Oxidative stress and DNA damage in relation to transition metals overload in Abu-Qir Bay,Egypt

The aim of the present study is to evaluate the transition metals overload in Abu-Qir Bay in Egypt, as compared to a less polluted area (reference area) through some biomarkers of oxidative stress. Catalase enzyme activity, malondialdehyde (MDA) concentration and DNA damage (number of apurinic/apyrimidinic sites) were the tested biomarkers. The levels of iron and copper in Mugil cephalus liver tissues were significantly higher in samples from the polluted area as compared to the reference area: Fe: 407 ± 38 vs. 216 ± 21 μg/g wet wt; p = 0.008, Cu: 54 ± 6 vs. 17.7 ± 4 μg/g wet wt; p = 0.0001. This could account for the observed increase in MDA concentration (15.7 ± 5.7 vs. 2.5 ± 0.5 U/g; p = 0.035), and the elevated number of AP sites (13.9 ± 2.6 vs. 0.37 ± 0.2 AP site/1 × 10⁵ bp; p = 0.0001). Similarly, the activity of catalase enzyme responsible for the cellular defense was significantly high (58.3 ± 12.2 vs. 28.4 ± 4.0 U/mg; p = 0.032). The present data indicated a clear relationship between the pollution degree of the above marine environment and both biochemical and molecular responses of the piscine system.     

Effects of Silver Nanoparticles on Burn Wound Healing in a Mouse Model

Biological Trace Element Research - Healing of injuries caused by exposure to heat has been discussed in many studies, although a few drugs have been shown to produce satisfactory results. In this...     

Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase

Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in fatty acid and energy metabolism, but little is known about its nutritional regulation. Dietary methionine restriction in rats decreases hepatic Scd1 mRNA and protein, increases energy expenditure, and decreases fat-pad mass/body-weight% (FM/BW%). In humans, plasma concentrations of the methionine product, cysteine, are associated with obesity. To determine which consequences of methionine-restriction are mediated by decreased cysteine availability, we monitored obesity-related variables in 4 dietary groups for 12 weeks: control-fed (CF), methionine-restricted (MR), MR supplemented with 0.5% l-cysteine (MR+Cys) and CF+Cys rats. MR lowered weight gain and FM/BW% despite higher food intake/weight than CF, and lowered serum cysteine. Hepatic Scd1 expression was decreased, with decreased serum SCD1 activity indices (calculated from serum fatty acid profile), decreased serum insulin, leptin and triglycerides, and higher adiponectin. Cysteine supplementation (MR+Cys) essentially reversed all these phenotypes and raised serum cysteine but not methionine to CF levels. Adding extra cysteine to control diet (CF+Cys) increased serum taurine but did not affect serum cysteine, lipids, proteins, or total weight gain. FM/BW% and serum leptin were modestly decreased. Our results indicate that anti-obesity effects of MR are caused by low cysteine and that dietary sulfur amino acid composition contributes to SCD1 regulation.     

Design,synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M

A new class of EGFR PROTACs based on pomalidomide was developed, synthesised, and tested for their cytotoxic activity against a panel of human cancer cells. Compounds 15–21 were showed to be more effective against the four tested cell lines than erlotinib. In particular, compound 16 was found to be the most potent counterpart as it was 5.55, 4.34, 5.04, and 7.18 times more active than erlotinib against MCF-7, HepG-2, HCT-116, and A549 cells, respectively. Compound 15 was revealed to be more active than doxorubicin against the four tested cell lines. Furthermore, the most potent cytotoxic compounds were studied further for their kinase inhibitory effects against EGFR^WT and EGFR^T790M using HTRF test. Compound 16 showed to be the most effective against both kinds of EGFR, with IC₅₀ values of 0.10 and 4.02 µM, respectively. Compound 16 could effectively degrade EGFR protein through ubiquitination (D_max = 96%) at 72 h in the tested cells.     

