Gender, Bladder Cancer Healthcare and Burden of COVID-19.

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.

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.

Effects of progesterone nanoparticles on the sperm capacitation and acrosome reaction in asthenozoospermia men.

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.

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.

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.

Carvacrol Downregulates Lysyl Oxidase Expression and Ameliorates Oxidative Stress in the Liver of Rats with Carbon Tetrachloride-Induced Liver Fibrosis.

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.

Downregulation of hedgehog ligands in human simple steatosis may protect against nonalcoholic steatohepatitis: Is TAZ a crucial regulator?

The conversion of simple steatosis into nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD) has attracted many attentions in recent years. The role of the hedgehog (HH) pathway in the regulation of lipogenesis has been addressed in the literature. This study aimed to investigate the levels of the sonic hedgehog (SHH) and Indian hedgehog (IHH) ligands and the correlation of these ligands with levels of proteins involved in the transforming growth factor-ß1 (TGF-ß1) pathway, as well as the evaluation of the transcriptional coactivator with PDZ binding motif (TAZ) expression in human simple steatosis, NASH cirrhosis, and controls. Patients were divided into two groups: the first group consisted of patients diagnosed with simple steatosis (n = 16) and the second group included those diagnosed with NASH cirrhosis (n = 15). As a control group, 18 histologically normal liver tissues were collected in this study. The expression of the TGF-ß1pathway components and SHH and IHH ligands were analyzed by means of the quantitative real-time polymerase chain reaction and western blot analyses. A significant decrease was found in the hepatic expression of the SHH, IHH, and TGF-ß1 pathways along with the expression of TAZ in tissue specimens with simple steatosis in comparison with patients affected by NASH cirrhosis and controls. Also, the levels of SHH and IHH proteins were significantly correlated with the expression of proteins involved in the TGF-ß1 pathway. Moreover, the expression of the HH pathway ligands was positively associated with the expression of TAZ, supporting the notion that TAZ may play a role in the activation of the HH pathway thereby regulating the expression of its ligands. It seems that in patients with NAFLD, the downregulation of the HH pathway ligands may stem from steatosis; however, at the same time, it may prevent the conversion of simple steatosis into NASH in patients with liver diseases. © 2019 IUBMB Life, 71(9):1382-1390, 2019.

Intricate role of yes-associated protein1 in human liver cirrhosis: TGF-ß1 still is a giant player.

Numerous investigations have been performed on the role of the transforming growth factor-ß1 (TGF-ß1) pathway in the development of chronic liver diseases (CLDs); however, they failed to explain the underlying mechanism of its pathogenesis, suggesting that other alternative pathways might have been overlooked. The involvement of yes-associated protein1 (YAP1) has been attributed to liver fibrosis; yet, the precise function of this protein has not been fully understood. Therefore, this study aimed to investigate the activity of the YAP1 pathway in human liver cirrhosis (regardless of its causality) and its correlation with the TGF-ß1 and sonic hedgehog (SHH) pathways. In this case-control study, the immunohistochemical and quantitative real-time polymerase chain reaction analyses were carried out to determine the activation of the YAP1 pathway in patients with liver cirrhosis (n = 38) and control 1 individuals (n = 10). The western blot analysis and ELISA method were also performed to assess the SHH and TGF-ß1 pathways. Although significantly increased expression of cytoplasmic YAP1 was found in patients with liver cirrhosis (P < 0.045), the rate of the nuclear YAP1 expression was similar to that of the control 1 subjects. Moreover, the hepatic expression of amphiregulin (AREG), known as the YAP1 target, along with proteins involved in the TGF-ß1 pathway was significantly elevated in all cirrhotic patients, compared with the control subjects. Our results showed that the increased activity of the TGF-ß1 pathway is strongly associated with the expression of AREG, denoting a direct and positive relationship between the TGF-ß1 and YAP1 pathways. It seems that, unlike the TGF-ß1 and SHH pathways, the YAP1 pathway does not play a significant role in the development of liver cirrhosis.

Correlation between miR-103 and miR-133a Expression and the Circulating ANGPTL8 in Type 2 Diabetic Patients and Healthy Control Subjects.

