7,993 results match your criteria: "Institute Of Chemical Biology[Affiliation]"

The design of controllable and precise RNA-targeted CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) systems is an important problem of modern molecular biology and genetic technology. Herein, we have designed a series of photocleavable guide CRISPR RNAs (crRNA) and their 2'-modified (2'-fluoro and locked nucleic acid) analogs containing one or two 1-(2-nitrophenyl)-1,2-ethanediol photolabile linkers (PL). We have demonstrated that these crRNAs can be destroyed by relatively mild UVA irradiation with the rate constants 0.

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Apurinic/apyrimidinic endonuclease 1 (APE1) is responsible for the hydrolysis of the phosphodiester bond on the 5' side of an apurinic/apyrimidinic site during base excision repair. Moreover, in DNA, this enzyme can recognize nucleotides containing such damaged bases as 5,6-dihydro-2'-deoxyuridine (DHU), 2'-deoxyuridine (dU), alpha-2'-deoxyadenosine (αA), and 1,6-ethenoadenosine (εA). Previously, by pulsed electron-electron double resonance spectroscopy and pre-steady-state kinetic analysis, we have revealed multistep DNA rearrangements during the formation of the catalytic complex.

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R-loops can act as replication fork barriers, creating transcription-replication collisions and inducing replication stress by arresting DNA synthesis, thereby possibly causing aberrant processing and the formation of DNA strand breaks. RNase H1 (RH1) is one of the enzymes that participates in R-loop degradation by cleaving the RNA strand within a hybrid RNA-DNA duplex. In this study, the kinetic features of the interaction of RH1 from with R-loops of various structures were investigated.

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Chronic immunoinflammatory rheumatic diseases, such as axial spondyloarthritis (AxSpA), are accompanied by a dysregulation of bone remodeling. Among potential biomarkers of bone metabolism, the Wnt pathway antagonist, Dickkopf-1 (DKK-1), is of particular interest because of its potential to reflect a shift towards joint ossification or osteoporosis, but its diagnostic value needs validation. There is still a lack of stable and efficient methods of measuring serum DKK-1 levels suitable for longitude studies.

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The mechanism of transcription proceeds through the formation of R-loop structures containing a DNA-RNA heteroduplex and a single-stranded DNA segment that should be placed inside the elongation complex; therefore, these nucleic acid segments are limited in length. The attachment of each nucleotide to the 3' end of an RNA strand requires a repeating cycle of incoming nucleoside triphosphate binding, catalysis, and enzyme translocation. Within these steps of transcription elongation, RNA polymerase sequentially goes through several states and is post-translocated, catalytic, and pre-translocated.

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Respiratory infections caused by RNA viruses are a major contributor to respiratory disease due to their ability to cause annual epidemics with profound public health implications. Influenza A virus (IAV) infection can affect a variety of host signaling pathways that initiate tissue regeneration with hyperplastic and/or dysplastic changes in the lungs. Although these changes are involved in lung recovery after IAV infection, in some cases, they can lead to serious respiratory failure.

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Artificial lipids have become increasingly important in generating novel nanoenzymes and nanoparticles. Imidazole has been well established as a versatile catalyst in synthetic chemistry and through its related amino acid histidine in enzymes. By exploiting the transphosphatidylation reaction of phospholipase D, the choline headgroup of phosphatidyl choline was exchanged for the imidazole moiety containing histidinol.

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/: Neutrophils have recently gained significant attention due to their heterogeneity in tumor settings. The gene expression profiles of neutrophils from different tumor types are of great interest. Murine splenic neutrophils reflect the immune status of the organism and could be a source of tumor-associated neutrophils in tumor-bearing mice.

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Article Synopsis
  • Lung cancer is a major global health issue, with challenges in early detection and relapse identification; blood-based liquid biopsies show potential in non-invasive monitoring.
  • Researchers used a comprehensive approach combining various datasets to identify candidate biomarkers in non-small cell lung cancer (NSCLC), connecting them to specific molecular pathways.
  • Results indicated that certain metabolites and RNA expressions in plasma EVs correlate with disease progression and overall survival in NSCLC patients, highlighting their potential as prognostic biomarkers.
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Corrigendum to "Drug discovery targeting Na1.8: Structural insights and therapeutic potential" [Curr Opin Chem Biol 83 (2024) 102538].

Curr Opin Chem Biol

November 2024

Beijing Frontier Research Center for Biological Structures, State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; Institute of Bio-Architecture and Bio-Interactions (IBABI), Shenzhen Medical Academy of Research and Translation (SMART), Guangming District, Shenzhen 518107, Guangdong Province, China; Institute of Chemical Biology, Shenzhen Bay Laboratory, Guangming District, Shenzhen 518132, Guangdong Province, China. Electronic address:

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Alzheimer's Disease (AD) is an incurable and debilitating progressive, neurodegenerative disorder which is the leading cause of dementia worldwide. Neuropathologically, AD is characterized by the accumulation of Aβ amyloid plaques in the microenvironment of brain cells and neurovascular walls, chronic neuroinflammation, resulting in neuronal and synaptic loss, myelin and axonal failure, as well as significant reduction in adult hippocampal neurogenesis. The hippocampal formation is particularly vulnerable to this degenerative process, due to early dysfunction of the cholinergic circuit.

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Cholesterol-driven modulation of membrane-membrane interactions by an antimicrobial peptide, NK-2, in phospholipid vesicles.

