The prevailing crisis caused by the COVID-19 pandemic demands the development of effective therapeutic agents that can be implemented with minimal to zero adverse effects.
 
  Vitex negundo L. (VNL) is a medicinal plant with reported efficacy against respiratory diseases and some of the COVID-19 symptoms. Funded by the Department of Science and Technology (DOST), the University of the Philippines - Philippine General Hospital (UP-PGH) is currently conducting clinical trials of VNL and other medicinal plants as adjuvant therapeutic agents against mild cases of COVID-19. The basis for the clinical trials is primarily the pharmacological efficacy of the medicinal plants against respiratory disorders and associated COVID-19 symptoms.
 
  This study assessed the in silico potential of VNL components against SARS-CoV-2 main protease (Mpro), an enzyme that plays an important role in COVID-19, the disease caused by the SARS-CoV-2.
 
  Phytochemical mining of VNL components from the literature was conducted. A database cohibitors and a promising adjuvant therapeutic agent against COVID-19 or its symptoms. Furthermore, the study offers a rationale on phytochemical mining from medicinal plants as a means that can be implemented in the early stage of a drug discovery and development program.
 This in silico study identified VNL as a potential single source of a cocktail of SARS-CoV-2 Mpro inhibitors and a promising adjuvant therapeutic agent against COVID-19 or its symptoms. Furthermore, the study offers a rationale on phytochemical mining from medicinal plants as a means that can be implemented in the early stage of a drug discovery and development program.
  The function of MALAT1, a kind of long non-coding RNAs (lncRNA), in HER2-positive breast cancer remains largely unexplored. Therefore, there is a need investigate the effect of MALAT1 on tumor development in HER2-positive breast cancer.
 
  We detected MALAT1 expression in HER2-positive breast cancer cells and tissues and analyzed the effects of MALAT1 on cell proliferation in HER2-positive breast cancer cell lines (BT-474 and SKBR3).
 
  A mouse xenograft model was established for detecting the function of MALAT1 in HER2-positive breast cancer.
 
  As a result, MALAT1 was remarkably up-regulated in HER2-positive breast cancer both in cells and tissues. In addition, the silence of MALAT1 inhibited the proliferation of HER2-positive breast cancer cells both in vitro and in vivo. Furthermore, the knockdown of MALAT1 by shRNA down-regulated DNMT1, DNMT3a, and DNMT3b, while up-regulated BRCA1 and PTEN in HER2-positive breast cancer both in cell lines and mouse xenograft models.
 
  In short, MALAT1 might be a potential biomarker and therapeutic target for HER2-positive breast cancer therapy.
 In short, MALAT1 might be a potential biomarker and therapeutic target for HER2-positive breast cancer therapy.
  Complement component 3 (C3) receptors play an important role as an inflammatory mediator in the innate immune system, although their mechanism was not well studied during constipation.
 
  The aim of this study is to investigate the regulatory role of C3 and its receptors' downstream signaling during constipation.
 
  Alterations in the C3, C3a receptor (C3aR), and C3b receptor (C3bR) expressions, PI3K/AKT pathway, RhoA/MLC pathway, MAP kinase pathway, and inflammatory cytokine expressions were measured in the transverse colon of loperamide (Lop) treated SD rats.
 
  Lop treatment successfully induced constipation phenotypes, including decreased stool parameters and histological structure alterations. The expression levels of C3 were significantly increased, whereas expressions of C3aR and C3bR were observed to decrease during Lop-induced constipation. Moreover, significant upregulation was observed in the phosphorylation levels of PI3K, AKT, and GSK3 in transverse colons of Lop treated SD rats.  https://www.selleckchem.com/products/pf-04620110.html  The expression of RhoA and phosphorylation of MLC were also enhanced in the Lop treated group. Furthermore, a similar pattern was detected in the MAP kinase pathway and inflammatory cytokine expressions. Subsequent to Lop treatment, the phosphorylation of ERK and p38, as well as the mRNA levels of NF-κB, TNF-α, IL-6 and IL-1α were remarkably increased in the transverse colon.
 
  These results indicate that Lop-induced constipation is tightly linked to the downregulation of C3aR and C3bR expressions and upregulation of the C3, C3Rs downstream signaling pathway, including PI3K/AKT, RhoA/MLC, and MAP kinase pathways as well as inflammatory cytokine expressions in the transverse colon of SD rats.</P>.
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  We aim to define parameters affecting the safety and long-term transgene expression of attenuated HSV-1 vectors and optimize the expression cassettes to achieve robust and sustained expression in CNS.
 
  Engineered, attenuated Herpes simplex virus (HSV) vectors are promising vehicles for gene delivery to the peripheral and central nervous systems. The virus latent promoter (LAP) is commonly used to drive exogenous gene expression; however, parameters affecting the safety and long-term transgene expression of attenuated HSV-1 vectors have not been fully understood.
 
  This study aimed to construct attenuated HSV-1 vectors using the CRISPR-Cas9 system and examine the influence of transgene cassette construction and insertion site on transgene expression and vector safety.
 
  In this study, we used a CRISPR-Cas9 system to accurately and efficiently edit attenuated HSV-1 strain 1716, and constructed two series of recombinant virus LMR and LMRx with different sets of gene cassettes insertion in Exon1(LAP2) and 2.0 oter activity during latency. Besides, over-transcription of the downstream part of LAT may induce continuous activation of the attenuated vectors, suggesting an important role of LAT in maintaining viral reactivation potential.
  Scaffold-based gene therapy provides a promising approach for tissue engineering, which is important and popular, that combines medical applications with engineering materials knowledge.
 
  The decellularization techniques were employed to remove the cellular components from porcine elastic cartilages, leaving a native decellularized extracellular matrix(dECM) composition and architecture integrity of largely insoluble collagen, elastin, and tightly bound glycosaminoglycans. For newly designed collagen scaffold samples, elastic cartilages was hydrolyzed by protease with different concentrations. In this way, it could gain state completely and clearly.
 
  An extraction process of supercritical carbon dioxide(ScCO2) was used to remove cellular components from porcine elastic cartilage. The dECM scaffolds with collagen must be characterized by Fourier transform infrared spectroscopy(FTIR), thermo-gravimetric analysis (TGA), and scanning electron microscope(SEM).
 
  The study provided a new treatment combined with supercritical carbon dioxide and alkaline/protease to prepare dECM scaffolds with hole-scaffold microstructures and introduce into a potential application on osteochondral tissue engineering using scaffold-based gene therapy.