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Fluorine containing Hexahydroquinoline-3-carbonitrile derivatives were found to have potent cytotoxicity. Further, Fluorine can modulate pharmacokinetic and pharmacodynamic profile of drugs. Hence, new derivatives containing fluorine were explored as potential cytotoxic agents.

Difluoro substituted compounds containing aromatic/heteroaromatic rings were designed, synthesized and screened for in vitro cytotoxicity on cancer cell lines. The active compounds were subjected to docking on Mcl-1 and ADME/T prediction.

The synthesized compounds were characterized using various spectral techniques like FT-IR, 1 H NMR, 13C NMR and Mass spectra. Compounds were screened for cytotoxicity on NCI-60 cell lines at National Cancer Institute. click here The active compounds were evaluated additionally by MTT and SRB assay.

Compounds (6l and 6o) showed maximum cytotoxicity with (% GI) of 69 and 63.7 at 10 µM drug concentration respectively. Compound 6i showed potent cytotoxicity with GI50 of 7.2 µM against Ishikawa cell line. Compound 6o was nearly as active as reference with IC50 of 9.39 µM and 13.54 µM against HT-29 and HCT-116 respectively and compound 6l also showed equal potency to that of reference with IC50 of 9.66 µM against Caco-2. Compounds 6i, 6o and 6l showed high docking score suggesting their cytotoxicity. Further, ADME/T prediction revealed that all the compounds have drug likeness properties.

Enhanced lipophilic interaction of compounds due to presence of fluorine in compounds 6i and 6l was revealed during docking study. Compound 6i can be explored as a lead molecule against other endometrial cancer in futuristic drug development.

Enhanced lipophilic interaction of compounds due to presence of fluorine in compounds 6i and 6l was revealed during docking study. Compound 6i can be explored as a lead molecule against other endometrial cancer in futuristic drug development.Head and neck squamous cell carcinoma (HNSCC) continues to be a global public health burden even after a tremendous development in its treatment. It is a heterogeneous cancer of upper aero-digestive tract . The contemporary strategy to treat cancer is the use of anticancer drugs against proteins possessing abnormal expression. Targeted chemotherapy was found successful in HNSCC but still, there is a stagnant improvement in the survival rates and high recurrence rates due to undesirable chemotherapy reactions, non-specificity of drugs, resistance against drugs and drug toxicity on non-cancerous tissues and cells. Various extensive studies lead to the identification of drug targets capable to treat HNSCC effectively. The current review article gives an insight into these promising anticancer targets along with knowledge of drugs under various phases of development. In addition, new potential targets that are not yet explored against HNSCC are also described. We believe that exploring and developing drugs against these targets might prove beneficial in treating HNSCC.

Despite the effect of education and APOE ε4 allele on amyloid-beta (Aβ) retention and memory, previous studies have not dealt with an interaction between two factors on Aβ deposition and memory function in the course of Alzheimer's disease (AD).

To evaluate education by APOE ε4 allele interactions for Aβ retention and neuropsychological test scores in cognitively normal older adults without Aβ deposition [CN(Aβ-), n=45] and Alzheimer's disease patients with Aβ retention [AD(Aβ+), n=33].

Multiple regression analyses (adjusted for age, gender) were conducted to examine the effects of education, APOE ε4 allele, and the interaction between the two factors on global, regional Aβ load quantified using [18F]flutemetamol standardized uptake value ratio with the pons as a reference region, and on neuropsychological test scores in each group.

The interaction between education and APOE ε4 allele had an effect on amyloid load in parietal lobes (uncorrected p<0.05) and striatum (Bonferroni corrected p<0.05) in each CN(Aβ-) and AD(Aβ+). There was also an interaction effect of education and APOE ε4 allele on the memory performance in each CN(Aβ-) and AD(Aβ+) (uncorrected p<0.05). APOE ε4 carriers of both groups showed opposing slopes with each other in the correlation between the education years and Aβ load, memory performance.

The current results suggest a possible explanation of the differential effects of education and APOE ε4 allele interactions on AD pathology and memory function at the beginning and end of AD progress. However, further study with a validating cohort is needed for confirming this explanation.

The current results suggest a possible explanation of the differential effects of education and APOE ε4 allele interactions on AD pathology and memory function at the beginning and end of AD progress. However, further study with a validating cohort is needed for confirming this explanation.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive respiratory disease characterized by the destruction of the alveolar structure. In pulmonary fibrosis, aerosolized drugs are easily transferred to the systemic circulation via leakage through the injured alveolar epithelium. Therefore, pulmonary drug delivery systems for sustained distribution in fibrotic lungs are needed.

We evaluated the intrapulmonary pharmacokinetics of aerosolized liposomes as pulmonary drug delivery systems in mice with bleomycin-induced pulmonary fibrosis.

The aerosolized liposomal formulations and solutions of model compounds, including indocyanine green and 6- carboxyfluorescein (6-CF), were intrapulmonarily administered to mice with bleomycin-induced pulmonary fibrosis. In vivo imaging for indocyanine green and 6-CF measurements in lung tissues and plasma were performed. Additionally, in vitro permeation experiments using NCI-H441 cell monolayers as a model of alveolar epithelial cells were performed.

The fluorr the sustained distribution of antifibrotic agents in fibrotic lungs and the optimization of IPF therapy.

The purpose of this study was to explore the mechanism of the miR-375/XPR1 axis in esophageal squamous cell carcinoma (ESCC) and provide a new idea for targeted therapy of ESCC.

Differentially expressed genes in GEO and TCGA databases were analyzed by bioinformatics. The expression levels of miR-375 and XPR1 mRNA were detected by qRT-PCR. Protein expression of XPR1 was detected by western blot. Bioinformatics analysis and dual luciferase assay were conducted to confirm the targeting relationship between miR-375 and XPR1. The viability, proliferation, migration and invasion of cells in each treatment group were detected by CCK-8, colony formation, wound healing and Transwell assays.

Significantly down-regulated miR-375 and remarkably up-regulated XPR1 were observed in ESCC tissue and cells. Overexpression of miR-375 inhibited proliferation, invasion and migration of ESCC cells, and greatly reduced the promoting effect of XPR1 overexpression on cell proliferation, migration and invasion. Dual luciferase assay confirmed that miR-375 targeted and inhibited XPR1 expression in ESCC.