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.

Association between rs2278426 (C/T) and rs892066 (C/G) variants of ANGPTL8 (betatrophin) and susceptibility to type2 diabetes mellitus.

BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8) is a hormone that mainly secreted from the liver and adipose tissue and plays an important role in the proliferation of pancreatic beta cells and lipid metabolism. Therefore, we studied the association of ANGPTL8 rs2278426 (C/T) and rs892066 (C/G) polymorphisms with the risk of type 2 diabetes mellitus (T2DM) and their association with biochemical parameters. METHODS: Two hundred and eighty-eight subjects (controls; n = 138 and type 2 diabetic patients; n = 150) were enrolled in this study. Direct haplotyping was performed using amplification-refractory mutation system (ARMS)-RFLP-PCR. RESULTS: The CT genotype frequency of rs2278426 (C/T) variant was significantly higher in T2DM patients compared to the controls group (P = 0.02), and there was a significant association between this genotype and increased risk of T2DM (OR: 2.41, CI: 1.26-4.59, P = 0.007). In addition, there was a significant relationship between CT genotype of this variant and high-density lipoprotein cholesterol (HDL-C), fasting blood sugar (FBS), insulin, insulin resistance and glycated hemoglobin (P < 0.05). Furthermore, bioinformatics analysis revealed that arginine (Arg) to tryptophan (Trp) substitution at rs2278426 position causes structural instability of ANGPTL8 protein. Genotype and allele distribution of rs892066 (C/G) was not statistically significant in T2DM patients compared to the control group. The distribution of haplotypes had no significant difference between controls and T2DM patients (P = 0.24). CONCLUSION: Our results suggest that the rs2278426 (C/T) variant is associated with increased risk of T2DM and may cause dyslipidemia due to its effect on decreasing HDL-C levels.

Carvacrol ameliorates the progression of liver fibrosis through targeting of Hippo and TGF-ß signaling pathways in carbon tetrachloride (CCl4)-induced liver fibrosis in rats.

Objective: Little is known about the exact underlying molecular mechanisms of the hepatoprotective effect of carvacrol against liver fibrosis. In the current study, we aimed to investigate the effect of carvacrol on the suppression of liver fibrosis progression via regulation of yes-associated protein (YAP) and transcriptional coactivators with a PDZ-binding motif (TAZ) and transforming growth factor beta (TGF-ß) pathway. Materials and methods: To fulfill our target, rats received carbon tetrachloride (CCl4) and carvacrol intraperitoneally, and orally, respectively for 10 weeks. Body weight, liver weight, serum biochemical parameters, hepatic hydroxyproline content, and histological changes were determined. Furthermore, gene expression of collagen and key elements of Hippo and TGF-ß pathways were analyzed and then the protein levels of YAP, TAZ, and TGF-ß were detected in liver tissue. Results: Carvacrol administration normalized liver and body weight, serum biochemical parameters and hepatic hydroxyproline in CCl4 treated rats. Also, carvacrol downregulated TAZ and TGF-ß signaling pathway at transcriptional levels. Furthermore, carvacrol decreased hepatic protein levels of TGF-ß, TAZ, and YAP. Low expression of TAZ and YAP were accompanied with inhibition of TGF-ß signaling pathway. Conclusion: Our data clearly revealed that carvacrol suppresses the progression of liver fibrosis via targeting of TAZ, YAP, and TGF-ß signaling pathway.

Sperm matrix metalloproteinase-2 activity increased in pregnant couples treated with intrauterine insemination: a prospective case control study.

Matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) have an important role in the reproductive system and in the fertilisation process. The aim of this study was to investigate the MMP2 and MMP9 activity in semen and their association with the pregnancy rate, semen parameters and seminal plasma oxidative stress parameters in couples who were treated with intrauterine insemination (IUI). The semen specimens were obtained from 60 men who attended with their spouse for the IUI in the infertility unit. A controlled ovarian stimulation was performed with clomiphene citrate in IUI cycles. Women with positive pregnancies were recorded (n = 29). The results showed the activity of sperm MMP2 and seminal plasma MMP9 was significantly higher in the pregnant group, compared to the non-pregnant group (p < .05). There was a correlation between the sperm MMP2 activity and the total thiol group (TTG) (r = 0.276, p < .05) and the total antioxidant capacity (TAC) of seminal plasma (r = 0.304, p < .05). The sperm MMP9 showed a positive correlation with the seminal plasma TAC (r = 0.330, p < .05) and an inverse correlation with the lipid peroxidation (LP) of seminal plasma (r = -304, p< 0.05). In addition, the seminal plasma MMP2 activity was correlated to sperm viability (r = 0.266, p< .05) and the TTG of seminal plasma (r = 0.298, p < .05). The MMP2 activity in the sperm may be an important factor for determining the pregnancy rate after IUI. Impact statement What is already known on this subject? Previous studies have reported that the fusion between the sperm and zona pellucida required the activity of matrix metalloproteinase 2 (MMP2), whereas the inhibition of MMP2 can significantly decrease the in vitro fertilisation (IVF) rate. What do the results of this study add? This study has identified that the sperm MMP2 activity was significantly higher in the pregnant couples in comparison with the non-pregnant couples, who treated with intrauterine insemination (IUI). The findings showed there was a correlation between sperm MMP2 activity and the total thiol group (TTG) and the total antioxidant capacity (TAC) of the seminal plasma. What are the implications of these findings for clinical practice and/or further research? MMP2 activity in the sperm could influence the IUI outcome and it is an important factor for IUI success.

Hepatoprotective Effects of Silymarin on Liver Injury via Irisin Upregulation and Oxidative Stress Reduction in Rats with Type 2 Diabetes.

BACKGROUND: Diabetes is one of the most prevalent metabolic diseases. Irisin (FNDC5 protein) is involved in the new strategy of combating type 2 diabetes. In the liver, the antidiabetic mechanism of silymarin at the molecular level is unknown. This study investigated the effects of silymarin on irisin and the related gene expression and oxidative stress status in the liver of type 2 diabetic rats. METHODS: Thirty-six rats were divided into 6 groups (n=6 each) by simple randomization: control, control+silymarin (60 mg/kg daily in normal saline orally for 60 days), control+silymarin (120 mg/kg daily in normal saline orally for 60 days), diabetic, diabetic+silymarin (60 mg/kg daily for 60 days), and diabetic+silymarin (120 mg/kg daily for 60 days). Biochemical parameters were measured by spectrophotometric and immunoassay methods, and quantitative polymerase chain reaction was used to evaluate gene expression. The data were analyzed by one-way ANOVA, followed by the Tukey test, using SPSS software, version 16.0. The results were considered statistically significant at a P value less than 0.05. RESULTS: In the diabetic rats treated with silymarin (60 and 120 mg/kg), by comparison with the diabetic group, body weight (P=0.04 and P=0.02), insulin (P<0.001), expression of PGC-1α (P=0.04 and P=0.02), expression of FNDC5 (P=0.03 and P=0.01), and concentration of irisin in the liver (P=0.02 and P=0.01) and serum (P<0.001) were significantly increased, whereas the levels of glucose (P<0.001), HOMA-IR (P=0.03 and P=0.01), and liver injury markers (P<0.001) were significantly reduced. Oxidative stress status and histopathological changes were improved in the treated groups. CONCLUSION: These results suggest that silymarin because of its ability to upregulate irisin and antioxidant effects can be considered an antidiabetic agent.

Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS.

It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.

Association between GSTM1, GSTT1, and GSTP1 variants and the risk of end stage renal disease.

INTRODUCTION: There are some evidences indicating DNA damage by oxidant and mutant agents has an essential role in the chronic renal failure and end stage renal disease (ESRD). To investigate the possible association of GSTs variants with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and the level of malondialdehyde (MDA) in patients with ESRD. MATERIALS AND METHODS: The present case-control study consisted of 136 ESRD patients treated with maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of MDA was measured by high-performance liquid chromatography (HPLC). RESULTS: We found that GSTM1 and GSTT1 null genotypes (GSTT1-/GSTM1-) increased the risk of ESRD by 1.8 times (p < 0.001) and the increased risk of ESRD for GSTM-null (T1+-M1-) genotype was 3.04 times (p = 0.002). ESRD patients carriers the GST (GSTM1-null + GSTT1-null + GST-null) genotypes compared to GST normal genotype increased the risk of ESRD by 3.3 (p < 0.001) times. ESRD patients carriers of GST-null, GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with the same genotypes of control subjects. Our results indicated that the GST-null allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this allele have high levels of MDA. CONCLUSION: Our findings indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of ESRD and its related complications. These data suggest that patients with ESRD are more susceptible to vascular diseases.

