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#32770803   2020/08/08 To Up

Hypoxia-induced increase in Sug1 leads to poor post-transplantation survival of allogeneic mesenchymal stem cells.

Allogeneic mesenchymal stem cells (MSCs) from young and healthy donors are immunoprivileged and have the potential to treat numerous degenerative diseases. However, recent reviews of clinical trials report poor long-term survival of transplanted cells in the recipient that turned down the enthusiasm regarding MSC therapies. Increasing evidence now confirm that though initially immunoprivileged, MSCs eventually become immunogenic after transplantation in the ischemic or hypoxic environment of diseased tissues and are rejected by the host immune system. We performed in vitro (in rat and human cells) and in vivo (in a rat model) investigations to understand the mechanisms of the immune switch in the phenotype of MSCs. The immunoprivilege of MSCs is preserved by the absence of cell surface immune antigen, major histocompatibility complex II (MHC-II) molecule. We found that the ATPase subunit of 19S proteasome "Sug1" regulates MHC-II biosynthesis in MSCs. Exposure to hypoxia upregulates Sug1 in MSCs and its binding to class II transactivator (CIITA), a coactivator of MHC-II transcription. Sug1 binding to CIITA in hypoxic MSCs promotes the acetylation and K63 ubiquitination of CIITA leading to its activation and translocation to the nucleus, and ultimately MHC-II upregulation. In both rat and human MSCs, knocking down Sug1 inactivated MHC-II and preserved immunoprivilege even following hypoxia. In a rat model of myocardial infarction, transplantation of Sug1-knockdown MSCs in ischemic heart preserved immunoprivilege and improved the survival of transplanted cells. Therefore, the current study provides novel mechanisms of post-transplantation loss of immunoprivilege of MSCs. This study may help in facilitating better planning for future clinical trials.
Ejlal Abu-El-Rub, Niketa Sareen, Glen Lester Sequiera, Hania I Ammar, Weiang Yan, Asmaa M ShamsEldeen, Ilan Rubinchik, Meenal Moudgil, Heba S Shokry, Laila A Rashed, Sanjiv Dhingra

1473 related Products with: Hypoxia-induced increase in Sug1 leads to poor post-transplantation survival of allogeneic mesenchymal stem cells.

1 mg96 tests10 ug96 assays5 x 10A5 cells/vial1 mg1.00 flask1x10e7 cells1050 ul

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#32770789   2020/08/08 To Up

Disulfide-linked allosteric modulators for multi-cycle kinetic control of DNA-based nanodevices.

Nature employs sulfur switches, i.e. redox-active disulfides, to kinetically control biological pathways in a highly efficient and reversible way. Inspired by this mechanism we describe here a DNA-based synthetic nanodevice that acts as a sulfur switch and can be temporally controlled though redox regulation. To do this we rationally designed disulfide DNA strands (modulators) that hybridize to a ligand-binding DNA nanodevice and act as redox-active allosteric regulators inducing the nanodevice to release or load its ligand. Upon reduction, the allosteric modulator spontaneously de-hybridizes from the nanodevice and, as a result, its effect is transient. The system is reversible and has an unprecedented high tolerance to waste products and displays transient behavior for over 40 cycles without significant loss of efficiency. Kinetic control of DNA-based ligand-binding nanodevices through purely chemical reactions paves the way for temporal regulation of more complex chemical pathways.
Erica Del Grosso, Irene Ponzo, Giulio Ragazzon, Leonard J Prins, Francesco Ricci

1747 related Products with: Disulfide-linked allosteric modulators for multi-cycle kinetic control of DNA-based nanodevices.

2 Pieces/BoxTwo 96-Well Microplate Ki 5 G100 μg100ug Lyophilized1

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#32770768   2020/08/08 To Up

The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate.

Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has given rise to emerging respiratory infections with a pandemical diffusion. The vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels in various clinical conditions. The main goal of this study was to evaluate if there is any association between the DBP gene polymorphism at rs7041 and rs4588 loci and the prevalence of COVID-19 and its mortality rates caused among populations of ten countries including Turkey. Positive significant correlations were found between the prevalence (per million) and mortality rates (per million), and GT genotype (p < 0.05) while there was a negative significant correlation between prevalence (per million) and mortality rates (per million), and TT genotype at rs7041 locus among all populations (p < 0.05). However, no significant correlation was found at rs4588 locus. GT genotype was found to confer this susceptibility to the populations of Germany, Mexico, Italy, Czech and Turkey. The variations in the prevalence of COVID-19 and its mortality rates among countries may be explained by Vitamin D metabolism differed by the DBP polymorphisms of rs7041 and rs4588. This article is protected by copyright. All rights reserved.
Lutfiye Karcioglu Batur, Nezih Hekim

1452 related Products with: The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate.

