جستجوی مقالات مرتبط با کلیدواژه "mmp-9" در نشریات گروه "پزشکی"

Sulfur mustard (SM) is a potent blistering agent. This alkylating chemical agent has extremely toxic effects on the eye. MMP-2 and MMP-9 are the two most important matrix metalloproteinase enzymes involved in the pathology of chemical eye injuries. Curcumin is regarded as a natural anti-inflammatory agent. This study aims to compare the anti-inflammatory effects of curcumin versus doxycycline on chemically induced corneal injuries.

The HCE-2 cell line was used as a model for corneal cells. The effective concentrations of 2-chloroethyl ethyl sulfide (CEES) – as an analog of SM – doxycycline, and curcumin were determined using the MTT assay. The gene expression of MMP-2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP-1) was evaluated by the real-time PCR method. Also, the activity of MMP-2 and MMP-9 enzymes was determined by zymography.

The expression of the MMP-2 and MMP-9 genes increased 5- and 3.3-fold after exposure to CEES, respectively. Following the treatment with curcumin and doxycycline, MMP- 2 expression decreased significantly. Also, after treatment with curcumin and doxycycline, the MMP-9 expression decreased 2.5- and 1.6-fold, respectively. The reduction in activity was 32% for MMP-2 and 56% for MMP-9 after treatment with curcumin. The corresponding values were 12% and 40% following doxycycline treatment. There was no significant difference between the effects of curcumin and doxycycline on reducing MMP-2 expression, but the difference was statistically significant in the case of MMP-9.

Doxycycline and curcumin can inhibit MMP expression and activity in chemically exposed corneal cells. Curcumin has a greater ability than doxycycline to inhibit MMP-2 and MMP- 9 enzymes; however, the difference is statistically significant only in the case of MMP-9. After further validation, these substances can be introduced as anti- inflammatory agents to treat corneal chemical burns.

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.

 Highly metastatic breast cancer is a population of cancer cells that has metastasized to other organs in the body leading to apoptosis resistance. It was reported that MDAMB-231 cells contain lower levels of reactive oxygen species associated with metastatic capability. Curcuma longa (CL) possesses cytotoxic effects in several cancer cells including metastatic breast cancer cells. This study aimed to investigate the effect of CL-inhibited cell migration in highly metastatic breast cancer MDAMB-231 cells.

Experimental approach: 

CL was extracted under maceration with methanol. The cytotoxic effect on single and combination treatment of CL was assessed through the MTT assay. Migration analysis was evaluated using scratch wound healing assay, MMP-9 expression by gelatine zymography, Rac-1, and MMP-9 gene expression using Real-Time Quantitative Reverse transcription polymerase chain reaction (qRT-PCR). The apoptosis induction was analyzed through Bax gene expression and Bcl-2 protein expression.

 We found that CL inhibits the growth of MDAMB-231 cells, induces Bax gene expression, and suppresses Bcl-2 expression in a dose-dependent manner. Moreover, cancer cell migration was suppressed by the presence of CL. qRT-PCR and gelatine zymography assay showed that CL downregulates Rac-1 and MMP-9 gene expression.

Conclusion and implications:

 CL could inhibit the growth and migration of highly metastatic breast cancer cells by reducing the Rac-1 gene expression and regulating apoptosis protein expression.

Oral lichen planus (OLP) is a chronic mucocutaneous disease, involving the skin and mucous membranes. Although the pathogenesis of OLP is not fully understood, the immune system, genetic and environmental factors, medications, and infections may play an important role in OLP. The level of matrix metalloproteinases (MMPs) is known to increase in pathological conditions, such as squamous cell carcinoma (SCC), as well as inflammatory conditions, such as OLP. If pain and soreness are present, topical corticosteroids (CSs) are the first-line treatment for these patients. This study aimed to evaluate the level of MMP-9 in individuals with OLP before and after treatment with triamcinolone 0.2% mouthwash.

This study was conducted on 18 patients with erosive-atrophic OLP. First, 5 mL of unstimulated saliva was collected, and then, triamcinolone 0.2% mouthwash was prescribed to all the patients. After treatment and healing of the lesions, a sample was collected again from the participants. The MMP-9 concentration was quantified in all the samples using an ELISA kit.

The mean age of the participants, including five males and 13 females, was 45.7 years in this study. Before treatment, the mean MMP-9 concentration was 1.599 ng/mL, with a standard deviation (SD) of 1.074, while the mean (±SD) level of MMP-9 was 0.933 ng/mL (0.649) after treatment. The mean reduction was estimated at 0.666, with SD of 1.056 (P=0.016).

The MMP-9 level was significantly lower after treatment compared to the pretreatment stage. Based on the results, topical CSs, such as triamcinolone, can decrease the level of MMP-9, as a reliable biomarker of OLP severity; therefore, they can diminish inflammation and prevent the dysplastic progression of the disease.

