Ehrlich ascites carcinoma provokes renal toxicity and DNA injury in mice: Therapeutic impact of chitosan and maitake nanoparticles.

In this study, the impact of chitosan (CS) and maitake (GF) nanoparticles towards the renal toxicity induced by Ehrlich ascites carcinoma (EAC) in vivo model was conducted. Besides benchmark negative control group, EAC model was constructed by intraperitoneal injection (i.p.) of 2.5 × 106 cells. Alongside positive control, two groups of EAC-bearing mice received 100 mg/kg of CS and GF nanoparticles/body weight daily for 14 days. The kidney function was conducted by measuring urea, creatinine, ions, (anti)/oxidative parameters and DNA damage. Also, measuring immunoreactivity of P53, proliferating cell nuclear antigen (PCNA), and B-cell lymphoma 2 (Bcl-2) and apoptosis protein. The outcomes illustrated notable kidney toxicity, which indicated by elevations in urea, creatinine, oxidative stress, DNA damage and induction of apoptosis. These events were supported by the drastic alteration in kidney structure through histological examination. Administration of CS and GF nanoparticles was able to enhance the antioxidant power, which further reduced oxidative damage, DNA injury, and apoptosis. These results indicated the protective and therapeutic role of biogenic chitosan and maitake nanoparticles against nephrotoxicity.

Combined effects of naringin and doxorubicin on the JAK/STAT signaling pathway reduce the development and spread of breast cancer cells.

Breast cancer therapy options are limited due to its late diagnosis and poor prognosis. Doxorubicin is the fundamental therapy approach for this disease. Because chemotherapy has numerous adverse effects, the scope of the existing research was to appraise the synergetic effect of doxorubicin and naringin and explore the underlying mechanism. The cytotoxicity of doxorubicin and naringin on MCF-7 was monitored. Furthermore, the expression of STAT3 and JAK1 as well as the apoptotic and metastatic related genes (Bax, Bcl-2, Survivin, and VEGF) were conducted by immunoblotting assay and qRT-PCR. In addition, a wound healing test was utilized to appraise the migration and metastasis of MCF-7. Our results revealed that naringin and doxorubicin had a synergetic inhibitory influence on MCF-7 cells growth and migration. The synergetic action of doxorubicin and naringin effectively hindered the expression of STAT3, JAK1, Bcl-2, Survivin, and VEGF, with a boost in the level of Bax compared to cells treated with either doxorubicin or naringin. In conclusion, our findings imply that combining doxorubicin with naringin may be a favorable strategy for inhibiting the growth of breast cancer.

Alzheimer's disease-related brain insulin resistance and the prospective therapeutic impact of metformin.

Besides COVID-19, two of the most critical outbreaks of our day are insulin resistance, type 2 diabetes mellitus (T2DM), and Alzheimer's disease (AD). Each disease's pathophysiology is well established. Furthermore, a substantial overlap between them has coexisted. Uncertainty remains on whether T2DM and AD are parallel illnesses with the same origin or separate illnesses linked through violent pathways. The current study was aimed at testing whether the insulin resistance in the brain results in AD symptoms or not. Insulin resistance was induced in the brains of rats using a single intracerebroventricular streptozotocin (STZ) dose. We then measured glucose, insulin receptor substrate 2 (IRS-2), amyloid ß (Aß) deposition, and tau phosphorylation in the brain to look for signs of insulin resistance and AD. The results of this study indicated that a single dose of STZ was able to induce insulin resistance in the brain and significantly decline IRS-2. This resistance was accompanied by obvious memory loss, Aß deposition, and tau phosphorylation, further visible diminishing in neurotransmitters such as dopamine and acetylcholine. Furthermore, oxidative stress was increased due to the antioxidant system being compromised. Interestingly, the pancreas injury and peripheral insulin resistance coexisted with brain insulin resistance. Indeed, the antidiabetic metformin was able to enhance all these drastic effects. In conclusion, brain insulin resistance could lead to AD and vice versa. These are highly linked syndromes that could influence peripheral organs. Further studies are required to stabilize this putative pathobiology relationship between them.

Synthesis, Characterization, and Anticancer Potency of Branched Poly (p-Hydroxy Styrene) Schiff-Bases.

A significant issue in cancer biology is finding anticancer therapies that effectively kill cancer cells. Through the use of several aldehydes, Schiff bases based on branched poly (p-hydroxy styrene) are created. The branched polymer is first chloroacetylated, then aminated with 1,4-phenylenediamine, and finally, aldehydes are reacted with the aminated polymer to produce the Schiff base compounds. Through the utilization of FTIR, TGA, XRD, NMR, and elemental analysis, all synthesized Schiff-bases are identified and characterized. Further, the antineoplastic potential of all Schiff bases is evaluated against different cancer cell lines. The results gained from this study indicate that the Schiff base polymers have cytotoxic power against cancer cells depending on cancer cell type and this antiproliferation potency is dose-concentration dependent. Importantly, the prepared S1 Schiff-base polymer shows potent cytotoxicity and is able to trigger the apoptosis and reactive oxygen species (ROS) in MCF-7 cells. Further, it downregulates VEGFR protein expression. The Schiff base polymers would have extensive applications in the biological disciplines.

Functional Assembly of Caenorhabditis elegans Cytochrome b-2 (Cecytb-2) into Phospholipid Bilayer Nanodisc with Enhanced Iron Reductase Activity.

Among seven homologs of cytochrome b561 in a model organism C. elegans, Cecytb-2 was confirmed to be expressed in digestive organs and was considered as a homolog of human Dcytb functioning as a ferric reductase. Cecytb-2 protein was expressed in Pichia pastoris cells, purified, and reconstituted into a phospholipid bilayer nanodisc. The reconstituted Cecytb-2 in nanodisc environments was extremely stable and more reducible with ascorbate than in a detergent-micelle state. We confirmed the ferric reductase activity of Cecytb-2 by analyzing the oxidation of ferrous heme upon addition of ferric substrate under anaerobic conditions, where clear and saturable dependencies on the substrate concentrations following the Michaelis-Menten equation were observed. Further, we confirmed that the ferric substrate was converted to a ferrous state by using a nitroso-PSAP assay. Importantly, we observed that the ferric reductase activity of Cecytb-2 became enhanced in the phospholipid bilayer nanodisc.

Osthole extracted from a citrus fruit that affects apoptosis on A549 cell line by histone deacetylasese inhibition (HDACs).

This study aims to investigate the interactions between osthole extracted from Egyptian citrus fruits as HDACs inhibitor by theoretical study and practically. Besides, osthole was assed as anti-cancer activity. In this study, osthole was extracted from the Egyptian citrus fruit and was characterized. The role of osthole as in vitro inhibitor of HDACs was estimated and evaluated the antitumor activity against human lung cancer cells (A549), Caspase-9 activity was detected. The results obtained from GC-MS indicate that the grapefruit showed the highest osthole concentration compared to the other citrus fruits. Moreover, the grapefruit osthole competitively inhibits HDACs. The inhibition constant value, (Ki=3.36 mM), indicates that osthole exerts an inhibitory effect upon HDACs activity. In vitro study of osthole could inhibit the growth of A549 cells that depend on time and concentration. It also induces apoptosis and causes an increase of caspase-9 by osthole. In conclusion, grapefruit osthole could induce the apoptosis in A549 lung cancer cells by inhibiting the histone deacetylase.