Peripheral blood mononuclear cells show markers of mitochondrial dysfunction in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Metabolic and mitochondrial dysregulation are critical causal factors in the pathogenesis and progression of RA. Mitochondrial dysfunction include abnormal energy metabolism, and excessive production of reactive oxygen species (ROS). This study aimed to investigate the adenosine triphosphate (ATP), mitochondrial membrane potential (ΔΨm), ROS, and mRNA expression level of ROMO1 (as ROS modulator) and OMA1 (as regulator mitochondrial dynamics) of peripheral blood mononuclear cells (PBMC) in RA patients. The study participants were 50 patients with RA and 50 sex- and age-matched healthy volunteers. PBMC of all participant were isolated by Ficoll-Paque. Alteration in ΔΨm and cellular ROS were measured using flow cytometry, ATP level was also assessed via luminometry, and ROMO1 and OMA1 mRNA expression via qRT-PCR assay. A significant decrease in ATP (p = .005) and ΔΨm (p < .001) was observed in the PBMC of RA compared to control. The ROS levels were significantly higher in the PBMC of RA compared to the control (p < .001). ROMO1 and OMA1 mRNA expression was also significantly increased in RA patients compared to control (p < .001). The decrease in ATP is strongly associated with ROS increasing in PBMC of RA patients, denoting an inverse and negative relationship between ATP and ROS production. Also, a decrease in ΔΨm was observed. It seems that in line with mitochondrial dysfunction in PBMC, increased expression of ROMO1 and OMA1 genes could also be involved in the development of RA.

Uncovering the relationship between YAP/ WWTR1 (TAZ) genes expression and LncRNAs of SNHG15, HCP5 and LINC01433 in breast cancer tissues.

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.

Toxicity and Hepatoprotective Effects of ZnO Nanoparticles on Normal and High-Fat Diet-Fed Rat Livers: Mechanism of Action.

This experiment aimed to evaluate the beneficial and toxic properties of synthetic zinc oxide nanoparticles (ZnO NPs) on the liver of normal and high-fat diet (HFD) fed-rats. The ZnO NPs were synthesized and, its characterizations were determined by different techniques. Effect of ZnO NP on cell viability, liver enzymes and lipid accumulation were measured in HepG2 cells after 24 h. After that, rats orally received various dosages of ZnO NPs for period of 4 weeks. Toxicity tests were done to determine the appropriate dose. In the subsequent step, the hepatoprotective effects of 5 mg/kg ZnO NPs were determined in HFD-fed rats (experiment 2). The oxidative stress, NLRP3 inflammasome, inflammatory, and apoptosis pathways were measured. Additionally, the activity of caspase 3, nitric oxide levels, antioxidant capacity, and various biochemical factors were measured. Morphological changes in the rat livers were also evaluated by hematoxylin and eosin (H & E) and Masson trichrome. Liver apoptosis rate was also approved by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Treatment of animals with 5 mg/ZnO NPs revealed potential hepatoprotective properties, while ZnO NPs at the doses of above 10 mg/kg showed toxic effects. Antioxidant enzyme gene expression and activity were significantly augmented, while apoptosis, NLRP3 inflammasome, and inflammation pathways were significantly reduced by 5 mg/kg ZnO NPs. Liver histopathological alterations were restored by 5 mg/kg ZnO NPs in HFD. Our study highlights the hepatoprotective effects of ZnO NPs against the HFD-induced liver damage, involving antioxidant, anti-inflammatory, and anti-apoptotic pathways, indicating their promising therapeutic potential.

The Effects of Coenzyme Q10 on Contrast-Induced Acute Kidney Injury in Type 2 Diabetes: A Randomized Clinical Trial.

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.

Unveiling Arformoterol as a potent LSD1 inhibitor for breast cancer treatment: A comprehensive study integrating 3D-QSAR pharmacophore modeling, molecular docking, molecular dynamics simulations and in vitro assays.

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.

Determination of Osteoblast Cell Viability and Histological Changes of Samples Obtained from Different Implant Drills during Osteotomy.