Cyanidin-3-Glucoside Modulates hsa_circ_0001345/miRNA106b/ATG16L1 Axis Expression as a Potential Protective Mechanism against Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common form of malignancy in the liver. Autophagy was found to have a significant effect in controlling HCC. Anthocyanins, which are naturally occurring pigments in a variety of fruits and vegetables, have been thoroughly documented to be involved in a variety of bioactive activities and are widely employed for their antioxidant capabilities. Cyanidin-3-glucoside (C3G) extracted from Morus alba L. has promising antioxidant and anti-tumour activities. The current study aims to examine the protective action of C3G against hepatocellular carcinoma through the investigation of the autophagy protein ATG16L1 expression along with its related RNA molecules (hsa_circ_0001345 and miRNA106b) in Wistar rats. In vivo precancerous lesions (PCL) were induced using diethylnitrosamine (DEN) and acetamidofluorene (2-AAF). Rats were treated with C3G (10, 15, and 20 mg/kg; 4 times weekly) for 112 days (16 weeks). Liver function tests, alfa fetoprotein, ATG16L1 expression, hsa_circ_0001345, and miRNA106b differential expression were examined. Liver sections were examined by histological and immunohistochemical approaches. The current study’s findings indicated that C3G administration protects against the negative effects of DEN-2-AAF on liver functions and liver histopathological sections, which nominated C3G as a potential prophylactic agent against HCC.     

Micelle‐enhanced spectrofluorimetric method for quantification of entacapone in tablets and human plasma

In this paper, a simple and highly sensitive spectrofluorimetric method was developed and validated for the determination of entacapone (ETC). The proposed method is based on forming a highly fluorescent product through the reduction of ETC with Zn/HCl. The produced fluorophore exhibits strong fluorescence at λ_em 345 nm after excitation at λ_ex 240 nm. The use of fluorescence enhancers such as Tween‐80 and carboxy methyl cellulose (CMC) greatly enhanced the fluorescence of the produced fluorophore by 150% and 200%, respectively. Calibration curves showed good linear regression (r2 > 0.9998) within test ranges of 0.05–2.0 and 0.02–1.80 μg mL^?1 with lower detection limits of 1.27 × 10^?2 and 4.8 × 10^?3 μg mL^?1 and lower quantification limits of 4.21 × 10^?2 and 1.61 × 10^?2 μg mL^?1 upon using Tween‐80 and or CMC, respectively. The method was successfully applied to the analysis of ETC in its pharmaceutical formulations (either alone or in presence of other co‐formulated drugs). The results were in good agreement with those obtained using the official method. The methods were further extended to determine the drug in human plasma samples, and to study the pharmacokinetics of ETC. The paper is the first report on the spectrofluorimetric determination of entacapone.     

Chemical Composition of Aqueous Ethanol Extract of Luffa cylindrica Leaves and Its Effect on Representation of Caspase‐8, Caspase‐3, and the Proliferation Marker Ki67 in Intrinsic Molecular Subtypes of Breast Cancer in Vitro

Breast cancer constitutes the second most prevalent cancer in Egypt, the problem needs more trends in treatment and treatment development either by regimen modification or introducing new drugs, and the main objective of this study is to screen the effects of the aqueous ethanol herbal extract of Luffa cylindrica leaves on different types of breast cancer cell lines representing different molecular subtypes of the disease. The major active constituents of the extract were tentatively identified by LC/MS which revealed the presence of phenolic compound derivatives and saponin that may be responsible in part for the activity of the extract. The emphasis was laid on the main apoptotic pathways as well as the extract effect on the normal cell line. Results of phytochemical investigation, cell cycle analysis, and molecular analysis of apoptotic and proliferative markers have shown effective anticancer activity against MCF‐7, BT‐474, and MDA‐MB‐231 cell lines which represent three subtypes of breast cancer, luminal A, luminal B, and triple negative, respectively. On the other hand, the effects on normal lung fibroblast cell line are less prominent at the dose used for treating breast cancer cell lines.