The expression of matrix metalloproteinase-9 (MMP-9) and chemokine receptor 7 (CCR7) is significantly associated with tumor invasion and metastasis. Little is known regarding the potential of these markers in predicting cancer metastasis in Laryngeal Squamous Cell Carcinoma (LSCC). Therefore, this study aimed to dissect the potential of these markers in predicting the lymph node metastasis in LSCC patients.

Sixty tissue samples were obtained from the patients diagnosed pathologically with LSCC who underwent partial or total laryngectomy. The expression of MMP-9 and CCR7 was measured using the immunohistochemistry staining in the tissue samples of LSCC patients. The ROC (receiver operating characteristic) curve was used to determine the most significant cut-off points of expression according to the highest sensitivity and specificity of both the markers to predict the lymph node metastasis in LSCC. Then, the relationship between the clinicopathology features and the expression of MMP-9 and CCR7 was evaluated.

The expression of both MMP-9 and CCR7 was significantly correlated with the lymph node metastasis in LSCC (P<0.001). Furthermore, CCR7 expression exhibited the highest prediction accuracy (AUC 95.7%) and sensitivity (100%) in predicting the lymph node metastasis in LSCC compared to that of MMP-9 (AUC 92.9%, sensitivity 90%). We also found that patients with larger tumor size (> 4 cm) had significantly higher expression of MMP-9 and CCR7 (P<0.002 and P<0.001, respectively). The Elevated expression level of CCR7 statistically correlated with higher MMP-9 expression (P<0.001).

MMP-9 and CCR7 might be beneficial as predictors of lymph node metastasis in LSCC patients.

Prostate cancer is the second cause of death among men. Nowadays, treating various cancers with medicinal plants is more common than other therapeutic agents due to their minor side effects. This study aimed to evaluate the effect of taraxasterol on the prostate cancer cell line.

Experimental approach:

 The prostate cancer cell line (PC3) was cultured in a nutrient medium. MTT method and trypan blue staining were used to evaluate the viability of cells in the presence of different concentrations of taraxasterol, and IC50 was calculated. Real-time PCR was used to measure the expression of MMP-9, MMP-2, uPA, uPAR, TIMP-2, and TIMP-1 genes. Gelatin zymography was used to determine MMP-9 and MMP-2 enzyme activity levels. Finally, the effect of taraxasterol on cell invasion, migration, and adhesion was investigated.

Taraxasterol decreased the survival rate of PC3 cells at IC50 time-dependently (24, 48, and 72 h). Taraxasterol reduced the percentage of PC3 cell adhesion, invasion, and migration by 74, 56, and 76 percent, respectively. Real-time PCR results revealed that uPA, uPAR, MMP-9, and MMP-2 gene expressions decreased in the taraxasterol-treated groups, but TIMP-2 and TIMP-1 gene expressions increased significantly. Also, a significant decrease in the level of MMP-9 and MMP-2 enzymes was observed in the PC3 cell line treated with taraxasterol.

Conclusion and implications:

 The present study confirmed the therapeutic role of taraxasterol in preventing prostate cancer cell metastasis in the in-vitro study.

Sandoricum koetjape has been used for generations in traditional Indonesian medicine. The leaves were used to treat helminthiasis, cough, stomachache, diarrhea, bloating, leucorrhoea, colic, and fever in Indonesia. Identification of phenolic acids in the Sandoricum koetjape leaves was done by ultrahigh-pressure liquid chromatography (UPLC). Gallic acid, 4-hydroxybenzoic acid, chlorogenic acid, caffeic acid, syringic acid, p-coumaric acid, and ferulic acid were identified as phenolic acids found in Sandoricum koetjape leaf extracts. Heart disease, stroke, and cancer are the three noncommunicable diseases that kill the most people in Indonesia. Coronary artery disease, cardiovascular disease, cardiomyopathy, cancer, tumor, type 2 diabetes, and cholesterol have all been linked to MMP-9. This study aimed to determine the phenolic acids contained in the leaves of Sandoricum koetjape and to determine their inhibitory activity against the matrix metalloproteinase-9 (MMP-9). Molecular docking studies were carried out by the autodock 4.2 program integrated with the pyrx v.09.8 virtual screening tool. The chlorogenic acid in Sandoricum koetjape leaf extract binds more strongly than the other phenolic acids. Interacting between chlorogenic acid with MMP-9 on amino LEU187, LEU188, ALA189, HIS405, and TYR423. AdmetSAR and Protox II databases were used for physiochemical and ADMET properties. Chlorogenic acid is expected to have high oral bioavailability in humans, good intestinal absorption, and an equivalent distribution in the intestine and blood plasma. Chlorogenic acid’s acute toxicity is also expected to be low. Chlorogenic acid is also non-toxic to the liver, immune system, mutagenic, and cytotoxic. Sandoricum koetjape phenolic acid, particularly chlorogenic acid, appeared to be an efficient MMP-9 inhibitor based on docking results.

