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1.
Pathol Res Pract ; 257: 155286, 2024 May.
Article in English | MEDLINE | ID: mdl-38599044

ABSTRACT

In spite of the decrease in breast cancer (BC) death rates, it has remained a significant public health concern. Dysregulation of the Hippo pathway contributes to breast cancer development and progression by enhancing cancerous cell proliferation, survival, invasion, and migration. Investigating the connection between specific lncRNAs (SNHG15, HCP5, and LINC01433) and YAP and WWTR1, and the impact of these lncRNAs on the expression of YAP and WWTR1 proteins in the Hippo pathway, may offer valuable understanding for BC diagnosis and treatment. Forty BC tissue samples were acquired from the Tumor Bank and utilized for RNA and protein extraction. Real-time PCR and western blotting techniques were performed to assess the gene and protein expressions, respectively. Correlations between variables and their associations with clinicopathological features in BC were evaluated using Mann-Whitney U or Student's t-test. Additionally, the analysis of the GEO database was utilized to validate the findings. In cancerous tissue, the up-regulation of YAP, WWTR1, HCP5, SNHG15, and Linc01433 at both the mRNA and protein levels corresponds to the findings in GEO datasets. A significant association was found between YAP and histological grade, while WWTR1 showed a correlation with family history and HER-2. The distinct and notable expression of YAP, WWTR1, SNHG15, HCP5, and Linc01433 in BC tissues, together with the results of combined ROC curve analysis derived from our finding and GEO database suggest that a combined panel of these 5 RNAs may have great potential in predicting of BC and its management.


Subject(s)
Adaptor Proteins, Signal Transducing , Breast Neoplasms , Gene Expression Regulation, Neoplastic , RNA, Long Noncoding , Transcription Factors , Transcriptional Coactivator with PDZ-Binding Motif Proteins , YAP-Signaling Proteins , Female , Humans , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/genetics , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , RNA, Long Noncoding/genetics , Trans-Activators/genetics , Transcription Factors/genetics , YAP-Signaling Proteins/genetics , YAP-Signaling Proteins/metabolism
2.
Chonnam Med J ; 60(1): 59-68, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38304125

ABSTRACT

Contrast-induced acute kidney injury (CI-AKI) is a frequent challenge following the injection of contrast media and its subsequent oxidative stress. The aim of the present study was to evaluate the preventive effects of coenzyme Q10 (Q10), as a mitochondrial-targeted antioxidant in CI-AKI in diabetic patients, who account for a large proportion of angiographic cases. A total of 118 diabetic patients were randomly assigned to receive 120 mg of oral coenzyme Q10 (Q10 group) or placebo (Placebo group) for four days, starting 24 hours before contrast media injection. Blood urea nitrogen (BUN), serum and urinary creatinine, estimated glomerular filtration rate (eGFR), urinary malondialdehyde (UMDA), urinary total antioxidant capacity (UTAC), and urinary mitochondrial to nuclearDNA ratios (mtDNA/nDNA ratio) were evaluated before and after the treatment period. Urine sediments were also evaluated to report the urine microscopy score (UMS).The levels of BUN, serum and urine creatinine, and UMS were similar in the Q10 and placebo groups. EGFR was lower in the Q10 group before the treatment (p=0.013) but not after. The urinary mtDNA/nDNA ratio was 3.05±1.68 and 3.69±2.58 in placebo and Q10 groups, but UTAC was found to be lower in Q10 both before (p=0.006) and after the treatment (p<0.001). The incidence of CI-AKI was 14.40% and the mtDNA/nNDA ratio was similar between CI-AKI and non-CI-AKI patients. In conclusion, Q10 treatment shows no favorable effect on prevention of CI-AKI or a urinary mtDNA/nDNA ratio among diabetic patients.

