NLC containing Gefitinib (NANOGEF) was prepared using stearic acid, sesame oil and surfactants (sodium lauryl sulfate and tween 80). NANOGEFs were evaluated for particle size, polydispersity index (PdI), zeta potential, entrapment efficiency (EE), stability, release studies and cytotoxicity studies (MTT assay). The optimized NANOGEF exhibited particle size of 74.06 ± 9.73 d.nm, PdI of 0.339 ± 0.029 and EE of 99.76 ± 0.015%. The TEM study revealed spherical shape of NANOGEF formulations. The slow and sustained release behavior was exhibited by all NANOGEFs. The effects of surfactants were observed not only on particle size but also on zeta potential, entrapment efficiency, stability and release studies. The MTT assay revealed 4.5 times increase in cytotoxicity for optimized NANOGEF (IC 50 ¼ 4.642 mM) when compared with Gefitinib alone (IC 50 ¼ 20.88 mM in HCT-116 cells). Thus NANOGEF may be considered as a potential drug delivery system for the cure of colon cancer.
Obesity is a chronic metabolic disease identified by excessive fat deposition in the body with the highest risk of disordered lipid profile. Obesity and inappropriate lifestyles such as smoking and fake food not only influence blood lipids but also helps heavy metals and mineral be absorbed and adhered to the tissues with minimal disposal, that producing health problems with ages. A total of 49 female students (18-35 years old) included in this study to assess the relationship between body mass index, heavy metal, and minerals in university students. There is a strong correlation between BMI and potassium, where there is a positively weak relation between selected heavy metal and minerals and BMI. The increases in the presence of heavy metal and minerals in the present study not only depended in the BMI but also as a result of the rise in the effluent flow heavy metal from industrial units found in close nearness to rivers, oceans and seas have ended in an expansion in water bodies and seafood, fruits, vegetable crops and the food chain. That will need further investigation.
Introduction: Venetoclax (VCX) is a selective BCL-2 inhibitor approved for the treatment of leukemia and lymphoma. However, the mechanisms of anti-cancer effect of VCX either as a monotherapy or in combination with other chemotherapeutic agents against breast cancer need investigation. Methods: Breast cancer cell lines with different molecular subtypes (MDA-MB-231, MCF-7, and SKBR-3) were treated with different concentrations of VCX for indicated time points. The expression of cell proliferative, apoptotic, and autophagy genes was determined by qRT-PCR and Western blot analyses. In addition, the percentage of MDA-MB-231 cells underwent apoptosis, expressed higher oxidative stress levels, and the changes in the cell cycle phases were determined by flow cytometry. Results: Treatment of human breast cancer cells with increasing concentrations of VCX caused a significant decrease in cells growth and proliferation. This effect was associated with a significant increase in the percentage of apoptotic MDA-MB-231 cells and in the expression of the apoptotic genes, caspase 3, caspase 7, and BAX, with inhibition of antiapoptotic gene, BCL-2 levels. Induction of apoptosis by VCX treatment induced cell cycle arrest at G0/G1 phase with inhibition of cell proliferator genes, cyclin D1 and E2F1. Furthermore, VCX treatment increased the formation of reactive oxygen species and the expression level of autophagy markers, Beclin 1 and LC3-II. Importantly, these cellular changes by VCX increased the chemo-sensitivity of MDA-MB-231 cells to doxorubicin. Discussion: The present study explores the molecular mechanisms of VCX-mediated inhibitory effects on the growth and proliferation of TNBC MDA-MB-231 cells through the induction of apoptosis, cell cycle arrest, and autophagy. The study also explores the role of BCL-2 as a novel targeted therapy for breast cancer.
Lead (Pb) is recognized as the first heavy metal of the top six toxic air pollutants threatening human health and the second hazardous substance. Pb exposure is associated with lung impairment and high incidences of lung cancer. Nuclear factor kappa B (NF-jB) and aryl hydrocarbon receptor (AhR) signaling pathways are known to be expressed and play an important role in the lung. However, the link between Pb lung toxicity and NF-jB and/or AhR pathways remains unclear. This study was established to explore the role of NF-jB and AhR modulation in Pb-induced lung toxicity in human lung cancer A549 cells. In the current study, treatment of A549 cells with Pb significantly induced cell apoptosis as evidenced by increasing a) the percentage of cells underwent apoptosis determined by flow cytometry and b) p53 mRNA level. Pb treatment induced oxidative stress by a) increasing the formation of reactive oxygen species and b) decreasing GSTA1 mRNA levels. The toxic effects of Pb on the lung was associated with significant increases in NF-jB and AhR levels which was accompanied with increases in downstream targets genes, iNOS and CYP1A1, respectively. Inhibition of NF-jB or AhR either chemically using resveratrol or genetically using small interfering RNA (siRNA) significantly rescued A549 cells from Pb-mediated lung toxicity. The results clearly indicate that Pb-mediated lung toxicities are NF-jB and AhR-dependent mechanism.
Patients and Methods: This retrospective study was conducted among inpatients at Ministry of Health hospital in Jazan, a region in southwestern Saudi Arabia. We collected data for a 2-year period (from 2016 to 2017). For any detected DRP of the ordered medications for dispensing, the inpatient pharmacist is sending report for that particular DRP with recommendation to the medical team which in turn might accept or reject such recommendation. Serious drug-drug interactions, as part of DRP, were assessed by utilizing three different online DDI checkers, including Lexi-Comp, Medscape, and Drugs.com. Results: The most common type of DRP was serious drug-drug interactions (49%). Over the study period, most incidences of DRPs were decreased. Of the DRPs in 2016 and 2017, antibiotics were the most commonly involved (51% and 69.5%) of cases, respectively, followed by proton pump inhibitors (25.3% and 14.1%) and statins (12.9% and 9.4%). Interestingly, of the 241 interventions for DRPs in 2016, 199 (82.5%) were accepted, resulting in a change in drug therapy (p=0.006). In 2017, 90 (70.3%) interventions out of 128 were accepted by the physician and the drug therapy changed (p=0.029). Conclusion: Pharmacist interventions appear to decrease the incidence of DRPs, which emphasize the importance of an optimal pharmaceutical care plan for clinical care settings.
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