Smoking has been extensively investigated in oncology, and controversial associations with brain tumor incidence have been reported. Caspase-3 and matrix metalloproteinases (MMPs) belong to an important cascade in tumor vasculogenesis. We aim to study the smoking impact on these signaling molecules in nontumoral rat brain tissue.

Methods and Materials/Patients: 

A total of 60 Wistar rats were divided into two groups: treatment (cigarette smoke/electronic cigarette) and control groups with subgroups of male and female rats. After general anesthesia and decapitation, their brains were collected, and 3-μm thick coronal sections were prepared. Following immunohistochemical staining with rabbit anti-MMP-2 and anti-caspase-3 antigens, protein expressions were analyzed by selecting two fields at 400x magnification.

Our data suggest that the expression of MMP-2 was not significantly different between the studied groups. However, the significant inductive activity of cigarette smoking was observed on caspase-3.

Cigarette smoking indicates pro-tumoral signaling impact in normal tissue with activation of caspase-3 in rat brain tissue.

It has been reported that less than 5% of women experience recurrent pregnancy loss (RPL). different matrix metalloproteinases (MMPs) have proteolysis function with a main role in the stable development of the fetus.

This study aims to assess the associations between two single nucleotide polymorphisms (rs2509013 C>T and rs11225395 G>A) of MMP-8 gene and RPL among 130 Iranian women with a history of RPL and 130 controls.

Genotyping of the MMP-8 gene was done for the two polymorphisms by using Sanger sequencing method.

High frequency of AA genotype (OR: 2.5, 95%CI:1.02-4.1, P<0.01) and A allele (OR:1.95, 95% CI:0.95-3.1, P<0.001) of rs11225395 G>A polymorphism in patients compared to controls. This high frequency was also reported in the haplotypes and combined genotypes of polymorphism.

The MMP-8 gene may be involved in RPL risk and is a potential biomarker for RPL susceptibility.

To investigate the clinical efficacy and safety of docetaxel in combination with cisplatin in comparison of standard methods of in treatment of platin-sensitive ovarian cancer regimens and in addition to radiotherapy for whole abdomen radiotherapy in platin-sensitive recurrent ovarian cancer and the effect on the levels of VEGF and MMP-2.

We recruited a total of 160 platin-sensitive recurrent ovarian cancer patients between April 2017 and April 2020 who were treated in this hospital, and assessed them based on the treatment chemotherapy and radiotherapy regimens to control, the docetaxel+cisplatin, and Whole abdomen radiotherapy groups. Patients in the control group received the co-medication of paclitaxel and carboplatin, while those in the docetaxel+cisplatin group received the docetaxel in combination with cisplatin. Following treatment, we compared the clinical efficacy, levels of vascular endothelial growth factor (VEGF) and MMP-2 and safety of these three methods between two groups.

the total effectiveness rate of the docetaxel+cisplatin group was 69.09%, significantly higher than 16.36% in the control group and 24% in WAR group (P<0.05). Besides, it was found that treatment in the docetaxel+cisplatin group decreased the levels of VEGF and MMP-2 in serum of patients more evidently than those in the control and whole abdomen radiotherapy groups (P<0.05).

docetaxel in combination with cisplatin performs well, with significant decreases in the levels of VEGF and MMP-2 and reliable safety; while there was a high rate of adverse reactions in patients undergoing whole abdomen radiotherapy.

We aimed to evaluate the impact of the tryptanthrin (TRP) compound, with antimicrobial and anti-inflammatory effects, on the excisional wound (EW) model. In an EW model in mice, we tried to explain the possible effect of TRP through vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) that contribute significantly to wound healing.

A total of 90 BALB-C female mice aged 6 - 8 weeks were used in the present study. Animals were randomly divided into five groups. After creating the EW model, three different doses (1, 2.5, 5 mg/kg) of TRP compound were applied topically for 14 days, and wound closure rates were measured on days 0, 3, and 7. Vascular endothelial growth factor and MMP-9 were evaluated on days 3, 7, and 14 on wound explants and on day 14 on serum samples by enzyme-linked immunosorbent assay. Histopathological analysis was performed on wound explants.

After the EW model creation, significant healing of the wound areas was observed in the groups for which TRP was applied, especially on the third day. Moreover, in groups that received the third dose of TRP, the wound closure rate was 94%. It was found that the wound areas were closed due to the increase in TRP dose. In line with wound healing, VEGF and MMP-9 levels gradually rose on the third and seventh days and decreased on the 14th day.

Tryptanthrin compound usage on the EW model increased wound healing and did not leave a scar after 14 days.

Diabetes is a metabolic disease and is associated with failure of various organs. Macrophage migration factor (MIF) and matrix metalloproteinase (MMP-9) are two of the most important factors in the pathogenesis of diabetes.

In this descriptive-analytical study, 30 patients with type 2 diabetes mellitus from Hamadan Diabetes Center were selected by convenience sampling. Moreover, 30 healthy first-degree relatives and 30 unrelated non-diabetics, were examined for MMF and MMP-9 and their variations based on age, gender, body mass index (BMI) and hemoglobin A1C.

The mean and standard deviation of MIF in diabetic patients, and relatives and non-relatives of diabetic patients were 592.87±78.19, 131.82±88.27 and 94.63±23.88, respectively (P<0.001). The mean and standard deviation of the MMP-9 in diabetic patients, and relatives and non-relatives of diabetic patients were 2570.64±2220.03, 918.57±650.08 and 629.09±288.32, respectively (P<0.001). MIF and MMP-9 did not have a significant relationship with age, sex, duration of disease and BMI. However, we observed a direct and significant correlation between hemoglobin A1C and the level of MIF and MMP-9 (P<0.001). In patients with type 2 diabetes, serum levels of MMP-9 and MIF, consistent with HbA1c, increase with no significant association with age, sex, BMI and duration of diabetes.

Matrix metalloproteinase-13 (MMP-13) is a proteolytic enzyme playing an important role in the activation of the MMP cascade, which seems to be vital in both bone metabolism and homeostasis. However, the up-regulation of MMP-13 is involved in developing several human disorders such as aggressive tumors, tooth decay, rheumatoid arthritis, osteoarthritis, skin ageing, and Alzheimer's disease. We performed a molecular docking analysis to discover the potential MMP-13 inhibitors in a total of 21 anthraquinone derivatives. The binding affinity of the tested compounds to the MMP-13 catalytic site was estimated by the Autodock 4.0 software. Moreover, the stability of the docked pose of the top-ranked compounds were examined using molecular dynamics simulations. Pulmatin, sennidin A, emodin-8-glucoside, emodin, rhodoptilometrin, chrysophanol, knipholone, sennidin B, aloe emodin 8-glucoside, and aloe-emodin demonstrated considerable binding affinity to the MMP-13 active site. However, the molecular dynamics simulations showed that the docked poses of sennidin A and sennidin B were not considerably stable. The present study suggested that pulmatin, emodin-8-glucoside, emodin, rhodoptilometrin, chrysophanol, knipholone, aloe emodin 8-glucoside, and aloe-emodin may be considered as drug candidates for therapeutic applications in many human diseases. However, the validation of this finding is needed in the future.

Finding a sample of healthy tissue is a critical challenge in research studies. Non-pathological Tissue adjacent to the tumor (NAT) specimens is usually used as the control in several studies. However, little is known about the similarity of NAT to healthy tissues. Here, we compared the expression of Matrix Metalloproteinase 2 (MMP-2) and its inhibitor, Tissue Inhibitors of MMP (TIMP)-1 as extracellular matrix remodeling factors in NAT and autopsy lung tissue. RNA of 7 NAT and 6 Formalin-Fixed Paraffin-Embedded (FFPE) lung autopsies from healthy people as the control group was extracted, and cDNA was synthesized. The gene expression levels of MMP-2 and TIMP-1 were evaluated by real-time PCR. There were no significant differences in the expression of MMP-2, TIMP-1, or their ratio between the two groups. The results showed that NAT could be used as healthy controls in lung tissue studies for MMP-2 and TIMP-1.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinase. Several studies have reported the association between the single nucleotide polymorphisms(C/T) -1562 in the MMP-9 promoter and the risk of cancer. In this study, we decided to carry out a comprehensive meta-analysis to obtain a reasonable result about the association between this polymorphism and the risk of lung cancer.

A complete literature review was conducted within the databases of ISI Web of Knowledge, google scholar, and PubMed for studies on lung cancer published from 2002 to 2018. A meta-analysis was conducted which included more than 3000 case and control subjects. The pooled Odds Ratio (OR) and 95% Confidence Intervals ( CI) were used for dominant, recessive, and co-dominant MMP-9 genotypes to assess the strength of the association.

Analysis indicated no significant association between MMP-9-1562C/T polymorphism and the risk of lung cancer, dominant model; [CT+TT/CC]: OR = 0.972, 95% CI = 0.811–1.164, recessive model [CC+CT/TT] OR= 1.027, 95% CI = 0.651–1.618 and co-dominant model [TT/CC] OR = 0.983, 95% CI = 0.550–1.755.

No association was observed between the MMP9 -1562 C/T polymorphism and the incidence of lung cancer. The meta-analysis demonstrated that this polymorphism can't serve as a diagnostic marker for lung cancer.