3.
Int J Biol Macromol ; 258(Pt 2): 129048, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38159701

ABSTRACT

Lysine Specific Demethylase 1 (LSD1) has been identified as a chromatin-modifying enzyme implicated in various cancer pathogeneses, highlighting the potential for novel epigenetic cancer treatments through the development of effective inhibitors. We employed 3D-QSAR pharmacophore modeling, molecular docking, and molecular dynamics simulations to identify a promising drug candidate for LSD1 inhibition. RMSD, RMSF, H-bond, and DSSP analysis demonstrated that ZINC02599970 (Arformoterol) and ZINC13453966 exhibited the highest LSD1 inhibitory potential. Experimental validation using MCF-7 and MDA-MB-231 cell lines revealed that Arformoterol displayed potent antiproliferative activity with IC50 values of 12.30 ± 1.48 µM and 19.69 ± 1.15 µM respectively. In contrast, the IC50 values obtained for the control (tranylcypromine) in exposure to MCF-7 and MDA-MB-231 cells were 104.6 ± 1.69 µM and 77 ± 0.67 µM, respectively. Arformoterol demonstrated greater LSD1 inhibitory potency in MCF-7 cells compared to MDA-MB-231 cells. Also, the expression of genes involved in chromatin rearrangement (LSD1), angiogenesis (VEGF1), cell migration (RORα), signal transduction (S100A8), apoptosis, and cell cycle (p53) were investigated. Arformoterol enhanced apoptosis and induced cell cycle arrest at the G2/M phase, both in MCF-7 and MDA-MB-231 cancer cells. Based on our findings, we propose that Arformoterol represents a promising candidate for breast cancer treatment, owing to its potent LSD1 inhibitory activity.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Humans , Female , Molecular Dynamics Simulation , Molecular Docking Simulation , Breast Neoplasms/drug therapy , Quantitative Structure-Activity Relationship , Pharmacophore , Histone Demethylases , Chromatin , Enzyme Inhibitors/pharmacology , Cell Proliferation , Antineoplastic Agents/pharmacology
4.
J Assist Reprod Genet ; 40(2): 343-359, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36593322

ABSTRACT

PURPOSE: We hypothesized that immature oocytes are associated with impaired energy production in surrounding granulosa cells (GCs) in polycystic ovary syndrome (PCOS). Thus, this study investigated mitochondrial function, determined expression of glycolytic regulatory enzymes, and measured ATP levels in GCs of PCOS patients. METHODS: GCs were isolated from forty-five PCOS patients and 45 control women. Intracellular concentration of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), the rate of glycolysis, total antioxidant capacity (TAC), activities of catalase (CAT) and superoxide dismutase (SOD), and ATP level were measured in GCs. The gene expression and protein levels of glycolytic enzymes (hexokinase, muscular phosphofructokinase, platelet derived phosphofructokinase, and muscular pyruvate kinase) were determined. Association of GC energy level with oocyte maturation was further validated by measuring glycolysis rate and ATP level in GCs isolated from mature and immature follicles from new set of fifteen PCOS patients and 15 controls. RESULTS: PCOS patients showed higher ROS level, decreased TAC, reduced CAT and SOD activities, and lower Δψm together with reduced expression of key glycolytic enzymes. ATP concentration and biochemical pregnancy were lower in PCOS compared with control group. ATP levels were found to be significantly correlated with ROS and Δψm (r = - 0.624 and r = 0.487, respectively). GCs isolated from immature follicles had significantly lower ATP levels and rate of glycolysis compared with the GCs separated from mature follicles in both PCOS patients and control. CONCLUSION: Declined energy due to the mitochondrial dysfunction and restrained glycolysis in GCs is associated with the immature oocytes and lower biochemical pregnancy in PCOS.


Subject(s)
Polycystic Ovary Syndrome , Pregnancy , Humans , Female , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , Reactive Oxygen Species/metabolism , Granulosa Cells/metabolism , Antioxidants/metabolism , Phosphofructokinases/genetics , Phosphofructokinases/metabolism , Adenosine Triphosphate/metabolism
5.
Cancer Invest ; 41(1): 58-69, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36282109

ABSTRACT

Bladder cancer as one of the main comorbid diseases might be more susceptible to develop COVID-19 infection with a higher mortality risk during the COVID-19 pandemic. The European Association of Urology (EAU) recommended a comprehensive panel for bladder cancer diagnosis and treatment during this global health problem. The urgent need for treatments of COVID-19 during the pandemic has persuaded researchers to evaluate the different medications, which may lead to drug shortages. Therefore, in this review paper, we have focused on the least recommendations of EAU about bladder cancer during of COVID-19 pandemic to provide a comprehensive panel for high-risk patients.