96 tests1 100 UG96 tests

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#32770745   2020/08/08 To Up

Ion Homeostasis for Salinity Tolerance in Plants: A Molecular Approach.

Soil salinity is one of the major environmental stresses faced by the plants. Sodium chloride is the most important salt responsible for inducing salt stress by disrupting the osmotic potential. Due to various innate mechanisms, plants adapt to the sodic niche around them. Genes and transcription factors regulating ion transport and exclusion like Salt Overly Sensitive (SOS), Na /H Exchangers (NHXs), High Sodium Affinity Transporter (HKT) and Plasma membrane protein (PMP) are activated during salinity stress and help in alleviating cells of ion toxicity. For salt tolerance in plants signal transduction and gene expression is regulated via transcription factors such as NAM (no apical meristem), ATAF (Arabidopsis transcription activation factor), CUC (cup-shaped cotyledon), Apetala 2/Ethylene Responsive Factor (AP2/ERF), W-box binding factor (WRKY) and Basic Leucine Zipper Domain (bZIP).Crosstalk between all these transcription factors and genes aid in developing the tolerance mechanisms adopted by plants against salt stress. These genes and transcription factors regulate the movement of ions out of the cells by opening various membrane ion channels. Mutants or knockouts of all these genes are known to be less salt-tolerant compared to wild types. Using novel molecular techniques like analysis of genome, transcriptome, ionome and metabolome of a plant, can help in expanding the understanding of salt tolerance mechanism in plants. In this review, we discuss the genes responsible for imparting salt tolerance under salinity stress through transport dynamics of ion balance and need to integrate high-throughput molecular biology techniques to delineate the issue. This article is protected by copyright. All rights reserved.
Insha Amin, Saiema Rasool, Mudasir A Mir, Wasia Wani, Khalid Z Masoodi, Parvaiz Ahmad

1964 related Products with: Ion Homeostasis for Salinity Tolerance in Plants: A Molecular Approach.

20 ug100ug Lyophilized100 μg100ug100 μg100ug

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#32770723   2020/08/08 To Up

Structure-based design of peptides that trigger Streptococcus pneumoniae cell death.

Toxin-antitoxin (TA) systems regulate key cellular functions in bacteria. Here, we report a unique structure of the Streptococcus pneumoniae HigBA system and a novel antimicrobial agent that activates HigB toxin, which results in mRNA degradation as an antibacterial strategy. In this study, protein structure-based peptides were designed and successfully penetrated the S. pneumoniae cell membrane and exerted bactericidal activity. This result represents the time during which inhibitors triggered S. pneumoniae cell death via the TA system. This discovery is a remarkable milestone in the treatment of antibiotic-resistant S. pneumoniae, and the mechanism of bactericidal activity is completely different from those of current antibiotics. Furthermore, we found that the HigBA complex shows a crossed-scissor interface with two intermolecular β-sheets at both the N- and C-termini of the HigA antitoxin. Our biochemical and structural studies provided valuable information regarding the transcriptional regulation mechanisms associated with the structural variability of HigAs. Our in vivo study also revealed the potential catalytic residues of HigB and their functional relationships. An inhibition study with peptides additionally proved that peptide binding may allosterically inhibit HigB activity. Overall, our results provide insights into the molecular basis of HigBA TA systems in S. pneumoniae, which can be applied for the development of new antibacterial strategies.
Sung-Min Kang, Chenglong Jin, Do-Hee Kim, Sung Jean Park, Sang-Woo Han, Bong-Jin Lee

2372 related Products with: Structure-based design of peptides that trigger Streptococcus pneumoniae cell death.

Two 96-Well Microplate Ki100ug LyophilizedOne 96-Well Microplate Ki100ug LyophilizedOne 96-Well Microplate Ki100ug LyophilizedOne 96-Well Microplate Ki100ug LyophilizedTwo 96-Well Microplate Ki100ug Lyophilized100.00 ug

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#32770587   2020/08/07 To Up

Nucleation of Tiny Silver Nanoparticles Using a Tetrafacial Organic Molecular Barrel for Potential Use in Visible Light Triggered Photocatalysis.