Statement of the Problem: The bone particles collected during osteotomy could be used as autogenous bone graft materials for dental implant surgery. Different factors such as drill design may influence its clinical viability. Purpose: This study examined the effect of drill design on the osteoblast viability and histopathology parameters of bone collected during the preparation of dental implant site. Materials and Method: In this experimental study, 90 samples were obtained from three different bone drilling systems including Bego, Implantium, and Dio during fixture installation in patients requiring treatment at the Department of Periodontology, Dentistry University Hamedan. The MTT (3-4,5-Dimethylthiazol2,5-diphenyltetrazolium bromide) was used to determine percentage of cell viability. Samples were fixed in 10% formaldehyde for histological evaluation. Then, they were kept in 10% EDTA solution for 4 weeks for decalcification. The provided slides were evaluated regarding bone structure and osteocytes counts for assessment of viability. Tukey test and SPPS 21 software were used for statistical analysis. Results: The result showed the viability of osteoblast obtained by Dio (0.45±0.04) was significantly better than Bego (0.37±0.05) and Implantium (0.37±0.04) systems. In histopathological evaluation, the grafting material obtained by Dio presented the best osteoblast morphology. Conclusion: It might be concluded that drill geometry has significantly influenced the viability of bone particles collected during the preparation of implant sites .Moreover, characteristic geometry alone cannot represent the performance of a particular drill, and several geometric features should be concerned. The results of this study showed that the geometry of the Dio drill was the best considering the viability and histopathological evaluations.

Antidiabetic Effects of Genistein: Mechanism of Action.

Diabetes mellitus is a metabolic disease recognized by abnormal glucose level due to defects in insulin action, insulin secretion, or both. Administration of soybean and isoflavones are accompanied by a lower risk of diabetes. The present review analyzed the previous published papers related to genistein. This isoflavone, which has been used for the prevention of some chronic diseases can inhibit hepatic glucose production, increase ß-cell proliferation, reduce ß-cell apoptosis, and show potential antioxidant and anti-diabetic effects. Therefore, genistein may be useful in the management of diabetes. The beneficial effects of this isoflavone on metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, and cancer have been reported in animal and human studies. Moreover, genistein reduces hepatic glucose production, normalizes hyperglycemia, and gut microbiota and exhibits potential anti-oxidative, anti-apoptotic, and hypolipidemic effects. However, studies on the underlying mechanisms of the action of genistein are very limited. Therefore, the present study reviews multifaceted aspects of genistein to reveal a possible anti-diabetic mechanism of this agent. Genistein by regulating several signaling pathways can be used for the prevention and management of diabetes.

Granulosa cells from immature follicles exhibit restricted glycolysis and reduced energy production: a dominant problem in polycystic ovary syndrome.

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.

The Association of Mitochondrial Translocator Protein and Voltage-Dependent Anion Channel-1 in Granulosa Cells with Estradiol Levels and Presence of Immature Follicles in Polycystic Ovary Syndrome.

Background: Granulosa cells (GCs) play key roles in oocyte maturation by providing required estradiol (E2). Since the presence of immature oocytes has been reported in cases with polycystic ovary syndrome (PCOS), in this study, the levels of mitochondrial membrane transporter proteins involved in E2 synthesis were determined. E2 concentration and parameters of oxidative status were also measured in follicular fluids of PCOS women. Methods: Forty-three women with PCOS and 43 healthy women who were candidates for IVF procedure due to their husbands' infertility were enrolled in this case-control study. The gene expression and protein levels of mitochondrial translocator protein (TSPO) and voltage-dependent anion channel 1 (VDAC1) were determined in GCs using RT-qPCR and immunocytochemistry assay, respectively. E2 level was measured with electrochemiluminescence, whereas total cholesterol, total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) were determined using colorimetric methods in follicular fluids. Data were analyzed using unpaired t-test or Mann-Whitney U test, and Spearman's correlation coefficient. Results: VDAC1 and TSPO were significantly lower in mRNA (p<0.05) and protein levels (p<0.001) of PCOS patients. PCOS patients had lower cholesterol, estradiol, and TAC levels, and higher TOS and MDA contents. E2 level had direct correlation with VDAC1, TSPO, and TAC while it was negatively correlated with TOS, oxidative stress index (OSI), and MDA (p<0.001). Higher E2 levels were associated with higher numbers of high-quality oocytes and conceived embryos (p<0.001). Conclusion: Decreased E2 levels and increased oxidative stress in the follicular fluid may be the cause of immature oocytes in PCOS cases.