Subject(s)
COVID-19 , Urinary Bladder Neoplasms , Humans , Delivery of Health Care , Neoplasm Invasiveness , Pandemics , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/therapy
6.
Int J Reprod Biomed ; 20(4): 299-306, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35822186

ABSTRACT

Background: Methylenetetrahydrofolate reductase enzyme (MTHFR) plays a key role in regulating folate balance, converting homocysteine to methionine, and producing s-adenosylmethionine (SAM) that plays a role in the methylation process. Objective: This study aimed to determine MTHFR activity and SAM level in men with normozoospermia and oligozoospermia. Materials and Methods: 30 oligozoospermic and 30 normozoospermic men as controls were enrolled in this case-control study. Semen analysis was conducted according to the world health organization criteria. All semen samples were collected after 3-5 days of sexual abstinence. The sperms were evaluated by sperm test video software. All subjects SAM level was measured by enzyme-linked immunosorbent assay kit, and MTHFR were measured manually. Results: 2 groups had a significant difference in sperm morphology (p = 0.02), concentration (p = 0.02) and motility (p = 0.03). The MTHFR activity in normozoospermic and oligozoospermic groups had significantly differences (p = 0.01). The level of SAM in the semen of oligozoospermic men was statistically lower than normozoospermic men (p = 0.03). Also, there was a positive association between MTHFR enzyme activity and SAM level in the normozoospermia group (p = 0.02, ß = 0.67) and oligozoospermia group (p = 0.03, ß = 0.54). Conclusion: MTHFR activity and SAM concentration were statistically lower in oligozoospermia men. It seems they can affect sperm concentration, morphology, and motility.

7.
Andrologia ; 54(1): e14258, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34609765

ABSTRACT

Low motility is one of the causes of male infertility. In this study, the effects of progesterone solid lipid nanoparticles (SLNs) on sperm capacitation, acrosome reaction, oxidative stress and expression of SPACA1 and MAPK way genes were investigated. Progesterone SLNs were synthesized using the solvent emulsification evaporation method. Twenty asthenozoospermia samples were selected, and sperm and acrosome membrane integrity, acrosome reaction, sperm motility, viability, total antioxidant capacity (TAC), total oxidative status tests and PKA, PTK, P38MAPK and SPACA1 gene expressions were assessed. The synthesized nanoparticles were prepared with the size (187.6 nm), PDI (0.184), EE (85.82%), LP (3.43%) and ZP (-23.5mV). Progesterone SLNs increased sperm and acrosome membrane integrity and TAC (p < .05). Also, the expression of P38MAPK, PKA, PTK, and SPACA1 genes in this group showed a significant increase (p < .001). Progesterone SLNs increased acrosome reaction, sperm capacitation and TAC. Also, it increased the expression of PTK PKA, SPACA1 and P38MAPK genes.


Subject(s)
Asthenozoospermia , Nanoparticles , Acrosome , Acrosome Reaction , Asthenozoospermia/drug therapy , Asthenozoospermia/genetics , Humans , Liposomes , Male , Progesterone/pharmacology , Sperm Capacitation , Sperm Motility , Spermatozoa
8.
Clin Lab ; 67(11)2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34758223

ABSTRACT

BACKGROUND: Cirrhosis is often an asymptomatic disease. Its early diagnosis before the development of life-threatening complications is an important step to prevent the progression of the disease. The aim of the present study was the identification of parameters that are significantly changed in cirrhosis, are not affected by the cause of cirrhosis, and are associated with fatal complications of cirrhosis. METHODS: Demographic and pre-transplant ultrasound and laboratory findings were reviewed in patients with viral- (n = 27), autoimmune hepatitis- (n = 27), alcohol- (n = 18), primary sclerosing cholangitis- (PSC) (n = 36), and nonalcoholic steatohepatitis-related cirrhosis (n = 42). RESULTS: Among laboratory findings, only the aspartate aminotransferase-to-platelet ratio index (APRI) value in cirrhotic patients was significantly higher than that of healthy individuals (p < 0.001) and, meanwhile, its value was not different among cirrhotic patients with various etiologies (p = 0.240) but was associated with the ascites, as a cirrhosis life-threatening complication (p < 0.001). CONCLUSIONS: The APRI has acceptable potential to predict prognosis in cirrhosis. So, it can be a possible parameter to the prediction of the lethal complications of cirrhosis.


