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

Ultra-Processed Food Consumption and Relation with Diet Quality and Mediterranean Diet in Southern Italy

Ultra-processed food (UPF) consumption has been the focus of major attention due to their potential effects on human health. The aim of this study was to investigate the intake of UPFs in a sample of southern Italian individuals and assess its relationship with nutrient profile and dietary quality parameters. A cross-sectional study was conducted on 1936 individuals older than 18 years randomly selected from the general population. A total of 110 food times have been categorized based on the level of processing using the NOVA classification. The average daily energy intake of the sample was 2091.1 kcal, 38.7% of which were from the NOVA group of unprocessed/minimally processed foods, 5.7% from processed culinary ingredients, 38.3% from processed foods, and 17.9% from the UPFs group. UPFs were more consumed among young, unmarried individuals, with high cultural level, smokers, and often eating out of home. The mean energy share of UPFs varied from 6.3% of total daily energy intake for individuals in the lowest quintile of UPF consumption to 34.2% for those in the upper quintile. Within the UPF group, the highest energy contribution was provided by fast foods and sweets. Compared to the lowest quintile of UPF consumption, individuals in the highest quintile consumed, on average, additional 300 kcals per day and less fiber. Some plant-derived vitamins, such as vitamin A and vitamin C showed an inverse trend toward increasing shares of UPF consumption, while sodium intake increased. A significant higher intake of UPFs in individuals meeting the European and Italian dietary recommendations for carbohydrates, vitamin B12, vitamin D, and vitamin E was found, while UPFs were less consumed among those meeting the recommendations for total fats, fiber, sodium, potassium, and vitamin C. Finally, individuals displaying a &ldquo;healthier&rdquo; dietary profile, such as higher adherence to either the Mediterranean diet, the Dietary Approaches to Stop Hypertension, the Alternate Diet Quality Index, and the Diet Quality Index-International, consumed less UPFs and more unprocessed/minimally processed foods, with minor variation in the other NOVA food categories. In conclusion, consumption of UPF in southern Italy is in line with those reported in some other Mediterranean countries, although it negatively impacted the nutrient profile. It is important to monitor the consumption of UPFs before their availability and popularity put the grounds on younger generations&rsquo; dietary habits

Effect of Low-Carbohydrate Diet on Beta-Hydroxybutyrate Ketogenesis Metabolic Stimulation and Regulation of NLRP3 Ubiquitination in Obese Saudi Women

The effects of a ketogenic diet (KD) on anthropometric indices, the lipid profile, and the benefits of the ketone body beta-hydroxybutyrate (BHB) as an inhibitor of the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome in obese women were investigated in this study. From January to March 2021, 23 obese adult women (n = 23) with an average age of 35.30 years and BMI of 33.96 kg/m2 followed a KD. Instructions for the KD were given to eligible participants, with a typical plan and a menu for all the main meals, snacks, and drinks permitted over seven days. They were also free to change meals according to their preferences provided that they followed the plan. The participants attended six times throughout the intervention for measurements of their anthropometric indices, BHB levels, interleukin-1beta (1L-1&beta;) levels, and completion of a questionnaire (pre-intervention, mid-intervention, and post-intervention). Following the KD caused significant weight loss, a reduction in waist circumference and BHB levels, as well as a reduction in BMI and appetite. Cholesterol, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) increased slightly. However, low-density lipoprotein cholesterol (LDL-C) in serum increased significantly (p &lt; 0.05), and 1L-1&beta; decreased significantly (p &lt; 0.0001). The results show that the KD effectively encouraged weight loss and NLRP3 inflammasome inhibition. Based on the questionnaire results, it was found that a variety of physical symptoms, including overall energy, physical activity, mood, sleep, focus, skin conditions, and menstruation, had significantly improved

Polarity Directed Appraisal of Pharmacological Potential and HPLC-DAD Based Phytochemical Profiling of Polygonum glabrum Willd

