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... The progression of chronic kidney disease (CKD) increases the risks of cardiovascular morbidity and end-stage kidney disease. Indoxyl sulfate (IS), which is derived from dietary l-tryptophan by the action of bacterial l-tryptophan indole-lyase (TIL) in the gut, serves as a uremic toxin that exacerbates CKD-related kidney disorder. A mouse model previously showed that inhibition of TIL by 2-aza-l-t ...
... 2-Arachidonoylglycerol (2-AG) is the most potent and abundant endocannabinoid that acts as a full agonist at the cannabinoid 1 (CB1) and 2 (CB2) receptors. It serves as a substrate for several serine hydrolases, including monoacylglycerol lipase (MGL), α/β hydrolase domain 6 (ABHD6) and fatty acid amide hydrolase (FAAH). However, 2-AG's rapid conversion to 1-AG (the S stereoisomer) and 3-AG (the R ...
... Obesity and associated complications are becoming a pandemic. Inhibiting fatty acid synthesis and elongation is an important intervention for the treatment of obesity. Despite intensive investigations, many potential therapeutic targets have yet to be discovered. In this study, decreased expression of Hacd2 (a newly found enzyme in fatty acid elongation) was found in HFD induced mice and loss of H ...
... Adipose-derived stem cells (ADSCs), due to their regenerative ability, have beneficial effects on bone and cartilage defects. In addition, spheroid formation of ADSCs obtained using three-dimensional (3D) culture accelerates the regenerative ability of ADSCs. The study investigated the regenerative effect of 3D-cultured small size ADSC spheroids without a scaffold in rats with defects in the criti ...
... Plants have evolved immune systems to fight against pathogens. However, it is still largely unknown how the plant immunity is finely regulated. Here we identified a BTB/POZ domain-containing protein, namely NbBTB, which is predicted to be a member of the ubiquitin E3 ligase complex. The NbBTB expression is downregulated upon the oomycete pathogen Phytophthora parasitica infection. Overexpression o ...
... Engineered natural killer (NK) cell-based therapies have been potentially broadly applicable and exhibited promising results in clinical trials, particularly in the fight against cancers. NK cell immunotherapy however always remains variable. One major obstacle is the inhibitory pathway including PD1/PDL1, providing tumor cells an escape mechanism from immunosurveillance. In this regard, we ration ...
humans; insects; protein synthesis; research; toxicity; viruses
Abstract:
... BacMam system utilizes baculovirus to deliver exogenous genes into mammalian cells and is extensively used for recombinant production of eukaryotic proteins. Here, we described the development of a BacMam vector (pBMCL1), which allows convenient tracing of virus production, provides higher infection efficiency towards mammalian cells, minimizes unwanted transcription of toxic genes in insect cells ...
... Asparagine-linked glycosylation (ALG, N-glycosylation) is one of the most prevalent protein modifications in eukaryotes and regulates protein folding, trafficking and function. Recently, we reported that the mutation of N154Q significantly led to the ER retention of brassinosteroids insensitive 1 (BRI1), the receptor of brassinosteroids (BRs). However, the mechanism of how the N154 site affects BR ...
adults; amino acids; atrophy; cerebellum; cytotoxicity; gain-of-function mutation; gait; gene expression; genes; genetically modified organisms; heterozygosity; histology; ion channels; research
Abstract:
... Specific amino acid substitutions in degenerin mechano-gated channels (DEGs) of C. elegans convert these channels into constitutively active mutants that induce the degeneration of neurons where DEGs are expressed. Acid-sensing ion channel-2a (ASIC2a), a proton-gated cation channel predominantly expressed in central neurons, is a mammalian ortholog of DEGs, and it can remain unclosed to be cytotox ...
... Hemophilia A is a bleeding disorder caused by quantitative or qualitative deficiencies in coagulation factor VIII (FVIII). Low FVIII expression due to its unstable mRNA and binding with immunoglobulin-binding protein (BiP) compromises gene therapy endeavors in hemophilia A. Site-directed mutagenesis have demonstrated an improvement in the expression of FVIII proteins. In this study, a targeted poi ...