Subject(s)
Liver Cirrhosis , Aspartate Aminotransferases , Humans , Liver Cirrhosis/diagnosis , Platelet Count , Prognosis , ROC Curve , Retrospective Studies , Ultrasonography
9.
Metabol Open ; 11: 100122, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34514363

ABSTRACT

As of August 5, 2021, there were about 200,000,000 global confirmed patients of COVID-19, with more than 4,250,000 deaths. The COVID-19 disease which is a tremendous public health threat, jumps unpredictably and outbreaks very quickly. The overall mortality rate of COVID-19 infection is 1%-15% but reaches up to 17-38% in older cases with chronic disorders and in intensive care unit (ICU) subjects. Diabetic patients, particularly those whose disease is not well controlled can be more susceptible to COVID-19. Although diabetes was present in 5.3%-42.3% of fatalities from COVID-19, the underlying pathophysiological mechanisms of action of novel coronavirus in diabetic patients are unknown. Based on the elevating of global prevalence, diabetes is the main medical problem associated with COVID-19. It is plausible that diabetes can forecast elevated severity of pneumonia. The mortality of lung infection among diabetes is remarkably higher compared with non-diabetic patients. Mechanisms responsible for severe pneumonia in the diabetic patients as well as treatment of diabetic patients infected with COVID-19 are largely speculative. Hence, this paper will summarize the recent findings related to the mechanisms of pneumonia and treatment strategies in diabetic patients.

10.
Mol Biol Rep ; 48(5): 4253-4262, 2021 May.
Article in English | MEDLINE | ID: mdl-34086159

ABSTRACT

Cells translate the mechanosensing of extracellular matrix component dysregulation and stiffness into the signal transduction including Osteopontin (OPN) through the Hippo pathway. But how extracellular matrix (ECM) component dysregulation and stiffness are ultimately linked to transitional cell carcinoma (TCC) development remains poorly understood. This study was aimed to evaluate the possible links between ECM component alteration after cancer surgery and OPN and Yes-associated protein (YAP) expression in TCC and adjacent tissues. In this study, we used 50 TCC (25 newly diagnosed and 25 recurrent) and 50 adjacent tissues to determine the tissue stiffness using atomic force microscopy. The mRNA expression of SPP1, Indian hedgehog (IHH), and YAP was also determined using qRT-PCR. Western blotting and ELISA were performed to assess the tissue and serum levels of OPN, respectively. To assess the glycoproteins and elastic fibers content, Periodic Acid Schiff, and Verhoeff-Van Gieson Staining were performed, respectively. Matrix stiffness was markedly higher in TCCs than adjacent tissues (p < 0.05). Gene expression analysis showed that YAP, SPP1, and IHH genes were upregulated in TCC tissues (p < 0.05). Additionally, the OPN protein overexpression was observed in the tissue and the serum of TCC patients (p < 0.05). We also found that glycoproteins, elastic fibers content of recurrent TCC tissues was remarkably higher as compared to adjacent tissues (p < 0.05). Our results suggest that glycoproteins and elastic fibers content modulation and ECM stiffness may upregulates the expression of YAP, SPP1 and IHH genes, and possibly contribute to the TCC development and relapse.


Subject(s)
Carcinoma, Transitional Cell/genetics , Extracellular Matrix/metabolism , Gene Expression Regulation, Neoplastic , Neoplasm Recurrence, Local/genetics , Osteopontin/genetics , Urinary Bladder Neoplasms/genetics , YAP-Signaling Proteins/genetics , Aged , Carcinoma, Transitional Cell/blood , Case-Control Studies , Elastin/metabolism , Female , Gene Expression , Hedgehog Proteins/genetics , Hippo Signaling Pathway/genetics , Humans , Male , Neoplasm Recurrence, Local/blood , Osteopontin/blood , Proteoglycans/metabolism , Up-Regulation/genetics , Urinary Bladder Neoplasms/blood
11.
J Proteomics ; 240: 104208, 2021 05 30.
Article in English | MEDLINE | ID: mdl-33785428