The present study was designed to evaluate polarity-dependent extraction efficiency and pharmacological profiling of Polygonum glabrum Willd. Crude extracts of leaves, roots, stems, and seeds, prepared from solvents of varying polarities, were subjected to phytochemical, antioxidant, antibacterial, antifungal, antidiabetic, and cytotoxicity assays. Maximum extraction yield (20.0% w/w) was observed in the case of an acetone:methanol (AC:M) root extract. Distilled water:methanol (W:M) leaves extract showed maximum phenolic contents. Maximum flavonoid content and free radical scavenging potential were found in methanolic (M) seed extract. HPLC-DAD quantification displayed the manifestation of substantial quantities of quercetin, rutin, gallic acid, quercetin, catechin, and kaempferol in various extracts. The highest ascorbic acid equivalent total antioxidant capacity and reducing power potential was found in distilled water roots and W:M leaf extracts, respectively. Chloroform (C) seeds extract produced a maximum zone of inhibition against Salmonella typhimurium. Promising protein kinase inhibition and antifungal activity against Mucor sp. were demonstrated by C leaf extract. AC:M leaves extract exhibited significant cytotoxic capability against brine shrimp larvae and &alpha;-amylase inhibition. Present results suggest that the nature of pharmacological responses depends upon the polarity of extraction solvents and parts of the plant used. P. glabrum can be considered as a potential candidate for the isolation of bioactive compounds with profound therapeutic importance

Polarity directed appraisal of pharmacological potential and HPLC-DAD based phytochemical profiling of Polygonum glabrum Willd

The present study was designed to evaluate polarity-dependent extraction efficiency and pharmacological profiling of Polygonum glabrum Willd. Crude extracts of leaves, roots, stems, and seeds, prepared from solvents of varying polarities, were subjected to phytochemical, antioxidant, antibacterial, antifungal, antidiabetic, and cytotoxicity assays. Maximum extraction yield (20.0% w/w) was observed in the case of an acetone:methanol (AC:M) root extract. Distilled water:methanol (W:M) leaves extract showed maximum phenolic contents. Maximum flavonoid content and free radical scavenging potential were found in methanolic (M) seed extract. HPLC-DAD quantification displayed the manifestation of substantial quantities of quercetin, rutin, gallic acid, quercetin, catechin, and kaempferol in various extracts. The highest ascorbic acid equivalent total antioxidant capacity and reducing power potential was found in distilled water roots and W:M leaf extracts, respectively. Chloroform (C) seeds extract produced a maximum zone of inhibition against Salmonella typhimurium. Promising protein kinase inhibition and antifungal activity against Mucor sp. were demonstrated by C leaf extract. AC:M leaves extract exhibited significant cytotoxic capability against brine shrimp larvae and α-amylase inhibition. Present results suggest that the nature of pharmacological responses depends upon the polarity of extraction solvents and parts of the plant used. P. glabrum can be considered as a potential candidate for the isolation of bioactive compounds with profound therapeutic importance

Protective effects of green tea supplementation against lead-induced neurotoxicity in mice

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography–Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients

Developmental stages-specific response of anise plants to laser-induced growth, nutrients accumulation, and essential oil metabolism

Compared to seeds and mature tissues, sprouts are well known for their higher nutritive and biological values. Fruits of Pimpinella anisum (anise) are extensively consumed as food additives; however, the sprouting-induced changes in their nutritious metabolites are hardly studied. Herein, we investigated the bioactive metabolites, phytochemicals, and antioxidant properties of fruits, sprouts (9-day-old), and mature tissue (5-week-old) of anise under laser irradiation treatment (He-Ne laser, 632 nm). Laser treatment increased biomass accumulation of both anise sprouts and mature plants. Bioactive primary (e.g., proteins and sugars) and secondary metabolites (e.g., phenolic compounds), as well as mineral levels, were significantly enhanced by sprouting and/or laser light treatment. Meanwhile, laser light has improved the levels of essential oils and their related precursors (e.g., phenylalanine), as well as enzyme activities [e.g., O–methyltransferase and 3-Deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS)] in mature tissues. Moreover, laser light induced higher levels of antioxidant and anti-lipidemic activities in sprouts as compared to fruits and mature tissues. Particularly at the sprouting stage, anise was more responsive to laser light treatment than mature plants

Protective Effects of Green Tea Supplementation against Lead-Induced Neurotoxicity in Mice

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography&ndash;Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients

Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski&rsquo;s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood&ndash;brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-&kappa;B), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was &gt;20 &micro;g/mL as compared to cancer cells (Huh7.5; 17.32 &plusmn; 1.43 &micro;g/mL). Daturaolone significantly inhibited NF-&kappa;B and nitric oxide production with IC50 values of 1.2 &plusmn; 0.8 and 4.51 &plusmn; 0.92 &micro;g/mL, respectively. It significantly reduced inflammatory paw edema (81.73 &plusmn; 3.16%), heat-induced pain (89.47 &plusmn; 9.01% antinociception) and stress-induced depression (68 &plusmn; 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings