Background: The rst case of a corona virus 2019 (COVID-19) infection in a Sri Lankan was reported on March 11, 2020. The situation in Sri Lanka changed with the rapid increase of personnel contracting COVID-19 in a Naval base camp that housed more than 4000 people. This provided a unique opportunity to study the effectiveness of hydroxychloroquine (HCQ) for post-exposure prophylaxis (PEP), while taking stringent, non-pharmacologic, public health measures to prevent spread. Our aim is to study the effectiveness and safety of HCQ for PEP among naval personnel with exposure to COVID-19 positive patients. Methods/design: This is a placebo-controlled, randomized, clinical trial carried out in the Naval base camp and quarantine centers of the Sri Lanka Navy, Ministry of Defense, Sri Lanka. Navy personnel who are exposed to a patient with con rmed COVID-19 infection but test negative for the virus on reverse, real-time polymerase chain reaction (rRT-PCR) at recruitment will be randomized, 200 to each arm, to receive HCQ or placebo, and monitored for the development of symptoms or rRT-PCR positivity for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) virus for 14 days. Discussion: This trial will provide high-quality evidence of the effectiveness and safety of HCQ as PEP for COVID-19. The study design is unique due to the circumstances of the outbreak in a con ned area among otherwise healthy adults, at a relatively early stage of its spread.
Matrix metalloproteinase (MMP)-14 is the only membrane-anchored MMP that plays a critical role in tumor metastasis and angiogenesis. However, the mechanisms underlying MMP-14 expression in tumors still remain largely unknown. In this study, MMP-14 immunostaining was identified in 29/42 neuroblastoma tissues, which was correlated with clinicopathologic features and shorter patients' survival. In subtotal 20 neuroblastoma cases, microRNA 9 (miR-9) was downregulated and inversely correlated with MMP-14 expression. Bioinformatics analysis revealed a putative miR-9-binding site in the 3 0 -untranslated region (3 0 -UTR) of MMP-14 mRNA. Overexpression or knockdown of miR-9 responsively altered both the mRNA and protein levels of MMP-14 and its downstream gene, vascular endothelial growth factor, in cultured neuroblastoma cell lines SH-SY5Y and SK-N-SH. In an MMP-14 3 0 -UTR luciferase reporter system, miR-9 downregulated the luciferase activity, and these effects were abolished by a mutation in the putative miR-9-binding site. Overexpression of miR-9 suppressed the invasion, metastasis, and angiogenesis of SH-SY5Y and SK-N-SH cells in vitro and in vivo. In addition, the effects of miR-9 on MMP-14 expression, adhesion, migration, invasion, and angiogenesis were rescued by overexpression of MMP-14 in these cells. Furthermore, anti-miR-9 inhibitor or knockdown of MMP-14 respectively increased or inhibited the migration, invasion, and angiogenesis of neuroblastoma cells. These data indicate that miR-9 suppresses MMP-14 expression via the binding site in the 3 0 -UTR, thus inhibiting the invasion, metastasis, and angiogenesis of neuroblastoma.
The discovery of novel drug candidates with anti-severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) potential is
critical for the control of the global COVID-19 pandemic.
Artemisinin, an old antimalarial drug derived from Chinese
herbs, has saved millions of lives. Artemisinins are a cluster
of artemisinin-related drugs developed for the treatment of
malaria and have been reported to have multiple pharmacological
activities, including anticancer, antiviral, and immune
modulation. Considering the reported broad-spectrum antiviral
potential of artemisinins, researchers are interested in whether
they could be used to combat COVID-19. We systematically
evaluated the anti-SARS-CoV-2 activities of nine
artemisinin-related compounds
in vitro
and
carried out a time-of-drug-addition assay to explore their
antiviral mode of action. Finally, a pharmacokinetic prediction
model was established to predict the therapeutic potential of
selected compounds against COVID-19. Arteannuin B showed the
highest anti-SARS-CoV-2 potential with an EC
50
of
10.28 ± 1.12 μM. Artesunate and dihydroartemisinin
showed similar EC
50
values of 12.98 ± 5.30
μM and 13.31 ± 1.24 μM, respectively, which
could be clinically achieved in plasma after intravenous
administration. Interestingly, although an EC
50
of
23.17 ± 3.22 μM was not prominent among the tested
compounds, lumefantrine showed therapeutic promise due to high
plasma and lung drug concentrations after multiple dosing.
Further mode of action analysis revealed that arteannuin B and
lumefantrine acted at the post-entry step of SARS-CoV-2
infection. This research highlights the anti-SARS-CoV-2
potential of artemisinins and provides leading candidates for
anti-SARS-CoV-2 drug research and development.
LP is a minimally invasive, safe, and effective therapy method for UPJ obstruction in children, with shorter hospital stay and excellent outcomes, and without additional risk of postoperative complications. Because of the publishing bias, a series of RCTs are necessary to explore the efficiencies of LP in the management of UPJ obstruction in children.
Long noncoding RNAs (lncRNAs) are reported to be involved in the pathology of numerous cancers, including neuroblastoma (NB). lncRNA SNHG7 has been recognized as a carcinogen in several cancers, but its role in NB progression remains unknown. Our study revealed that SNHG7 expression was markedly higher in NB tissues than that in nontumor tissues. Besides, upregulated SNHG7 was greatly correlated with poor overall survival of NB patients. Functionally, the loss‐of‐function assays demonstrated that knockdown of SNHG7 inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition in NB cells. Mechanically, the bioinformatics analysis predicted that miR‐653‐5p was the shared partner of SNHG7 and signal transducer and activator of transcription 2 (STAT2). Unsurprisingly, we further confirmed that SNHG7 could interact with miR‐653‐5p and therefore functioned as the ceRNA of STAT2 so as to regulate STAT2 expression in NB cells. Moreover, STAT2 expression was in inverse proportion to miR‐653‐5p level but in positive proportion to SNHG7 level in NB tissues. Importantly, the repressed NB progression induced by silenced SNHG7 was reversed by STAT2 overexpression or miR‐653‐5p inhibitors. Jointly, our findings elucidated SNHG7 facilitated NB progression through the miR‐653‐5p/STAT2 pathway, providing a novel therapeutic target and prognostic biomarker for this disease.
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