ABSTRACT

Although antibody mediated rejection (AMR) accounts for 20-30% of all acute renal allograft rejections, introducing biomarkers for a timely detection of allograft rejection has been remained challenging. This study investigated novel diagnostic biomarkers of AMR by examining of urine proteome in renal transplant patients. Thirty-six patients with kidney transplantation including 22 AMR patients and 14 patients with stable renal function (control group) were enrolled in this study. Urinary samples were collected and Label free quantification (LFQ) proteomics technique was applied on urine samples and data was subjected to Random Forest (RF) algorithm to predict main candidate proteins contributing in AMR. Finally, applicability of candidate diagnostic biomarkers was evaluated in new sets of AMR subjects, stable patients and healthy volunteers. A total of 1020 proteins were detected in urine proteome. RF algorithm predicted 20 differentially expressed proteins with the highest sensitivity and specificity and combination of EGF, COL6A, and NID-1 was identified as possible panel for early diagnosis of AMR. Applicability of EGF as diagnostic biomarker was validated in urine samples of independent set of AMR subjects. This is the first urinary proteomics study in AMR patients demonstrating that urinary EGF might be used as early diagnostic biomarker for AMR. SIGNIFICANCE: Renal antibody mediated rejection (AMR) accounts for 20-30% of all acute rejections of allografted kidneys. Although several possible biomarkers have been proposed to predict AMR, ineffectiveness of current urinary biomarkers in early diagnosing of AMR patients and in distinguishing AMR subjects from patients with stable kidney function casts doubts on their applicability in clinic. Here for the first time and based on the analysis of urinary proteome we showed that uEGF and uEGF/Cr might be candidate biomarkers to predict AMR with high diagnostic power.


Subject(s)
Epidermal Growth Factor , Kidney Transplantation , Allografts , Biomarkers , Early Diagnosis , Graft Rejection/diagnosis , Humans , Kidney , Proteomics
12.
Indian J Clin Biochem ; 35(4): 458-464, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33013016

ABSTRACT

In the current study, we aimed to investigate the effect of carvacrol on the suppression of liver fibrosis progression through targeting lysyl oxidase (LOX) expression. The rats received carbon tetrachloride (CCl4) intraperitoneally and carvacrol orally for 10 weeks. Liver damage was evaluated by measuring the serum level of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and hepatic oxidative stress parameters including total antioxidant capacity, total thiol group and total oxidant status spectrophotometry and malondialdehyde fluorometrically. Extracellular deposition of collagen was detected using Masson's trichrome standing. Furthermore the gene expression of lysyl oxidase homolog 2 (Loxl2) was analyzed using quantitative reverse transcription-polymerase chain reaction. And then the protein level of LOX was detected in liver tissue by western blot method. Carvacrol administration normalized serum biochemical parameters and improved oxidative stress status in liver homogenate of CCl4 treated rats. Collagen fiber bundles in interlobular spaces were decreased remarkably by carvacrol treatment. Also, carvacrol downregulated hepatic gene expression of Loxl2 and protein level of LOX. Our data clearly revealed that carvacrol suppresses progression of liver fibrosis development via attenuating of liver damage and oxidative stress status as well as via downregulation of hepatic gene expression of Loxl2 and protein level of LOX.

13.
Ann N Y Acad Sci ; 1473(1): 48-61, 2020 08.
Article in English | MEDLINE | ID: mdl-32428277

ABSTRACT

Changes in the cellular microenvironment play a critical role in the development of bladder cancer (BC). Yes-associated protein (YAP), a central mediator of the Hippo pathway, functions as a nuclear sensor of mechanotransduction that can be induced by stiffness of the extracellular matrix (ECM), including stiffness resulting from surgical manipulations. We aimed to clarify the possible association between surgically-related ECM stiffness and YAP activation in BC patients. We compared 30 bladder cancer tissues with grade II (n = 15 recurrent and n = 15 newly diagnosed) with 30 adjacent healthy tissues. Atomic force microscopy showed that patients with recurrent BC had stiffer ECM than newly diagnosed patients (P < 0.05). Gene expression profiles showed that ß1 integrin (ITGB1), focal adhesion kinase (FAK), CDC42, and YAP were upregulated in cancerous tissues (P < 0.05); additionally, ß1 integrin activation was confirmed using a specific antibody. Nuclear localization of YAP was higher in recurrent cancerous tissues compared with newly diagnosed and it was positively associated with higher stiffness (P < 0.05). Our results suggest that postsurgery-induced ECM stiffness can influence integrin-FAK-YAP activity and thereby YAP trafficking to the nucleus where it contributes to BC progression and relapse.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Biomarkers, Tumor/metabolism , Mechanotransduction, Cellular/physiology , Transcription Factors/metabolism , Tumor Microenvironment/physiology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/surgery , Adaptor Proteins, Signal Transducing/chemistry , Aged , Biomarkers, Tumor/chemistry , Extracellular Matrix/metabolism , Extracellular Matrix/pathology , Female , Humans , Male , Middle Aged , Protein Structure, Secondary , Protein Structure, Tertiary , Transcription Factors/chemistry , Urinary Bladder Neoplasms/pathology , YAP-Signaling Proteins
14.
Ann N Y Acad Sci ; 1465(1): 117-131, 2020 04.
Article in English | MEDLINE | ID: mdl-31696937

