Background: The present study was conducted to evaluate the in vitro and in vivo antioxidant properties of aqueous extract of Podophyllum hexandrum. The antioxidant potential of the plant extract under in vitro situations was evaluated by using two separate methods, inhibition of superoxide radical and hydrogen peroxide radical. Carbon tetrachloride (CCl₄) is a well known toxicant and exposure to this chemical is known to induce oxidative stress and causes tissue damage by the formation of free radicals. Methods: 36 albino rats were divided into six groups of 6 animals each, all animals were allowed food and water ad libitum. Group I (control) was given olive oil, while the rest groups were injected intraperitoneally with a single dose of CCl₄ (1 ml/kg) as a 50% (v/v) solution in olive oil. Group II received CCl₄ only. Group III animals received vitamin E at a concentration of 50 mg/kg body weight and animals of groups IV, V and VI were given extract of Podophyllum hexandrum at concentration dose of 20, 30 and 50 mg/kg body weight. Antioxidant status in both kidney and lung tissues were estimated by determining the activities of antioxidative enzymes, glutathione reductase (GR), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and superoxide dismutase (SOD); as well as by determining the levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). In addition, superoxide and hydrogen peroxide radical scavenging activity of the extract was also determined. Results: Results showed that the extract possessed strong superoxide and hydrogen peroxide radical scavenging activity comparable to that of known antioxidant butylated hydroxy toluene (BHT). Our results also showed that CCl₄ caused a marked increase in TBARS levels whereas GSH, SOD, GR, GPX and GST levels were decreased in kidney and lung tissue homogenates of CCl₄ treated rats. Aqueous extract of Podophyllum hexandrum successfully prevented the alterations of these effects in the experimental animals. Conclusion: Our study demonstrated that the aqueous extract of Podophyllum hexandrum could protect the kidney and lung tissue against CCl₄ induced oxidative stress probably by increasing antioxidant defense activities.

Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats. Significant micronuclei induction and metaphase chromosome abnormalities in bone marrow cells exposed to three different DM doses (20, 40 and 60 mg/kg-bw) at multiple treatment durations (24, 48 and 72 h) indicated positive dose response relationship, confirming its genotoxic and cytotoxic potential. Significant mitotic index decrease was seen in dosed animals compared to vehicle control. The study used peripheral blood comet assay, indicating DM-mediated damage to DNA at all exposure levels in a time responsive manner. These assays were found to be an effective, precise, and fast technique with applied value in biomonitoring studies. Cell cycle and apoptosis along with mitochondrial membrane potential (MMP) in flow cytometric analyses confirmed DM exposure decreased MMP, affected the cell cycle, and inflicted DNA damage, which led to cellular apoptosis of leukocytes culminating into immunotoxic effects. The in silico experiments consequently augmented that DM showed acceptable binding energy value for Cyclin A2, suggesting that it could inhibit the cell cycle progression by inhibiting cyclin A2.

Macrophages, key players in the myeloid series, are vital for innate immunity, inflammation, pathogen elimination, host defense, and tissue repair. Their polarization can produce M1 and M2 phenotypes. At locations of tissue damage, M1 macrophages are triggered by TLR agonists or IFN-γ, leading to the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IFN-γ, and IL-12, as well as reactive oxygen species (ROS). In contrast, M2 macrophages that IL-4 and IL-13 have stimulated produce TGF-β, IL-6, and IL-10, which are anti-inflammatory cytokines. Additionally, these cells transform arginine into ornithine, which stimulates the production of collagen and cell division, which are essential for wound healing, neoangiogenesis, and tissue remodeling. The regulation of damage, inflammation, and tissue repair depends on macrophages’ capacity to dynamically alter their phenotype in response to external stimuli, including signals from pathogens, dying cells, and activated lymphocytes. M2 macrophages sustain tumor microenvironments, encourage endothelium development, and progress malignancy in neoplastic tissues. This chapter delves into the complex interplay of macrophage polarization, metabolism, and the advancement of illness. It emphasizes the molecular pathways, activation states, and potential therapeutic applications in conditions such as inflammation, cancer, cardiovascular diseases, and other afflictions.

PTEN loss activates PI3K–AKT signaling, and mTORC1 stimulates pyrimidine synthesis through S6K1-mediated CAD phosphorylation. This exploratory public-data analysis tested whether PTEN deletion in primary prostate cancer is associated with CAD, mTORC1 and pyrimidine-synthesis expression, and whether these survive protein-level and confounder analyses. In 485 primary tumors from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD; 159 PTEN-deleted), deletion was associated with higher CAD mRNA (Hedges’ g = 0.57) and higher Hallmark mTORC1 scores (g = 0.54). In 342 tumors with reverse-phase protein-array data, deletion was accompanied by lower PTEN protein and higher AKT Ser473 phosphorylation but not by a higher pre-specified mTORC1 phospho-output composite (g = −0.02), itself uncorrelated with the transcriptional score. In a pre-specified model adding purity, TP53, RB1, ERG fusion and batch (n = 276), the PTEN–CAD association was absent (β = −0.002; p = 0.96), whereas the mTORC1-score association persisted. In a post hoc decomposition, ERG fusion, which co-occurs with PTEN deletion (odds ratio 3.6), changed the coefficient most. Across eight cohorts, a small PTEN mRNA–CAD association (g = 0.23) was attenuated to 0.14 after ERG adjustment, with overlapping confidence intervals (Hartung–Knapp p = 0.071). Bulk-tumor pathway signatures and PTEN–CAD associations need protein-level and ERG-aware interpretation.