Dalia S. Morsi

Objective: The existing study sought to highlight the modulatory effect of co-treatment based on grape seed extract (GSE) and L. ascorbic acid (AA) on tumor microenvironment and immune response in murine solid Ehrlich carcinoma (SEC). Methods: GSE (200 mg / kg; orally) and AA (50 mg/ kg; orally) were given either separately or in a combination for 14 days. GSE active metabolites were identified using GC-MS and LC-MS/MS. Tumor size, Ki-67, Caspase-3, intratumoral infiltrated CD4+, CD8+ and FOXP3+ cells were detected immunohistochemically. Oxidative stress of tumor cells was determined. Serum levels of IL-12, IFN-γ, IL-4 and IL-10 were detected using ELISA. Results and discussion: The results revealed treatment with GSE and/or AA markedly diminished tumor size, intensified intratumoral oxidative stress, downregulated tumor cell proliferation along with upregulated tumor cells’ apoptosis. GSE and AA enhanced tumor immune microenvironment through increasing CD8+ and CD4+ T cells accompanied by decreasing FOXP3+ Treg cells infiltrated in tumors. GSE and/ or AA moved Th1/Th2 balance in favor of Th1 as evidenced by increased serum levels of IFN-γ and IL-12 accompanied with decreased serum levels of IL-4 and IL-10. These findings may be attributed to the presence of different chemical scaffolds of phenolic acids, Flavan-3-ols and its glycosides, glycerolipids and its glycosides, glycosylated seco-iridoids, dihydrochalcone, stilbenoid, flavone, dihydroxyflavone, and methylated flavone, sugars, and fatty acids. In conclusion, results suggested that dual treatment based on GSE & AA are promising anticancer therapeutics, through their potency to control proliferation, induce apoptosis, intratumoral oxidative stress, modulate tumor immune microenvironment and shifting Th1/Th2 response toward Th1

Wound healing is a complex natural process in which tissue requires recovering injured tissue cells. Helix aspersa has a high nutritional value and is considered a rich natural source of antioxidants and anti‐inflammatory agents. So, this study aimed to assess the effect of soft tissue crude extract and mucous of H. aspersa topically applied as a gel for 12 days. The wounds were observed and photographed twice a week. The inflammatory, oxidative stress markers and matrix metalloproteinases were evaluated in skin tissue homogenate and CD3⁺ and CD69⁺ T lymphocytes were detected in wound tissue. Data showed that a comparison of applying soft tissue crude extract and mucous of H. aspersa to skin wounds enhanced the healing process, resulting in a significant decrease in dermal inflammation compared to untreated mice. Also, they significantly increased the antioxidant enzyme activities with reduced malondialdehyde (MDA) levels in wound tissues. The levels of matrix metalloproteases‐2 and ‐9 were significantly decreased and the immune status was enhanced in the wound environment by increasing proportions of CD3⁺ and CD69⁺ T lymphocytes. H. aspersa mucous and soft tissue crude extract are viable substitutes for synthetic topical wound therapies with anti‐inflammatory, antioxidant, and immunomodulatory potencies, with a preference for the crude soft tissue extract based on the outcomes.

Florpyrauxifen‐benzyl (FPB) is a new arylpicolinate systemic herbicide that has been used to control or suppress the majority of herbicide‐resistant biotype weeds in rice. To our knowledge, the impact of FPB on the immune system remains undetected thus far. Hence, this work aimed to address the toxic effects of FPB and the possible related mechanisms on the spleen of exposed mice. Initially, an acute toxicological test was performed to ascertain the median lethal dose (LD₅₀) of FPB for 24 h which was found to be 371.54 mg/kg b.wt. For mechanistic evaluation of FPB toxicity, three sublethal doses (1/20^th, 1/10^th, and 1/5^th LD₅₀) were orally administered to mice for 21 consecutive days. Changes in spleen relative weight, oxidative status, apoptotic and inflammatory markers, histopathological alterations were evaluated. Following the FPB exposure, significant (p < 0.05) decline in spleen index, apoptotic features, histolopathological changes were observed. Additionally, excessive oxidative stress in spleen tissues was monitored by downregulating antioxidant enzymes and upregulating the oxidant parameters. Furthermore, exposure to FPB resulted in notable activation of the NF‐қB signaling pathway, accompanied by elevated levels of pro‐inflammatory cytokines (namely, IL‐1β and TNF‐α) as well as CD3 and CD19 levels have decreased significantly in spleen tissues. Collectively, FPB exposure exhibited apoptosis, oxidative stress, immunosuppression, and inflammatory response in a dose‐dependent manner, leading to spleen tissue damage and immunotoxicity. Further studies on FPB is recommended to outstand its hazards on ecosystems.

A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC₅₀ values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers’ (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.