ABSTRACT

The pivotal role of the extracellular matrix (ECM) as both a cause and consequence of liver fibrosis is striking. However, mechanotransducer molecules and profibrogenic factors induced by liver stiffness are still unclear. The current study aimed to investigate liver stiffness and its correlation with the expression of the transcriptional coactivator with PDZ-binding motif (TAZ) and serum osteopontin (OPN) in human cirrhosis. In this case-control study, liver tissue stiffness was determined using atomic force microscopy in cirrhotic livers (n = 38) of different etiologies and in controls (n = 10). Immunohistochemical and qRT-PCR analyses were performed to analyze TAZ expression. Besides, western blotting and ELISA were performed to assess liver Indian hedgehog and serum OPN levels, respectively. Liver stiffness, TAZ expression, and hepatic gene expression and serum protein levels of OPN were significantly increased in patients with cirrhosis compared with the control groups (all P < 0.001), specifically in autoimmune- and alcohol-related cirrhosis. In cirrhotic patients, liver stiffness was significantly associated with the expression of nuclear TAZ and OPN. The correlation between matrix stiffness as a mechanical property, TAZ as a potential mechanotransducer, and OPN as a matricellular factor suggests possible effects of mechanical features of the ECM on the expression of the aforementioned profibrogenic markers, which is predominant in autoimmune- and alcohol-related cirrhosis.


Subject(s)
Extracellular Matrix/genetics , Liver Cirrhosis/blood , Liver/metabolism , Osteopontin/blood , Adult , Alcohol-Related Disorders/blood , Alcohol-Related Disorders/genetics , Alcohol-Related Disorders/pathology , Case-Control Studies , Extracellular Matrix/pathology , Female , Gene Expression Regulation/genetics , Hedgehog Proteins/genetics , Humans , Liver/pathology , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Male , Middle Aged , Osteopontin/genetics
15.
J Gastrointest Cancer ; 51(3): 939-946, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31729644

ABSTRACT

PURPOSE: One of the worst types of cancers is gastric cancer and no specific tumor marker is found in relation to it. Reactive oxygen species modulator 1 (ROMO1) and the overlapping with the M-AAA protease 1 homolog (OMA1) proteins are the most important mitochondrial membrane proteins, which are involved in modulating reactive oxygen species (ROS) production and the regulation of mitochondrial structure dynamics. If these proteins do not function properly, oxidative stress increases in the cell, and this can initiate the cancer or worsen the condition. METHODS: In this study, ROMO1 and OMA1 gene expressions in 40 fresh frozen gastric cancer tissue and healthy adjacent tissues were evaluated by real-time PCR, and some of the important parameters related to oxidative stress such as TAC, TOS, MDA, and TTG in the serum of cancer patients compared to healthy people were measured by spectrophotometric and fluorometric techniques. RESULTS: We observed that ROMO1 and OMA1 gene expressions in gastric cancer tissues increased compared to that in healthy adjacent tissues. In addition, oxidative stress parameters including TOS, OSI, and MDA in the serum of cancer patients have increased significantly and the parameters including TAC and TTG have decreased. CONCLUSION: The results in our study represented that ROMO1 and OMA1 gene expressions in gastric cancer tissue have increased compared to that in healthy adjacent tissues, and oxidative stress levels have also increased significantly in relation to these proteins; therefore, these two proteins may be considered as an important cause of gastric cancer, and even introduced as tumor markers.


