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.Keywords: Hepatocellular carcinoma, Teucrium oliverianum, Rhazya stricta, rat

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

Ameliorative Effects of Selenium and Chlorella vulgaris Against Polystyrene Nanoplastics-induced Hepatotoxicity in African Catfish (Clarias gariepinus)

Polystyrene nanoplastics pollution is a global issue that has grabbed the attention of scientists and drew widespread attention owing to the possible health risks it poses. The objective of this research was to investigate the hepatotoxic effects of polystyrene nanoplastics (PS NPs) in catfish (Clarias gariepinus) from the histopathological, biochemical, and ultrastructural profiles. Six groups of fish were used (n= 24/group): the first group kept as control, the second group exposed to 5mg/L NPs, the third group exposed to NPs+selenium (1mg/kg diet), the fourth group exposed to NPs+Chlorella (25g/kg diet), the fifth group received only Chlorella and the sixth group received only selenium. The exposure was for 30 days. The biochemical tests showed a rise in ALT and AST activities after exposure to NPs compared to control group. Groups exposed to NPs and supplemented with chlorella and selenium showed a significant decrease in the serum activities of these enzymes compared to NPs-intoxicated group. Results of histopathological examination demonstrated the hepatotoxic effects of NPs in NPs-intoxicated group that consisted of micro and macrovesciular steatosis, coagulative necrosis, pericentral fibrosis, periportal fibrosis, glycogen depletion and toxic changes in cellular ultrastructure. Chlorella and selenium supplementation alleviated the hepatotoxic effects of NPs and restored the histological and ultrastructural appearances of the liver tissue. Therefore, nanoplastics toxicity has well-defined hepatotoxic effects and these cytotoxic changes were mitigated by dietary supplementation of Chlorella and selenium

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