Nanocarriers for anticancer drugs: Challenges and perspectives

Cancer is the second most common cause of death globally, surpassed only by cardiovascular disease. One of the hallmarks of cancer is uncontrolled cell division and resistance to cell death. Multiple approaches have been developed to tackle this disease, including surgery, radiotherapy and chemotherapy. Although chemotherapy is used primarily to control cell division and induce cell death, some cancer cells are able to resist apoptosis and develop tolerance to these drugs. The side effects of chemotherapy are often overwhelming, and patients can experience more adverse effects than benefits. Furthermore, the bioavailability and stability of drugs used for chemotherapy are crucial issues that must be addressed, and there is therefore a high demand for a reliable delivery system that ensures fast and accurate targeting of treatment. In this review, we discuss the different types of nanocarriers, their properties and recent advances in formulations, with respect to relevant advantages and disadvantages of each.     

Design,synthesis and molecular docking of new fused 1H-pyrroles,pyrrolo[3,2-d]pyrimidines and pyrrolo[3,2-e][1, 4]diazepine derivatives as potent EGFR/CDK2 inhibitors

A new series of 1H-pyrrole (6a–c, 8a–c), pyrrolo[3,2-d]pyrimidines (9a–c) and pyrrolo[3,2-e][1, 4]diazepines (11a–c) were designed and synthesised. These compounds were designed to have the essential pharmacophoric features of EGFR Inhibitors, they have shown anticancer activities against HCT116, MCF-7 and Hep3B cancer cells with IC₅₀ values ranging from 0.009 to 2.195 µM. IC₅₀ value of doxorubicin is 0.008 µM, compounds 9a and 9c showed IC₅₀ values of 0.011 and 0.009 µM respectively against HCT-116 cells. Compound 8b exerted broad-spectrum activity against all tested cell lines with an IC₅₀ value less than 0.05 µM. Compound 8b was evaluated against a panel of kinases. This compound potently inhibited CDK2/Cyclin A1, DYRK3 and GSK3 alpha kinases with 10–23% compared to imatinib (1–10%). It has also arrested the cell cycle of MCF-7 cells at the S phase. Its antiproliferative activity was further augmented by molecular docking into the active sites of EGFR and CDK2 cyclin A1.     

Green sensitive spectrofluorimetric determination of pemetrexed as antineoplastic drug: Application in pharmaceutical dosage forms and spiked human plasma

A recent antineoplastic medication is pemetrexed, this medicine is now being developed and produced on a large scale, thus approaches for quality control are urgently needed. Spectrofluorimetric guidelines for the simple estimation of pemetrexed were validated. Pemetrexed's assay depends on observations of its native fluorescence at wavelengths 275/450 nm and pH 4. The proposed approach was also used to identify the examined drug in both its formulation and in human plasma that had been spiked.     

Bioaccumulation Potential and Physiological Responses of Aquatic Macrophytes to Pb Pollution

In view of their potential bioaccumulation of heavy metals, Ceratophyllum demersum and Myriophyllum spicatum was studied under hydroponic cultures enriched by different Pb concentrations (25, 50, 75 mg/l) for 1–7 days. Both species exerted remarkable capabilities to concentrate Pb in their tissues as compared to control. The highest accumulation value of Pb (164.26 mg/g.dw) was recorded in C. demersum and the most of metal (91.72 mg/g dw) accumulated after 1 d. Significant reduction in photosynthetic pigments and appearance of morphological symptoms such as chlorosis and fragmentation of leaves were evident after 7d at 75 mg/l. The activity of POX and APX, carotenoids and proline showed induction at lower concentration and duration followed by decline. Major re-shuffle in protein patterns appeared as a tolerant mechanism, which both species developed under Pb toxicity. Results suggest that both species responded positively to Pb concentration and accumulated high amount of metal. Due to metal accumulation coupled with detoxification potential, both species appear to have potential for use as phytoremediators and the developed responses can be used as reliable biomarkers for Pb water pollution.     

Optimum growth conditions for Amphidinium carterae Hulburt from eutrophic waters in Alexandria (Egypt) and its toxicity to the brine shrimp Artemia salina

Cultures of a strain of Amphidinium carterae Hulburt isolated from a eutrophic basin in Alexandria were investigated for the optimum growth conditions, including vitamin requirements, the assimilation index and the potential toxicity of this species. A division rate of 2.7 day^–1, was reached on the second and third day under optimum conditions, with and without addition of B₁₂ and biotin. The rate of C₁₄ assimilation per unit chlorophyll ranged from 0.2 to 5.4 mgC.(mg Chla)-1.h^–1 according to the growth conditions and to cell size. As the cell density increased in the cultures, the cell size decreased and their photosynthetic efficiency increased. Toxicity of A. carterae to brine shrimp resulted from grazing and not from membrane diffusion of extracellular toxins.     