Subject(s)
Biomarkers, Tumor/metabolism , Membrane Proteins/metabolism , Metalloendopeptidases/metabolism , Mitochondrial Proteins/metabolism , Stomach Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Membrane Proteins/genetics , Metalloendopeptidases/genetics , Middle Aged , Mitochondrial Proteins/genetics , Oxidative Stress , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/surgery , Survival Rate
16.
Eur J Gastroenterol Hepatol ; 32(7): 844-850, 2020 07.
Article in English | MEDLINE | ID: mdl-31688307

ABSTRACT

BACKGROUND AND AIM: Cirrhosis is a major public health problem worldwide. The prevalence of cirrhosis is various in different geographical regions. The aim of the present study was to determine the distribution of the etiologies of cirrhosis and their proportional changes through recent 11 years in Iran. METHODS: In this retrospective, observational study, the data of cirrhotic patients who have been listed for liver transplantation in the Namazi Transplant Center (Shiraz, Iran) between January 2006 and December 2016 were analyzed. Demographic and clinical data of the patients including model for end-stage liver disease score, year of registration, and the etiologic diagnosis for each patient were retrieved. RESULTS: The ratio of males to females was the highest (2.6:1) in patients with age over 50 years. Of 4891 patients, hepatitis B virus cirrhosis had the highest frequency (23.53%) and alcoholic cirrhosis had the lowest frequency (1.70%). The percentages of waiting list patients with hepatitis B virus (34.48%-17.48%) (P < 0.001), autoimmune hepatitis (12.64%-8.50%) (P = 0.037), and alcoholic cirrhosis (2.30%-1.10%) were decreased (P = 0.008) and the percentages of waiting list patients with cholestatic (12.64%-25.20%) and nonalcoholic steatohepatitis cirrhosis (0.77%-8.82%) were increased over 11 years (both P < 0.001). Hepatitis B virus and autoimmune hepatitis cirrhosis were the most prevalent in male and female patients, respectively. CONCLUSION: The results of the present study showed an increase in the frequency of cholestasis and nonalcoholic steatohepatitis cirrhosis and therefore it should be considered in the health policy implementation.


Subject(s)
End Stage Liver Disease , Liver Transplantation , End Stage Liver Disease/epidemiology , End Stage Liver Disease/surgery , Female , Humans , Iran/epidemiology , Liver Cirrhosis/epidemiology , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Waiting Lists
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-865408

ABSTRACT

Objective: To evaluate the effect of resveratrol against CCl4-induced nephrotoxicity. Methods: Forty-two male Wistar rats were divided into seven groups randomly. After six weeks, kidney weight, body weight, blood urea, serum creatinine, oxidative stress markers, and gene expression of renal transforming growth factor-beta1 (TGF-β1), TGF-β receptor type 1 (TGF-βR1) and Smad3 were determined. In addition, the protein level of TGF-β1 in the tissue lysate was measured. Results: Resveratrol had a protective role in renal tissue by the improvement of antioxidant balance and reduction of renal parameters such as creatinine and urea (P<0.001). In addition, the renal mRNA level of TGF-β1, TGF-βR1, Smad3, as well as the protein level of TGF-β1 were decreased in rats treated with resveratrol (P<0.001), compared to the CCl4 group. Conclusions: Overall, resveratrol shows a protective effect against nephrotoxicity in CCl4 treated rats by reducing oxidative stress status and modulating the TGF-β signaling.

18.
Clin Lab ; 65(11)2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31710446

ABSTRACT

BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8) is a circulatory hormone that plays an important role in the proliferation of the pancreatic beta cells and lipid metabolism. MicroRNAs (miRs) are small non-coding RNAs that play an important role in the pathogenesis of diabetes mellitus. Therefore, we investigated the correlation of miR-103 and miR-133a expression with the ANGPTL8 and other type 2 diabetes mellitus (T2DM)-related factors. METHODS: Seventy subjects (controls: n = 35 and type 2 diabetic patients: n = 35) participated in this study. The ANGPTL8 concentration and miR-103/133a expression were measured using ELISA and real-time PCR, respectively. RESULTS: The circulatory ANGPTL8 concentration and miR-103/133a expression was significantly higher in T2D patients than in healthy controls (p < 0.05). There was a positive and significant correlation between miR-103/133a with triglycerides (TG), total cholesterol, fasting blood sugar (FBS), and glycated hemoglobin (p < 0.05) in the T2D group. The results also showed a negative and significant correlation between miR-103/133a expression with ANGPTL8 levels in the T2D group (p < 0.05). CONCLUSIONS: Our results suggest that miR-103/133a expression is correlated with the ANGPTL8 and T2D-related factors.