Coordination-driven self-assembly of discrete molecular architectures of diverse shapes and sizes is well studied in last three decades. Use of dynamic imine bond for designing analogous metal-free architectures is a growing challenge in recent time. This article reports an organic molecular barrel (OB4R) as a potential template for nucleation and stabilization of very tiny (< 1.5 nm) Ag nanoparticles (AgNPs). Imine bond condensation of a rigid tetra-aldehyde with a flexible diamine followed by imine-bond reduction yielded the discrete tetragonal organic barrel (OB4R). Presence of molecular pocket ornamented with eight diamine moieties is potential for encapsulation of silver(I). The organic barrel was finally used as a molecular vessel for the controlled nucleation of AgNPs with fine size tuning via binding of Ag(I) ions in the confined space of barrel followed by reduction. Transmission electron microscopic (TEM) analysis of the Ag(0)@OB4R composite revealed that the mean particle size is 1.44±0.16 nm. The composite material has ~52 wt% silver loading. The barrel supported ultrafine AgNPs [Ag(0)@OB4R] are found to be efficient photocatalyst for facile Ullmann-type aryl-amination coupling of haloarenes at ambient temperature without using any additives. The catalyst was stable for several cycles of reuse without any agglomeration. The new composite Ag(0)@OB4R represents the first example of discrete organic-barrel supported AgNPs employed as photocatalyst in Ullmann-type coupling reaction at room temperature.
Partha Sarathi Mukherjee, Bijnaneswar Mondal, Pallab Bhandari

1236 related Products with: Nucleation of Tiny Silver Nanoparticles Using a Tetrafacial Organic Molecular Barrel for Potential Use in Visible Light Triggered Photocatalysis.

5 mg1 mg20 ug100 μg100 μg1 Set

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#32770567   2020/08/07 To Up

Epigallocatechin gallate and theaflavin gallate interaction in SARS-CoV-2 spike-protein central channel with reference to the hydroxychloroquine interaction: Bioinformatics and molecular docking study.

SARS-CoV-2 or COVID-19 pandemic global outbreak created the most unstable situation of human health-economy. In the past two decades different parts of the word experienced smaller or bigger outbreak related to human coronaviruses. The spike glycoproteins of the COVID-19 (similar to SARS-CoV) attach to the angiotensin-converting enzyme (ACE2) and transit over a stabilized open state for the viral internalization to the host cells and propagate with great efficacy. Higher rate of mutability makes this virus unpredictable/less sensitive to the protein/nucleic acid based drugs. In this emergent situation, drug-induced destabilization of spike binding to RBD could be a good strategy. In the current study we demonstrated by bioinformatics (CASTp: computed atlas of surface topography of protein, PyMol: molecular visualization) and molecular docking (PatchDock and Autodock) experiments that tea flavonoids catechin products mainly epigallocatechin gallate or other like theaflavin gallate demonstrated higher atomic contact energy (ACE) value, binding energy, Ki value, ligand efficiency, surface area and more amino acid interactions than hydroxychloroquine (HCQ) during binding in the central channel of the spike protein. Moreover, out of three distinct binding sites (I, II and III) of spike core when HCQ binds only with site III (farthest from the nCoV-RBD of ACE2 contact), epigallocatechin gallate and theaflavin gallate bind all three sites. As sites I and II are in closer contact with open state location and viral-host contact area, these drugs might have significant effects. Taking into account the toxicity/side effects by chloroquine/HCQ, present drugs may be important. Our laboratory is working on tea flavonoids and other phytochemicals in the protection from toxicity, DNA/mitochondrial damage, inflammation and so on. The present data might be helpful for further analysis of flavonoids in this emergent pandemic situation.
Smarajit Maiti, Amrita Banerjee

2983 related Products with: Epigallocatechin gallate and theaflavin gallate interaction in SARS-CoV-2 spike-protein central channel with reference to the hydroxychloroquine interaction: Bioinformatics and molecular docking study.

1 Set1 Set1 Set1 Set1 Set1 Set1 Set1 Set1 Set1 Set1 Set1 Set

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