3D-Pharmacophore Modeling,Molecular Docking,and Virtual Screening for Discovery of Novel CDK4/6 Selective Inhibitors

Russian Journal of Bioorganic Chemistry - Structure-based pharmacophore mapping, drug-likeness and ADMET profiles were used as tools in our virtual screening process, in addition to molecular...     

Evaluation of mRNA expression level of the ATP synthase membrane subunit c locus 1 (ATP5G1) gene in patients with schizophrenia

BackgroundSchizophrenia is a serious, complex mental disorder. The impairment of oxidative phosphorylation has a detrimental consequence on CNS function. Different ATP synthase subunits have been involved in the pathological process of various neurodegenerative disorders. Our goal was to evaluate the mRNA expression level of the ATP synthase membrane subunit c locus 1 (ATP5G1, also named ATP5MC1) gene in patients with schizophrenia.MethodsDetermination of the expression levels of ATP5G1 in plasma and peripheral blood mononuclear cells (PBMCs) were performed by real-time PCR in 90 controls and 90 patients with schizophrenia.ResultsPatients had significantly decreased ATP5G1 mRNA expression levels in both plasma and PBMCs compared to controls. The receiver operating characteristic curve was applied to detect a cut-off value of ATP5G1 expression in plasma and PBMCs. The ATP5G1 relative expression in PBMCs had better performance with a cut-off value ≤ 21 (AUC = 0.892, P < 0.001), sensitivity of 94.44%, and specificity of 72.22% in discriminating between schizophrenic patients. ATP5G1 expression in PBMCs was an independent predictor in schizophrenia.ConclusionThis study revealed a down-regulation of ATP5G1 expression in schizophrenia, precisely expression in PBMCs. That might give insight into the role of ATP5G1 gene in the pathogenesis of schizophrenia.     

Impact of melatonin and tryptophan on water stress tolerance in white lupine (Lupinus termis L.)

Melatonin  has been identified as a signal molecule that regulates plant responses to different abiotic and biotic stresses. Melatonin (MT) and its precursor tryptophan (Try) have a major role in improving plant stress tolerance to different environmental stresses such as water deficiency. The rapid increase in the Egyptian population caused insufficient protein sources, especially those of animal origin, in their diet. The possible solution is to augment the diet with legumes such as white lupine which are relatively rich in protein. Thus, the current experimental work was carried out to find changes in growth, biochemical aspects and yield quantity and quality of white lupine plant with spraying of both MT and Try at different concentrations on plant shoot under water deficit stress conditions. Results showed that water deficit (75 or 50% of water irrigation requirements; WIR) caused significant reduction in growth, photosynthetic pigments, indole acetic acid and yield compared with those received 100% WIR. Seed yield significantly decreased (p < 0.05) by 26.98 and 41.64% by decreasing WIR to 75 and 50%. The decrease was accompanied by significant increase in phenolic contents, hydrogen peroxide, lipid peroxidation and some antioxidant enzymes, while nitrate reductase enzyme was decreased. However, external application of either MT or Try significantly alleviated the adverse effects of water deficit (growth suppression), since MT or Try-treated plants recovered more quickly than untreated plants. Moreover, MT or Try—treated plants had higher photosynthetic pigments, indole acetic acid, phenolic, as well as yield quantity and quality under the three WIR as compared with untreated plants. Melatonin treatment at 100 µM and Tryptophan at 200 µM increased weight of seeds/plant by 78.29 and 52.19%, 71.49 and 43.78% and 41.21 and 13.07% in plants irrigated with 100, 75 and 50% WIR, respectively. Exogenous MT and Try significantly reduced hydrogen peroxide and malondialdehyde content, while markedly increased the activities of antioxidant enzymes and nitrate reductase under different WIR. Finally, the current study concluded that MT and Try treatments alleviated the detrimental effects of water deficiency and accelerated the recovery mainly via improving white lupine plants tolerance in forms of enhancing photosynthetic pigments, indole acetic acid, phenolic and antioxidant capacity.     

Association of ghrelin and leptin with reproductive hormones in constitutional delay of growth and puberty

Background  

Constitutional delay of growth and puberty (CDGP) is a variation of the onset and timing of pubertal development without a defined endocrine abnormality. Recently published studies indicate that leptin and ghrelin play a role in puberty initiation and progress. They have been implicated in regulation of GnRH secretion, with ghrelin having inhibitory and leptin, facilitatory effects. We hypothesized that elevated ghrelin and reduced leptin concentrations could be implicated in altering the tempo of puberty in adolescents with CDGP. So in the current study we evaluate variations in leptin and ghrelin levels in adolescent boys with CDGP, the relationships between both hormones and reproductive hormones including LH, FSH and testosterone were also evaluated.