Effects of curcumin and metformin on oxidative stress and apoptosis in heart tissue of type 1 diabetic rats.

Introduction: Hyperglycemia enhances oxidative stress and apoptosis and induces damages in heart tissue. Based on antioxidant properties of curcumin and metformin, we hypothesized that these agents may exhibit cardioprotective effects by attenuating oxidative stress and modulating expression of the genes involved in apoptosis in type-1 diabetes. Methods: Thirty-six male rats were randomly divided into six groups; (N): control; (D): streptozotocin-induced diabetic rats; (D+Cur50) and (D+Cur150): diabetic rats treated with 50 and 150 milligram of curcumin per kilogram of body weight (mg/kg.bw), respectively; (D+Met300) and (D+Met500): diabetic rats received 300 and 500 mg/kg.bw of metformin, respectively. Heart tissues were dissected and gene expression levels of Bax, Bcl-2, and caspase-3 were analyzed. Total anti-oxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) level, and activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. Results: Enhancement in TOS, OSI, and MDA levels as well as increased in the activity of CAT and reduction in SOD and GPx activities were observed in diabetic group (D) compared with control rats. Treatment of diabetic animals with either curcumin or metformin normalized TOS, OSI, and MDA levels and restored CAT, SOD, and GPx activities. Diabetes caused extensive damages in heart tissue of rats (group D) and increased expression of caspase-3 and Bax genes and enhanced ratio of Bax/Bcl-2 expression compared with controls. Treatment with curcumin or metformin mitigated histopathological changes and dampened apoptosis by normalizing Bax and caspase-3 expression. Conclusion: Curcumin and metformin modulated diabetes-induced cardiac damage probably by reducing oxidative stress.

Beneficial effects of genistein in suppression of proliferation, inhibition of metastasis, and induction of apoptosis in PC3 prostate cancer cells.

OBJECTIVES: Beneficial effects of genistein have been studied in various cancer types but the underlying molecular mechanisms of its actions have not been well established. This study investigated the effects of genistein on caspase-3 and p38 mitogen-activated protein kinase (p38MAPK) as main cellular signalling targets in PC3 prostate cancer cells. METHODS: Caspase-3 and p38MAPK gene expression and intracellular protein levels were determined. Matrix metalloproteinase-2 (MMP2) gelatinase activity and caspase-3 enzyme activity were measured and PC3 cell migration and proliferation potencies were assessed. RESULTS: Genistein induced apoptosis by enhancing the gene expression, intracellular protein level, and enzyme activity of caspase-3. Genistein also inhibited cell proliferation by reducing p38MAPK gene expression and protein level and strongly suppressed metastatic potency of PC3 cells by reducing MMP2 activity. CONCLUSION: Genistein exhibits its beneficial anticancer properties on PC3 cells by reducing metastatic potency and regulating caspase-3 and p38MAPK pathways at different transcriptional and protein levels.

The role of Acanthamoeba castellanii (T4 genotype) antioxidant enzymes in parasite survival under H2O2-induced oxidative stress.

Acanthamoeba castellanii (A. castellanii) is an important opportunistic parasite. Induction of oxidative stress by the host immune system is one of the most important defense strategies against parasites. Hence, parasites partly deal with oxidative stress by different mechanisms. Identifying resistance mechanisms of A. castellanii parasites against oxidative stress is important to achieve a new therapeutic approach. Thus, this study aimed to understand the resistance mechanisms of A. castellanii, against oxidative stress. Trophozoites of A. castellanii were treated with different concentrations of H2O2. The half maximal inhibitory concentration (IC50) of H2O2 was determined using the MTT assay. The induction of oxidative stress was confirmed by flow cytometer. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were determined. The gene expression levels of CAT and SOD were measured by qRT-PCR. Furthermore, 3-amino-1:2:4-triazole (3-AT) and potassium cyanide (KCN) were used as specific inhibitors of CAT and SOD, respectively. Cell cycle assay and the apoptosis were evaluated by flow cytometer. The activities of SOD, CAT, GR, and GPx, showed an increase in oxidative stress. The cell cycle analysis revealed that most of the cellular population was in G0 and G1 phases. The apoptosis increased in oxidative stress conditions. Moreover, the apoptosis significantly increased after the specific inhibition of CAT and SOD under oxidative stress. The gene expression levels of CAT and SOD significantly increased under oxidative stress. A. castellanii can resist the host immune system through various mechanisms, including evoking its antioxidant enzymes. Therefore, by reducing or inhibiting the activity of the parasite's antioxidant enzymes such as SOD and CAT, it is possible to cope with A. castellanii.

