Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures

Background: Mounting studies indicate that oxidative stress (OS) significantly contributes to tumor progression. Our study focused on bladder urothelial cancer (BLCA), an escalating malignancy worldwide that is growing rapidly. Our objective was to verify the predictive precision of genes associated with overall survival (OS) by constructing a model that forecasts outcomes for bladder cancer and evaluates the prognostic importance of these genetic markers. Methods: Transcriptomic data were obtained from TCGA-BLCA and GSE31684, which are components of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. To delineate distinct molecular subtypes, we employed the non-negative matrix factorization (NMF)method. The significance of OS-associated genes in predicting outcomes was assessed using lasso regression, multivariate Cox analysis, and univariate Cox regression analysis. For external validation, we employed the GSE31684 dataset. CIBERSORT was utilized to examine the tumor immune microenvironment (TIME). A nomogram was created and verified using calibration and receiver operating characteristic (ROC) curves, which are based on risk signatures. We examined variations in clinical characteristics and tumor mutational burden (TMB) among groups classified as high-risk and low-risk. To evaluate the potential of immunotherapy, the immune phenomenon score (IPS) was computed based on the risk score. In the end, the pRRophetic algorithm was employed to forecast the IC50 values of chemotherapy medications. Results: In our research, we examined the expression of 275 genes associated with OS in 19 healthy and 414 cancerous tissues of the bladder obtained from the TCGA database. As a result, a new risk signature was created that includes 4 genes associated with OS (RBPMS, CRYAB, P4HB, and PDGFRA). We found two separate groups, C1 and C2, that showed notable variations in immune cells and stromal score. According to the Kaplan-Meier analysis, patients classified as high-risk experienced a considerably reduced overall survival in comparison to those categorized as low-risk (P<0.001). The predictive capability of the model was indicated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve surpassing 0.6. Our model showed consistent distribution of samples from both the GEO database and TCGA data. Both the univariate and multivariate Cox regression analyses validated the importance of the risk score in relation to overall survival (P < 0.001). According to our research, patients with a lower risk profile may experience greater advantages from using a CTLA4 inhibitor, whereas patients with a higher risk profile demonstrated a higher level of responsiveness to Paclitaxel and Cisplatin. In addition, methotrexate exhibited a more positive outcome in patients with low risk compared to those with high risk. Conclusions: Our research introduces a novel model associated with OS gene signature in bladder cancer, which uncovers unique survival results. This model can assist in tailoring personalized treatment approaches and enhancing patient therapeutic effect in the management of bladder cancer

Prognostic model development and molecular subtypes identification in bladder urothelial cancer by oxidative stress signatures

Background: Mounting studies indicate that oxidative stress (OS) significantly contributes to tumor progression. Our study focused on bladder urothelial cancer (BLCA), an escalating malignancy worldwide that is growing rapidly. Our objective was to verify the predictive precision of genes associated with overall survival (OS) by constructing a model that forecasts outcomes for bladder cancer and evaluates the prognostic importance of these genetic markers. Methods: Transcriptomic data were obtained from TCGA-BLCA and GSE31684, which are components of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. To delineate distinct molecular subtypes, we employed the non-negative matrix factorization (NMF)method. The significance of OS-associated genes in predicting outcomes was assessed using lasso regression, multivariate Cox analysis, and univariate Cox regression analysis. For external validation, we employed the GSE31684 dataset. CIBERSORT was utilized to examine the tumor immune microenvironment (TIME). A nomogram was created and verified using calibration and receiver operating characteristic (ROC) curves, which are based on risk signatures. We examined variations in clinical characteristics and tumor mutational burden (TMB) among groups classified as high-risk and low-risk. To evaluate the potential of immunotherapy, the immune phenomenon score (IPS) was computed based on the risk score. In the end, the pRRophetic algorithm was employed to forecast the IC50 values of chemotherapy medications. Results: In our research, we examined the expression of 275 genes associated with OS in 19 healthy and 414 cancerous tissues of the bladder obtained from the TCGA database. As a result, a new risk signature was created that includes 4 genes associated with OS (RBPMS, CRYAB, P4HB, and PDGFRA). We found two separate groups, C1 and C2, that showed notable variations in immune cells and stromal score. According to the Kaplan-Meier analysis, patients classified as high-risk experienced a considerably reduced overall survival in comparison to those categorized as low-risk (P<0.001). The predictive capability of the model was indicated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve surpassing 0.6. Our model showed consistent distribution of samples from both the GEO database and TCGA data. Both the univariate and multivariate Cox regression analyses validated the importance of the risk score in relation to overall survival (P < 0.001). According to our research, patients with a lower risk profile may experience greater advantages from using a CTLA4 inhibitor, whereas patients with a higher risk profile demonstrated a higher level of responsiveness to Paclitaxel and Cisplatin. In addition, methotrexate exhibited a more positive outcome in patients with low risk compared to those with high risk. Conclusions: Our research introduces a novel model associated with OS gene signature in bladder cancer, which uncovers unique survival results. This model can assist in tailoring personalized treatment approaches and enhancing patient therapeutic effect in the management of bladder cancer