PROTECTIVE EFFECTS OF GLUTATHIONE SUPPLEMENTATION AGAINST OXIDATIVE STRESS DURING CRYOPRESERVATION OF HUMAN SPERMATOZOA.

BACKGROUND: Freeze damage is one of the most important factors which impair the membrane and DNA integrity of sperm cells. OBJECTIVE: The present study aims to investigate glutathione (GSH) supplementation on human spermatozoa cryopreservation. We determined sperm motility and viability, sperm lipid peroxidation, DNA damage, and the amount of hydrogen peroxide (H(2)O(2)) and superoxide (O(2)(-)). MATERIALS AND METHODS: Twenty pooled semen samples were freeze with 5mM GSH for 10 minute (test) and without GSH as control and stored in liquid nitrogen. RESULTS: After thawing, cryovials supplemented with 5mM GSH led to higher sperm viability compared with control samples (p < 0.05). Furthermore, the addition of 5mM GSH decreased sperm lipid peroxidation, DNA fragmentation, and H(2)O(2) and O(2)(-) content compared with controls (p < 0.05). CONCLUSION: GSH can be a good free radical scavenger in the freezing media and can support function of sperm cell after a cycle of freezing and thawing.

Aqueous Extract of Anethum Graveolens L. has Potential Antioxidant and Antiglycation Effects.

The aim of this study was to assess the antiglycation and antioxidant properties of aqueous extract of Anethum graveolens (dill). In the in vivo and in vitro experiments, antioxidant properties, blood glucose, and AGEs formation were determined. Dill extract was given orally to healthy and diabetic rats. Our results illustrated that different concentrations of dill extract (0.125, 0.25, 0.5, and 1 mg/ml) have potential antiradical and antioxidant activity. Aqueous extract of dill significantly reduced AGEs formation and fructosamine levels, protein carbonyl and also thiol group's oxidation, amyloid cross-ß and fragmentation. After 2 months, blood glucose levels (P=0.006) and AGEs formation (P=0.003) significantly reduced in dill treated group compared with untreated diabetic animals. In conclusion, dill can be recommended as herbal medicine for the control and prevention of diabetic complications.

Association of functional polymorphisms in FAS and FAS Ligand genes promoter with pre-eclampsia.

AIM: Pre-eclampsia (PE) is a complex disorder of pregnancy with unknown etiology. FAS-mediated apoptosis is assumed to prevent the development of PE; therefore FAS and FAS Ligand may be represented as candidate genes involved in PE pathogenesis. In the present study, we evaluated the relation between FAS Ligand A-670G (rs1800682) and FAS Ligand C-844T (rs763110) gene polymorphisms with PE in southeast Iran. METHODS: One hundred and twenty-seven unrelated women with PE and 139 healthy control subjects were genotyped for the FAS A-670G and FAS Ligand C-844T polymorphisms by polymerase chain reaction restriction fragment length polymorphism method. RESULTS: The AA, AG and GG genotype frequency of the FAS A-670G polymorphism were 21.3%, 53.5% and 25.2% in pre-eclamptic women and 46.0%, 41.5% and 11.5% in controls and were statistically different (P = 0.0001). The risk of PE was 2.7- and 4.7-fold higher in pregnant women with AG and GG genotypes respectively. Although the frequency TT genotype and T allele of FAS Ligand C-844T gene polymorphism was higher in the PE group, the differences were not significant. CONCLUSION: FAS A-670G polymorphism is associated with a higher risk for PE. There was no association between FAS Ligand C-844T polymorphism and PE.

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.

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.