Aspartate Aminotransferase-To-Platelet Ratio Index: a Potential Predictor of Prognosis in the Most Common Types of Cirrhosis.

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.

Favorable effects of Anethum graveolens on liver oxidative stress and cholesterol 7 alpha-hydroxylase levels in non-alcoholic fatty liver disease (NAFLD) rat models.

BACKGROUND: High-fat high-cholesterol diet induces a phenotype similar to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in humans. In NAFLD and NASH, cholesterol and bile acid metabolisms are impaired to accumulate lipids and toxic bile acids along with cholestatic hepatic damage. Recently, the use of herbal-derived cholesterol lowering products has attracted much attention as possible therapeutic strategies for NAFLD. Hence, the aim of this study was to determine the effects of an Anethum graveolens (dill) on liver cholesterol 7 alpha-hydroxylase and liver fat accumulation in rats. METHOD: Thirty-six rats were randomly divided into 6 groups (n = 6) and received normal diet (ND) or a mixture of chow diet+2% cholesterol+0.5% cholic acid + 20% corn oil as high cholesterol/fat (HC-HF) diet (NAFLD model). Animals were also treated daily with dill tablet or dill extract (300 mg/kg). At the end of the 30 days experiments, serum and liver lipid profile and liver total antioxidant capacity were determined. Cholesterol 7 alpha-hydroxylase mRNA and protein expression levels were determined in the liver and histopathological changes in liver tissues were analyzed by microscope. RESULTS: Lipid profiles significantly decreased in dill treated groups (p < 0.05). Liver total antioxidant capacity significantly (p < 0.05) increased and MDA levels markedly (p < 0.05) reduced both in dill tablet and dill extract treated groups (p < 0.05). Both types of treatments caused significant increases in liver cholesterol 7 alpha-hydroxylase gene expression (p < 0.05). Histopathological examinations showed that treatment with dill normalized the hypercholesterolemia-induced changes in liver histology. CONCLUSION: Administration of dill significantly reduced liver fat, oxidative stress and increased cholesterol 7 alpha-hydroxylase enzyme at the both mRNA and protein levels. Dill extract was found more effective than its commercially available tablet.

Diabetes and COVID-19: Mechanism of pneumonia, treatment strategy and vaccine.

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.

Transitional cell carcinoma matrix stiffness regulates the osteopontin and YAP expression in recurrent patients.

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.

NLRP3-inflammasome activation is associated with epithelial-mesenchymal transition and progression of colorectal cancer.

OBJECTIVES: Since activation of NLRP3 inflammasome results in the production of interleukin-1ß (IL 1ß) and initiation of inflammation as the key players in development of cancer, this study investigated possible activation of NLRP3 inflammasome during the progression of colorectal cancer (CRC) and evaluated the role of NLRP3 inflammasome in epithelial-mesenchymal transition (EMT) process. MATERIALS AND METHODS: Tissue samples were collected from cancerous (test) and adjacent normal tissues (control) of forty-three male CRC patients (18 grade I and 25 grade III). The gene expression and protein levels were determined by qRT PCR and Western blotting, respectively, and tissue morphological was examined by histopathology. RESULTS: The gene and protein expression levels of transforming growth factor-ß (TGF ß), IL 1ß, nuclear factor κB (NF κB), NLRP3, and caspase-1, as well as the enzyme activity of caspase-1, were significantly increased in CRC. mRNA and protein levels of TGF-ß, mature IL 1ß, NF κB, and NLRP3 were higher in patients with grade III. EMT markers N cadherin, vimentin, and MMP 9 markedly increased in CRC, and were higher in grade III than grade I, whereas expression of E-cadherin declined by the progression of CRC. NLRP3 protein level was inversely correlated with E-cadherin whereas it positively was correlated with IL 1ß, active NF κB, N cadherin, vimentin, and MMP 9. CONCLUSION: This study for the first time showed that activation of NLRP3 inflammasome contributed to the progression of CRC and is correlated with the EMT process. Although the present study showed that EMT markers are positively correlated with tumor grade, further investigations are required to strongly link the EMT markers to the progression of CRC.