BIOCHEMICAL AND HISTOLOGICAL EVIDENCES FOR THE ANTITUMOR POTENTIAL OF TEUCRIUM OLIVERIANUM AND RHAZYA STRICTA IN CHEMICALLY-INDUCED HEPATOCELLULAR CARCINOMA

Background: Teucrium oliverianum and Rhazya stricta are medicinal plants used in traditional and herbal medicine for the treatment of diabetes, liver diseases and inflammatory conditions. The present study was planned to investigate the antitumor efficacy of Teucrium oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma (HCC) in rats. Materials and Methods: Forty adult male rats weighing 170-200 g were divided into four groups; each group was comprised of ten rats: (1): Normal healthy animals served as negative control group, (2): Hepatocellular carcinoma (HCC) group in which the rats were orally administered Nnitrosodiethylamine (dissolved in 0.9% normal saline), in a dose of 20 mg/kg b.wt. five times a week for six weeks, (3): HCC group treated with Teucrium oliverianum extract in a dose of 600 mg/kg b.wt for two months and (4): HCC group treated with Rhazya stricta extract in a dose of 750 mg/kg b.wt for two months. Serum alanine aminotransferase (ALT), asparatate aminotransferase (AST), alkaline phosphatase (ALP) and gammaglutamyl transferase (γ-GT) activities were estimated. Serum carcinoembyronic antigen (CEA), alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), glypican-3 (GPC-3), golgi protein 73 (Gp-73) and vascular endothelial growth factor (VEGF) levels were determined. Histopathological examination of liver tissue sections was also carried out. Results: The HCC group showed significant elevation in serum AST, ALT, ALP and γ-GT activities as well as CEA, AFP, AFU, Gpc-3, Gp 73 and VEGF levels versus the negative control group. Photomicrograph of liver tissue sections of rats in HCC revealed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of cystic cholangio carcinoma associated with areas of telangictasis with haemorrhage as well as individual hepatocellular necrosis. Conclusion: Treatment of HCC groups with Teucrium oliverianum or Rhazya stricta extract experienced significant improvement in the measured biochemical parameters as well as in the structural organization of the liver. In conclusion, the current study provided experimental evidences for the antitumor efficacy of Teucrium oliverianum and Rhazya stricta against hepatocellular carcinoma. Such effect could be attributed to hepatoprotective properties, antiproliferative activity and antiangiogenic potential

The impact of co-infections on fish: a review

International audienceAbstractCo-infections are very common in nature and occur when hosts are infected by two or more different pathogens either by simultaneous or secondary infections so that two or more infectious agents are active together in the same host. Co-infections have a fundamental effect and can alter the course and the severity of different fish diseases. However, co-infection effect has still received limited scrutiny in aquatic animals like fish and available data on this subject is still scarce. The susceptibility of fish to different pathogens could be changed during mixed infections causing the appearance of sudden fish outbreaks. In this review, we focus on the synergistic and antagonistic interactions occurring during co-infections by homologous or heterologous pathogens. We present a concise summary about the present knowledge regarding co-infections in fish. More research is needed to better understand the immune response of fish during mixed infections as these could have an important impact on the development of new strategies for disease control programs and vaccination in fish

Impact of <i>Chlorella vulgaris</i> Bioremediation and Selenium on Genotoxicity, Nephrotoxicity and Oxidative/Antioxidant Imbalance Induced by Polystyrene Nanoplastics in African Catfish (<i>Clarias gariepinus</i>)