Subject(s)
Angiopoietin-like Proteins/blood , Circulating MicroRNA/blood , Diabetes Mellitus, Type 2/blood , MicroRNAs/blood , Peptide Hormones/blood , Aged , Angiopoietin-Like Protein 8 , Biomarkers/blood , Case-Control Studies , Circulating MicroRNA/genetics , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , MicroRNAs/genetics , Middle Aged , Real-Time Polymerase Chain Reaction , Up-Regulation
19.
Life Sci ; 237: 116904, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-31606380

ABSTRACT

AIMS: Long non-coding RNAs (LncRNAs) play central roles in the formation and development of gastric cancer (GC). The aim of this study was to evaluate the expression of PURPL and NONHSAT062994 and the relationship between their expressions with clinical characteristics in GC. MAIN METHODS: PURPL and NONHSAT062994 LncRNAs and p53 gene expression levels were analyzed both in 50 pairs of cancerous and adjacent noncancerous tissue samples in GC patients using qRT-PCR and in four sets of data obtained from Gene Expression Omnibus (GEO) database. Chi-square (χ2) test was used to determine the relationship between PURPL, NONHSAT062994 RNA levels and the clinicopathological characteristics of GC. Receiver operating characteristic (ROC) curves were drawn to represent sensitivity and specificity of PURPL and NONHSAT062994 expression as markers of GC. KEY FINDINGS: Expression of PURPL was significantly upregulated in 50 GC samples as well as in GC tissues from GSE13911 and GSE27342 datasets. Our results demonstrated that PURPL RNA level in GC was significantly related to tumor size and histopathological grade. p53 expression at both protein and mRNA levels were significantly decreased in GC tissues compared to adjacent control samples. NONHSAT062994 expression was downregulated in 50-pair GC and GC tissues from GSE13915 dataset. However, NONHSAT062994 showed no consistently differential expression in GSE2637dataset. NONHSAT062994 was significantly associated with histological grade and tumor size. SIGNIFICANCE: Overall, these results suggest that PURPL and NONHSAT062994 may play critical roles in the progression of GC and therefore might be considered as candidate tumor markers for therapeutic goals.


Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , RNA, Long Noncoding/genetics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Case-Control Studies , Cell Proliferation , Down-Regulation , Female , Humans , Male , Middle Aged , ROC Curve , Tumor Cells, Cultured
20.
Avicenna J Phytomed ; 9(5): 482-490, 2019.
Article in English | MEDLINE | ID: mdl-31516862

ABSTRACT

OBJECTIVE: The effects of kiwifruit on the histology and cell size of adipose tissue in hyperlipidemic models have not yet been reported. Therefore, this study aimed to investigate the effect of kiwifruit on the adipose tissue cell size and activity as well as the gene expression of cholesteryl ester transfer protein (CETP) in high-fat diet (HFD) fed hamsters. MATERIALS AND METHODS: Forty-two male Syrian hamsters were divided into six groups. Control normal (CN) hamsters received normal diet, control HFD (CHF) were fed with a HFD plus a normal diet (15% butter fat + 0.05% cholesterol + a normal diet). Two groups were fed with normal diet including kiwifruit (1.86; Nd.1 or 3.73 g/kg; Nd.2) and two groups were fed with HFD including kiwifruit (1.86;HFd.1or 3.73 g/kg; HFd.2), for 8 weeks. RESULTS: Histological examination of adipose tissue showed that the cell size was significantly reduced in the kiwifruit-treated groups (low and high dose) in comparison to their control groups (p<0.05). Kiwifruit supplementation (low and high dose) in normal and HFD groups significantly increased gene expression of CETP in adipose tissue. Kiwifruit had no significant effect on serum concentration of low-density lipoprotein cholesterol, total cholesterol and triglyceride. Although, high-density lipoprotein cholesterol concentration increased in HFD-fed hamsters supplemented with 3.73 g/kg of kiwifruit (p<0.05). CONCLUSION: Kiwifruit consumption reduces the size of adipocytes and increases the expression of CETP gene in adipose tissue cells. Despite the increases in CETP expression in adipose tissue, its activity in serum was not changed following kiwifruit supplementation.

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