Favorable effects of dill tablets and Ocimum basilicum L. extract on learning, memory, and hippocampal fatty acid composition in hypercholesterolemic rats.

OBJECTIVES: Hypercholesterolemia is correlated with brain amyloid-ß (Aß) deposition and impaired cognitive functions and contributes to Alzheimer's disease. Effects of cholesterol-lowering dill tablets and aqueous extract of Ocimum basilicum L. (basil) on learning and memory and hippocampus fatty acid composition were examined. mRNA levels of the genes involved in cholesterol homeostasis were also determined in high-cholesterol diet (HCD) fed rats. MATERIALS AND METHODS: Forty male Wistar rats were allocated to 4 groups: rats fed chow diet (C); rats fed high-cholesterol (2%) diet (HCD); rats treated with HCD+300 mg/kg dill tablets (HCD+Dill); and finally, rats fed HCD and treated with 400 mg/kg basil aqueous extract (HCD+basil). Treatment was carried out for 16 weeks. Hippocampus Aß(1-42) level was determined. Spatial and passive avoidance tests were used to examine cognitive functions. Hippocampal FA composition was assessed by gas chromatography. Basil aqueous extract was analyzed by GC-double mass spectroscopy (GC-MS/MS) and expression of LXR-α, LXR-ß, and ABCA1 genes was assessed by qRT-PCR. RESULTS: Dill tablets and basil extract remarkably ameliorated serum cholesterol (P<0.001), retarded hippocampal accumulation of Aß, and attenuated HCD-induced memory impairment. Hippocampus FA composition did not change but serum cholesterol was found positively correlated with hippocampus Aß(1-42) (P<0.001), total n 6 PUFA (P=0.013), and Aß(1-42) showed correlation with the ratio of n6 to n3 PUFA. At least 70 components were identified in basil aqueous extract. CONCLUSION: Dill tablets and aqueous extract of basil attenuated the hypercholesterolemia-induced memory impairment by lowering serum cholesterol and hippocampus amyloid deposits, and probably beneficial in AD adjuvant therapy.

Probiotic and resveratrol normalize GLP-1 levels and oxidative stress in the intestine of diabetic rats.

BACKGROUND: Recently, the use of incretins has been considered as a therapeutic target for diabetes. One of the important incretins in the improvement of diabetes is glucagon-like peptide (GLP-1), which is secreted by the gut and reduces the apoptosis of pancreatic ß-cells and improves insulin sensitivity. In this experiment we determined the effects of resveratrol and probiotics on insulin resistance, oxidative stress, and GLP-1 in type 2 diabetes (T2D) rats. METHODS: In this study, 40 male Wistar male rats were divided into 5 groups: 1. Control group, 2. T2D, 3. T2D treated with probiotics, 4. T2D treated with resveratrol, 5. T2D group treated with probiotics and resveratrol. After four weeks, the intestine were removed for histopathological analysis, biochemical tests, and oxidative stress markers. RESULTS: Probiotics and resveratrol significantly decreased (p < 0.001) glucose and insulin resistance, and increased (p < 0.001) GLP1 and total antioxidant capacity compared to the diabetic group. Treatment with probiotics and resveratrol also returned intestinal histological changes in diabetic rats to normal. CONCLUSION: Resveratrol and probiotics appear to be effective in controlling T2D by increasing GLP-1 levels and reducing oxidative stress.