DNA; DNA libraries; Severe acute respiratory syndrome coronavirus 2; antibodies; dissociation; glycoproteins; guanine; oligonucleotides; research; systematic evolution of ligands by exponential enrichment; uracil
Abstract:
... Simple, highly sensitive detection technologies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial for the effective implementation of public health policies. We used the systematic evolution of ligands by exponential enrichment with a modified DNA library, including a base-appended base (uracil with a guanine base at its fifth position), to create an aptamer with a high ...
... As the most known therapeutic component of bear bile acids, ursodeoxycholic acid (UDCA) is an FDA-approved drug for the treatment of primary biliary cirrhosis (PBC), the dissolution of cholesterol gallstones. UDCA produces many beneficial effects on metabolism and immune responses via its interaction with the membrane G protein-coupled bile acid receptor (GPBAR); however, how UDCA interacts with G ...
appetite; body weight changes; energy intake; mice; nicotine; oxygen consumption; peptides; research; weight gain
Abstract:
... Smoking cessation increases body weight. The underlying mechanisms, however, have not been fully understood. We here report an establishment of a mouse model that exhibits an augmented body weight gain after nicotine withdrawal. High fat diet-fed mice were infused with nicotine for two weeks, and then with vehicle for another two weeks using osmotic minipumps. Body weight increased immediately aft ...
... At present, the primary culture method of microglia is complicated, and the culture of spinal cord microglia is rare, so we will explore to establish a new and efficient primary culture method of microglia in rats with spinal cord injury (SCI). The SCI model of SD rats was established by modified A11en′s method, and the model of SCI was performed on 1 d, 3 d, 7 d and 14 d respectively. Then the in ...
... MYB genes regulate several different aspects of metabolism and development. However, few studies have reported the involvement of MYBs-CesAs network in the regulation of maize kernel development. In this study, yeast one-hybrid (Y1H) assays and dual-luciferase reporter assays showed that ZmMYB109 activated the expression of ZmCesA5 by directly binding to its promoter. Real-time quantitative PCR (R ...
... The CMP-sialic acid synthetase (CSS) activates free sialic acid (Sia) to CMP-Sia using CTP, and is prerequisite for the sialylation of cell surface glycoconjugates. The vertebrate CSS consists of two domains, a catalytic N-domain and a non-catalytic C-domain. Although the C-domain is not required for the CSS enzyme to synthesize CMP-Sia, its involvement in the catalytic activity remains unknown. F ...
... Pyruvate dehydrogenase kinase 1 (PDK1) is a Ser/Thr kinase that inactivates mitochondrial pyruvate dehydrogenase (PDH), leading to switch of glucose metabolism from mitochondrial oxidation to aerobic glycolysis. We previously reported that PDK1 inhibition is a potent therapeutic strategy in multiple myeloma (MM). However, availability of PDK1 inhibitors, which are effective at low concentrations, ...
... Over 800 known carotenoids are synthesized from phytoene or 4,4′-diapophytoene (dehydrosqualene) characterized by three conjugated double bonds. In this paper, we report that carotenoid desaturase CrtN from Staphylococcus aureus and Methylomonas can accept oxidosqualene, which is the precursor for plant- or animal-type triterpenoids, yielding the yellow carotenoid pigments with 8, 9, or 10 conjuga ...
active sites; fluorescence; guanylate cyclase; humans; hydrogen; metalloproteins; mutagenesis; mutants; research
Abstract:
... Human soluble guanylate cyclase (sGC) is a heme-containing metalloprotein in NO-sGC-cGMP signaling. In this work, fluorescent proteins were employed to study the NO-induced sGC molecular mechanism via mutagenesis at the catalytic domain. The conformational change of sGC by mutant α₁C595 was investigated in living cells through fluorescence lifetime imaging microscopy (FLIM). The results indicated ...
... Hydroxyacyl-CoA dehydrogenase (HADH) catalyzes the third reaction of mitochondrial β-oxidation cascade, while the regulation of its expression and function remains to be elucidated. Using the quantitative translation initiation sequencing (QTI-seq), we have identified that murine Hadh mRNA has two alternative translation start codons. We demonstrated that translation from upstream start codon enco ...