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The hydrolysis rate of TAF is affected by pH and water content in the implant microenvironment. We further demonstrate the ability to substantially delay the degradation of TAF by reducing the rates of drug release and thus lowering the water ingress rate. Using this approach, we achieved sustained release of TAFFB formulations over 240 days and maintained > 93% TAF purity under simulated physiological conditions. The opportunities for optimization of TAF formulations in this biodegradable implant supports further advancement of strategies to address long-acting HIV PrEP.Gastrointestinal cancers (GI) account for 26% of cancer incidences globally and 35% of all cancer-related deaths. The main challenge is to target cancer specific antigens. Mucins are heavily O-glycosylated proteins overexpressed in different cancers. The transmembrane glycoprotein MUC1 is the most likeable target for antibodies, owing to its specific overexpression and aberrant glycosylation in many types of cancers. For the past 30 years, MUC1 has remained a possible diagnostic marker and therapeutic target. Despite initiation of numerous clinical trials, a comprehensively effective therapy with clinical benefit is yet to be achieved. However, the interest in MUC1 as a therapeutic target remains unaltered. For all translational studies, it is important to incorporate updated relevant research findings into therapeutic strategies. In this review we present an overview of the antibodies targeting MUC1 in GI cancers, their potential role in immunotherapy (i.e., antibody-drug and radioimmunoconjugates, CAR-T cells), and other novel therapeutic strategies. We also present our perspectives on how the mechanisms of action of different anti-MUC1 antibodies can target specific hallmarks of cancer and therefore be utilized as a combination therapy for better clinical outcomes.In this study, we investigate the phytochemical profile, anticancer, and antioxidant activities of Teucrium polium methanolic extract using both in vitro and in silico approaches. The results showed the identification of 29 phytochemical compounds belonging to 13 classes of compounds and 20 tripeptides using High Resolution-Liquid Chromatography Mass Spectrometry (HR-LCMS). 13R-hydroxy-9E,11Z octadecadienoic acid, dihydrosamidin, valtratum, and cepharantine were the main compounds identified. The tested extract showed promising antioxidant activities (ABTS-IC50 = 0.042 mg/mL; 1,1-diphenyl-2-picrylhydrazyl (DPPH)-IC50 = 0.087 mg/mL, β-carotene-IC50 = 0.101 mg/mL and FRAP-IC50 = 0.292 mg/mL). Using both malignant Walker 256/B and MatLyLu cell lines, T. polium methanolic extract showed a dose/time-dependent antitumor activity. The molecular docking approach revealed that most of the identified molecules were specifically binding with human peroxiredoxin 5, human androgen, and human progesterone receptors with high binding affinity scores. The obtained results confirmed that T. polium is a rich source of bioactive molecules with antioxidant and antitumor potential.The objectives of the present study are to analyze the different training patterns of the amateur runners, according to their gender, and to find out a correlation between the training pattern and the motivation. The sample was composed of 457 amateur runners. For the collection of data, a two-part questionnaire was used. The first part consisted of questions about sporting and healthy patterns and the second part consisted of the Perception of Success Questionnaire (POSQ), adapted to Spanish. The obtained results indicated that their motives for starting to practice running and to continue their involvement are health and fun. The training pattern is as follows they practise one to three days per week, running from three to five hours overall plus additional stretching and high intensity training. They participated in less than one running event per month. Most of them did not belong to an athletic club, did not have a coach, were not federated and have more than four years' experience of running. What concerns the gender differences, the men trained more than the women, and they did it with relatives and friends; women preferred to do it with friends or by themselves with the assistance of a coach. NBQX mw Age and running hours per week were the best variables to predict the task goal orientation, especially for men. For women, training hours per week predicted the goal orientation but to the ego. This finding could be especially helpful for coaches. A high number of training hours for men was linked with a task goal orientation, and on the other hand, for women it meant an ego goal orientation. The consequences of their behaviours were likely to be markedly different.Internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3) is the most common mutation in patients with acute myeloid leukemia (AML). FLT3-ITD+ induces constitutive activation of FLT3, causing an abnormally rapid proliferation of cancer cells. In this study, we identified novel FLT3 inhibitors and investigated 5-(4-fluorophenyl)-N-phenyloxazol-2-amine (compound 7; 7c) as candidates for the treatment of AML. The results showed that 7c inhibited the activities of FLT3 and mutated FLT3 in a cell-free kinase assay and Molm-13 and MV4-11 cells, as well as the proliferation of FLT3-ITD+ AML cells, increasing apoptosis. The anti-leukemic activity of 7c was confirmed by in vivo tumor growth inhibition in MV4-11 xenograft mice. Besides, 7c suppressed the expression of DNA damage repair genes. Combination treatment with 7c and olaparib (a poly (ADP-ribose) polymerase [PARP] inhibitor) synergistically inhibited cell proliferation in Molm-13 and MV4-11 cells. Our findings demonstrated that 7c is a therapeutic candidate targeting FLT3 for AML treatment and suggested that combination treatment with 7c and a PARP inhibitor may be an effective therapy regimen for FLT3-mutated AML.Ginkgolide C (GGC) derived from Ginkgo biloba, has been reported to exhibit various biological functions. However, the anti-neoplastic effect of GGC and its mechanisms in liver cancer have not been studied previously. Hepatocyte growth factor (HGF)/c-mesenchymal-epithelial transition receptor (c-Met) pathway can regulate tumor growth and metastasis in hepatocellular carcinoma (HCC) cells. This study aimed to evaluate the anti-neoplastic effect of GGC against HCC cells and we observed that GGC inhibited HGF-induced c-Met and c-Met downstream oncogenic pathways, such as PI3K/Akt/mTOR and MEK/ERK. In addition, GGC also suppressed the proliferation of expression of diverse tumorigenic proteins (Bcl-2, Bcl-xL, Survivin, IAP-1, IAP-2, Cyclin D1, and COX-2) and induced apoptosis. Interestingly, the silencing of c-Met by small interfering RNA (siRNA) mitigated c-Met expression and enhanced GGC-induced apoptosis. Moreover, it was noted that GGC also significantly reduced the invasion and migration of HCC cells. Overall, the data clearly demonstrate that GGC exerts its anti-neoplastic activity through modulating c-Met phosphorylation and may be used as an effective therapy against HCC.
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