properties in fibroblasts more than endothelial cells. Further investigations are needed to show the main role of fibroblasts rather than endothelial cells in wound healing by Aloe vera administration.

Asthma is an inflammatory airway disease and T helper 2 cytokines (i.e., interleukin 4, interleukin 5 [IL-5], and interleukin 13) have an important role in asthma pathology. Blood vessels in lung parenchyma and airway wall serve as the sources for inflammatory cells. The IL-5 leads to eosinophilic inflammation. The adhesion molecules on the endothelium and immune cells allow for the translocation of eosinophils. The vessels of the lung may play the main role in the cell migration and pathophysiology of asthma.

Several keywords were searched in databases, and out of 495 manuscripts 178 studies were selected. At least, 19 manuscripts were used as support of the above-mentioned hypothesis.

We hypothesized that airway vessels highly have leaks for eosinophils, and eosinophil migration from the endothelium of these vessels is easier than the endothelium of other tissues. Severe vascular leak and easy eosinophil migration in lung vessels cause inflammation leading to severe asthma phenotype; however, similar inflammation does not occur in other organs. The treatment of asthma is difficult and the control of cell migration needs to manipulate cell adhesion molecules.

The lung endothelial molecules may have the potential to develop new treatments for asthma.

Natural biomaterials are a key base in tissue engineering, and collagen, as the maincontent of the extracellular matrix (ECM), is frequently used in tissue engineering. Aloe verahas some therapeutic effects on ulcers, therefore, the use of this natural resource has alwaysbeen considered for improving collagen function. We aimed to evaluate the effect of Aloe vera/Collagen blended on cell viability, cell attachment, and angiogenic potential by determining ofintegrin α1β1 and platelet endothelial cell adhesion molecule (PECAM-1) genes expression inhuman adipose-derived stem cells (hASCs).

In this study, hASCs after harvesting of adipose tissues from abdominal subcutaneousadipose tissue and isolation, were cultured in four groups of control, collagen gel, Aloe veragel, and Aloe vera/collagen blended in vitro environment at 24h and then cell viability wasassessed by MTT (3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium) assay. Integrin α1β1 andPECAM-1 genes expression were evaluated by real-time RT-PCR.

The results of MTT showed that the combination of Aloe vera/collagen was retained thecell viability at the normal range and improved it. In real-time RT-PCR results, integrin α1β1 andPECAM-1 gene expression were increased in the Aloe vera/collagen blended group comparedto the control group.

For tissue engineering purposes, Aloe vera improves collagen properties in theculture of hASCs by increasing the expression of the integrin α1β1 and PECAM-1 genes.

It is well known that Arginine-Glycine-Aspartic acid (RGD) and Asparagine-Glycine- Arginine (NGR) peptides preferentially bind to integrin receptors and aminopeptidase N respectively and these two receptors play important roles in angiogenesis. Therefore ketoprofen as a non-selective cox Inhibitor was conjugated with linear RGD and NGR to take advantage of targeting capability of these two motifs and delivering ketoprofen to these cancer cells with overexpression of integrin and aminopeptidase N. In order to investigate the impact of possible steric hindrance due to the attachment of the drug to the peptide, a linear six carbon (hexanoic acid) linker was also used as a spacer. Cytotoxic effect of the synthesized compounds was evaluated against a group of cancer cell lines, including MCF-7, A2780 (αvβ3 positive), OVCAR3 (high αvβ3), HT-1-80 (high CD13) and SKOV-3 (CD13 positive). Both NGR and RGD conjugated forms of ketoprofen showed higher cytotoxic activity against OVCAR3 and HT-1-80 respectively.

Endometrial integrin expression changes might be a reason for implantation failure in polycystic ovarian syndromes (PCOS).

Assessment of integrin genes and proteins expression upon endometrium in the PCOS experimental mouse model was the main goal of this study.

30 NMRI female mice were equally divided into control, experimental (PCOS; received estradiol valerate (40 mg/kg)) and sham group (received; olive oil). After 8 weeks, each group was hyper stimulated by 7 IU PMSG and then, after 48hrs, 7 IU HCG was injected. Vaginal plaque was checked. After 5 days, Progesterone and estradiol levels and endometrial tissues were investigated to evaluate of α4, αv, β1 and β3 integrins gene and protein by qPCR method and immunohistochemistry, respectively.

Tissue samples were assessed and showed that level of progesterone was significantly decreased in PCOS group. Results of molecular part in the amount of αv, β3, β1 and α4 gene expressions showed a great difference in β3 and αv genes expressions between experimental groups. αv, β3, α4 and β1 proteins in the endometrial stroma in the control group were expressed, but they were not detected in PCOS group.

According to the results, integrins had different expression patterns in different areas of the endometrium; such as epithelial and stromal. It seems that in PCOS, this pattern has changed and the results might have a great influence on implantation failure. Therefore, this study suggests that a great attention to this problem may be essential in patients who are involved

It has been hypothesized that blastocyst integrin expression changes can affect the spontaneous miscarriage in polycystic ovarian syndromes (PCOS).

In this study, the profile of integrin genes and proteins was investigated on blastocyst of the PCOS experimental mouse model.

30 NMRI female mice were equally divided into 3 groups: control, experimental [PCOS that was injected estradiol valerate (40 mg/kg)]. After 8 weeks, each group was hyper stimulated by PMSG and HCG. Vaginal plaque was checked, and mice were investigated 5 days after the test. Progesterone and estradiol levels were determined; α4, αv, β1 and β3 integrin genes and protein of blastocysts were examined by real time PCR method and immunohistochemistry, respectively.

Estradiol level was significantly increased (p≤0.035) in PCOS group. Based on our finding, the ratio of gene's expressions αv, β3, β1 and α4 in PCOS to control group was 0.479±0.01, 0.5±0.001, 2.7±0.4 and 1.023±0.2 respectively. Genes expression showed a great difference (p≤0.001) between β3, β1 and αv in PCOS compared to other groups. αv and β3 integrin proteins expressed in all groups but intensity of these proteins in PCOS groups, was lower than other groups.

Pattern of αv and β3 integrins expression on the mouse blastocyst surface has an important effect during the implantation window. This pattern has changed in PCOS model and might have a great influence on implantation failure. Therefore, this experimental study suggests that a great attention to this problem may be essential in patients who are involved.

Inflammation of blood vessels is a characteristic feature of Kawasaki disease. Neutrophils play a key role in the inflammatory responses where movement of neutrophils toward the site of inflammation depends on CD11b/CD18 expression as adhesion molecules on these cells. The purpose of this study was to investigate CD11b/CD18 expression in patients with Kawasaki disease upon diagnosis and after treatment.The study included 20 children with Kawasaki disease aged from 3 months to 8 years. Mean fluorescence intensity of CD11b levels on diagnosis and at 1-2 and 6 weeks after intravenous immunoglobulin (IVIG) therapy was measured in these patients. Level of CD11b was measured in age-matched healthy children and febrile children (each 21) as negative and positive controls, respectively.Mean fluorescence intensity of CD11b in Kawasaki patients was lower than that of the control groups before and after 1-2 weeks of IVIG therapy. There were no significant differences in CD11b in Kawasaki patients either with aneurysm or without aneurysm.The CD11b levels at the diagnosis time and after treatment with IVIG in our patients with Kawasaki were lower than the control groups.