Contamination of the environment with nano- and microplastic particles exerts a threatening impact on the aquatic ecosystems and sustainable catfish aquaculture. The presence of nanoplastics has been found to have a detrimental impact on both aquatic and terrestrial ecosystems. The present study examines the effect of polystyrene nanoplastics (PS NPs) on the DNA, erythrocytes, oxidative status and renal histology of catfish, in addition to the potential protective effects of Chlorella vulgaris bioremediation and selenium to hinder this effect. Six equal groups of fish were used as follows: Group 1 served as a control group and received water free from PS NPs; Group 2 was exposed to PS NPs at a concentration of 5 mg/L; Group 3 was exposed to PS NPs (5 mg/L) + selenium (1 mg/kg diet); Group 4 was exposed to PS NPs (5 mg/L) + C. vulgaris (25 g/kg diet); Group 5 was supplemented with C. vulgaris (25 g/kg diet); and Group 6 was supplemented with selenium (1 mg/kg diet). The exposure period was 30 days. The results indicated that PS NPs induced oxidative stress by significantly elevating malondialdehyde activities and slightly reducing antioxidant biomarkers, resulting in DNA damage, increased frequency of micronuclei, erythrocyte alterations, and numerous histopathological alterations in kidney tissue. Selenium and C. vulgaris significantly ameliorated the oxidative/antioxidant status, reducing DNA damage, micronucleus frequency, erythrocyte alterations, and improving the morphology of kidney tissue. Nevertheless, further research is needed for a profound understanding of the mechanism behind the toxicity of nano-microplatics in aquatic systems

Improvement effects of green tea and pumpkin oils on myelin oligodendrocyte glycoprotein-induced Multiple sclerosis in rats

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS) associated with significant progressive neurodegeneration. There is a lot of interest in the use of plant-based essential oils in traditional medicine to treat and prevent human illnesses, including MS. This research aimed to assess the neuroprotective effects of green tea oil (GTO) and pumpkin oil (PO) against myelin oligodendrocyte glycoprotein (MOG)-induced MS in Wistar rats as well as investigate the underlying molecular mechanisms. The Wistar rats were divided into four groups: group 1, normal control; group 2, MOG-injected; and groups 3 and 4, MOG-injected groups treated with 5 ml/kg body weight each of GTO and PO, respectively. The chemical profiles of components within a GTO and PO were identified using gas chromatography-mass spectrometry (GC–MS). Treatment with GTO and PO substantially improved the decreased dopamine, serotonin, norepinephrine, and acetylcholine levels in the brain of the MOG-injected rats. It also suppressed the elevated epinephrine levels. The histological injuries in the brain cortical tissue of the MOG-injected group were notably improved after supplementing with GTO and PO. Furthermore, brain lipid peroxidation and serum INF-β concentration were significantly lower in the MOG-injected rats treated with GTO and PO. The brain GSH, SOD, GPx, as well as serum coenzyme Q10, and α-tocopherol levels were significantly enhanced by GTO and PO supplementaion. Additionally, GTO and PO administration into MOG-injected rats significantly upregulated Nrf2, Bcl-2, and PCNA while significantly downregulated TNF-α, NF-κB, iNOS, p53, and Bax expression levels. Taken together, these findings suggest that GTO and PO efficiently ameliorate MOG-induced MS via enhancing the antioxidant, anti-inflammatory, and anti-apoptotic effects

Targeting the NF-κB p65/Bcl-2 signaling pathway in hepatic cellular carcinoma using radiation assisted synthesis of zinc nanoparticles coated with naturally isolated gallic acid

Purpose: Oral diethylnitrosamine (DEN) is a known hepatocarcinogen that damages the liver and causes cancer. DEN damages the liver through reactive oxygen species-mediated inflammation and biological process regulation. Materials and methods: Gallic acid-coated zinc oxide nanoparticles (Zn-GANPs) were made from zinc oxide (ZnO) synthesized by irradiation dose of 50 kGy utilizing a Co-60 γ-ray source chamber with a dose rate of 0.83 kGy/h and gallic acid from pomegranate peel. UV–visible (UV) spectrophotometry verified Zn-GANP synthesis. TEM, DLS, and FTIR were utilized to investigate ZnO-NPs' characteristics.Rats were orally exposed to DEN for 8 weeks at 20 mg/kg five times per week, followed by intraperitoneal injection of Zn-GANPs at 20 mg/kg for 5 weeks. Using oxidative stress, anti-inflammatory, liver function, histologic, apoptotic, and cell cycle parameters for evaluating Zn-GANPs treatment. Results: DEN exposure elevated inflammatory markers (AFP and NF-κB p65), transaminases (AST, ALT), γ-GT, globulin, and total bilirubin, with reduced protein and albumin levels. It also increased MDA levels, oxidative liver cell damage, and Bcl-2, while decreasing caspase-3 and antioxidants like GSH, and CAT. Zn-GANPs significantly mitigated these effects and lowered lipid peroxidation, AST, ALT, and γ-GT levels, significantly increased CAT and GSH levels (p<0.05). Zn-GANPs caused S and G2/M cell cycle arrest and G0/G1 apoptosis. These results were associated with higher caspase-3 levels and lower Bcl-2 and TGF-β1 levels. Zn-GANPs enhance and restore the histology and ultrastructure of the liver in DEN-induced rats. Conclusion: The data imply that Zn-GANPs may prevent and treat DEN-induced liver damage and carcinogenesis