The outbreak of novel coronavirus (COVID-19) infections occurring in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking strategies to repurpose HIV protease inhibitors and nucleotide analogues for COVID-19. The evaluation was made on docking scores calculated by AutoDock Vina and RosettaCommons. Preliminary results suggested that Indinavir and Remdesivir have the best docking scores and the comparison of the docking sites of these two drugs shows a near perfect dock in the overlap region of the protein pocket. However, the active sites inferred from the proteins of SARS coronavirus are not compatible with the docking site of COVID-19, which may give rise to concern in the efficacy of drugs.

Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFb-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/ SMAD2/3 repressor complex in TGFb-mediated lung cancer metastasis. Cancer Res; 74(24); 7333-43. Ó2014 AACR.

Prostate-derived Ets (E-twenty six) factor (PDEF), an epithelium-specific member of the Ets family of transcription factors, has been shown to play a role in suppressing the development of many epithelium-derived cancers such as prostate and breast cancer. It is not clear, however, whether PDEF is involved in the development or progression of bladder cancer. In a comparison between normal urothelium and bladder tumor tissue, we identified significant decreases of PDEF in the tumor tissue. Further, the immunohistochemistry assays indicated a significantly higher immunostaining of PDEF in low-grade bladder tumors. Additionally, the highly differentiated transitional-cell bladder carcinoma RT-4 cells expressed significantly more PDEF levels than the bladder carcinoma HT1376 and the T24 cells. Ectopic overexpression of PDEF attenuated proliferation, invasion, and tumorigenesis of bladder carcinoma cells in vitro and in vivo. PDEF enhanced the expression levels of mammary serine protease inhibitor (MASPIN), N-myc downstream regulated gene 1 (NDRG1), KAI1, and B-cell translocation gene 2 (BTG2). PDEF modulated epithelial-mesenchymal-transition (EMT) by upregulating E-cadherin expression and downregulating the expression of N-cadherin, SNAIL, SLUG, and vimentin, leading to lower migration and invasion abilities of bladder carcinoma cells. Filamentous actin (F-actin) polarization and remodeling were observed in PDEF-knockdown RT-4 cells. Our results suggest that PDEF gene expression is associated with the extent of bladder neoplasia and PDEF modulated the expressions of EMT-related genes. The induction of BTG2, NDRG1, MASPIN, and KAI1 gene expressions by PDEF may explain the inhibitory functions of PDEF on the proliferation, invasion, and tumorigenesis in bladder carcinoma cells.

A series of pyrrole-indolin-2-ones were synthesized, and their inhibition profile for Aurora kinases was studied. The potent compound 33 with phenylsulfonamido at the C-5 position and a carboxyethyl group at the C-3' position selectively inhibited Aurora A over Aurora B with IC50 values of 12 and 156 nM, respectively. Replacement of the carboxyl group with an amino group led to compound 47, which retained the activity for Aurora B and lost activity for Aurora A (IC50=2.19 microM). Computation modeling was used to address the different inhibition profiles of 33 and 47. Compounds 47 and 36 (the ethyl ester analogue of 33) inhibited the proliferation of HCT-116 and HT-29 cells and suppressed levels of the phosphorylated substrates of Aurora A and Aurora B in the Western blots.

Growth differentiation factor-15 (GDF15),Urinary bladder carcinoma is the fourth leading malignancy in American males and the eighth most common cause of malignancy-related death 1 . Approximately 20% to 25% of primary bladder cancers have invaded the muscle layer of the bladder wall by the time they were diagnosed, and thus suggesting a poor prognosis; in addition, seventy percent of papillary and superficial tumors recur within two years of surgical excision 2 . Because the effective strategies for early detection of bladder cancer remain elusive,

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We concluded that the new technique of NRH can reduce postoperative bladder dysfunctions.

Background: The timing of transcranial direct current stimulation (tDCS) with neurorehabilitation interventions may affect its modulatory effects. Motor function has been reported to be modulated by the timing of tDCS; however, whether the timing of tDCS would also affect restoration of daily function and upper extremity motor control with neurorehabilitation in stroke patients remains largely unexplored. Mirror therapy (MT) is a potentially effective neurorehabilitation approach for improving paretic arm function in stroke patients. This study aimed to determine whether the timing of tDCS with MT would influence treatment effects on daily function, motor function and motor control in individuals with chronic stroke. Methods: This study was a double-blinded randomized controlled trial. Twenty-eight individuals with chronic stroke received one of the following three interventions: (1) sequentially combined tDCS with MT (SEQ), (2) concurrently combined tDCS with MT (CON), and (3) sham tDCS with MT (SHAM). Participants received interventions for 90 min/day, 5 days/week for 4 weeks. Daily function was assessed using the Nottingham Extended Activities of Daily Living Scale. Upper extremity motor function was assessed using the Fugl-Meyer Assessment Scale. Upper extremity motor control was evaluated using movement kinematic assessments. Results: There were significant differences in daily function between the three groups. The SEQ group had greater improvement in daily function than the CON and SHAM groups. Kinematic analyses showed that movement time of the paretic hand significantly reduced in the SEQ group after interventions. All three groups had significant improvement in motor function from pre-intervention to post-intervention.