Biochem Biophys Res Commun

December 2024

Soft Matter and Biophysics Laboratory, Department of Physics, Jadavpur University, 188, Raja S. C. Mullick Road, Kolkata, 700032, India. Electronic address:

Antimicrobial peptides (AMPs) are essential components of the innate immune system, demonstrating their antimicrobial effects primarily through the creation of transmembrane pores that result in membrane disruption. Cholesterol within the membrane can significantly affect the interaction between AMPs and the membrane, as it is known to alter both the permeability and elastic properties of the membrane. In this study, we have investigated the influence of cholesterol on the interaction of the AMP, NK-2 with phospholipid vesicles.

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A TEMPO-N charge-transfer complex enables the electrochemical C-H azidation of various N-heterocycles. The TEMPO ion, generated from TEMPO, assists in producing N by forming a TEMPO-N complex with N . The formation of this complex is supported by UV-vis absorption spectra, cyclic voltammetry studies, and ESI-HRMS studies.

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Molecular Design of Phthalocyanine-Based Drug Coassembly with Tailored Function.

J Am Chem Soc

December 2024

State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.

Coassemblies with tailored functions, such as drug loading, tissue targeting and releasing, therapeutic and/or imaging purposes, and so on, have been widely studied and applied in biomedicine. design of these coassemblies hinges on an integrated approach involving synergy between various design strategies, ranging from structure screening of combinations of "phthalocyanine-chemotherapeutic drug" molecules for molecular scaffolds, exploration of related fabrication principles to verification of intended activity of specific designs. Here, we propose an integrated approach combining computation and experiments to design from scratch coassembled nanoparticles.

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The cannabinoid CB receptor positive allosteric modulator EC21a exhibits complicated pharmacology .

J Recept Signal Transduct Res

August 2024

Department of Pharmacology and Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, USA.

Schizophrenia is a complex disease involving the dysregulation of numerous brain circuits and patients exhibit positive symptoms (hallucinations, delusions), negative symptoms (anhedonia), and cognitive impairments. We have shown that the antipsychotic efficacy of positive allosteric modulators (PAMs) of both the M muscarinic receptor and metabotropic glutamate receptor 1 (mGlu) involve the retrograde activation of the presynaptic cannabinoid type-2 (CB) receptor, indicating that CB activation or potentiation could result in a novel therapeutic strategy for schizophrenia. We used two complementary assays, receptor-mediated phosphoinositide hydrolysis and GIRK channel activation, to characterize a CB PAM scaffold, represented by the compound EC21a, to explore its potential as a starting point to optimize therapeutics for schizophrenia.

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Article Synopsis
  • * The process begins with engineering a biosynthetic pathway to produce drimenol, followed by the use of an engineered enzyme for a specific hydroxylation reaction.
  • * Finally, a nickel-catalyzed reductive coupling technique is employed to synthesize various drimane meroterpenoids in a streamlined and enantiospecific way, which could lead to further optimization of their biological activities.
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Discovery of gallic acid-based mitochondriotropic antioxidant attenuates LPS-induced neuroinflammation.

Free Radic Biol Med

January 2025

Department of Bioscience and Bioengineering, Indian Institute of Technology, Jodhpur, NH 62, Surpura Bypass Road, Karwar, Rajasthan, 342037, India; Smart Healthcare, Interdisciplinary Research Platform, Indian Institute of Technology Jodhpur, Karwar, Rajasthan, 342037, India; Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Raja S. C. Mullick Road, Jadavpur, Kolkata, 700 032, West Bengal, India. Electronic address:

Mitochondria are complex organelle that plays a pivotal role in energy metabolism, regulation of stress responses, and also serve as a major hub for biosynthetic processes. In addition to their well-established function in cellular energetics, it also serves as the primary site for the origin of intracellular reactive oxygen species (ROS), which function as signaling molecules and can lead to oxidative stress when generated in excess. Moreover, mitochondrial dysfunction is one of the leading cause of neuroinflammation.

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Noroviruses (family Caliciviridae) are common causes of acute gastroenteritis worldwide. Multiple polymerase/capsid combinations have been identified among members of norovirus genogroup GII, at least 10 of which contain GII.P16 polymerase.

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New phosphate-modified nucleic acid derivatives are of great significance in basic research and biomedical applications. We have recently developed a new class of phosphoramide benzoazole oligonucleotides (PABAOs). In this work, th properties of N-benzoxazole oligodeoxyribonucleotides have been thoroughly examined.

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The recent advancements on membrane protein degraders (MPDs) have broadened the applicability of proteolysis-targeting chimeras (PROTACs) beyond intracellular proteins to include the previously "undruggable" cell-surface targets. However, the potential toxicity of MPDs caused by undesired off-target degradation poses a significant challenge to clinical deployment, mirroring concerns associated with PROTACs. Here, we introduce a conditionally activatable membrane protein degrader (Pro-MPD), which leverages the specificity and high affinity of biparatopic nanobodies combined with a tumor microenvironment-activated cell-penetrating peptide (Pro-CPP) to achieve on-target activated internalization and degradation of PD-L1 within tumor sites.

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Traumatic brain injuries (TBIs) cause multifaceted disruption in the neural network, initiate huge inflammation processes, and form glial scars that result in severe damage to the brain. Thus, the treatment of TBI is a challenging task. To address this challenge, a newer and innovative approach is extremely important to develop a successful therapeutic strategy.

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Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor transcription factor that regulates gene expression programs in response to ligand binding. Endogenous and synthetic ligands, including covalent antagonist inhibitors GW9662 and T0070907, are thought to compete for the orthosteric pocket in the ligand-binding domain (LBD). However, we previously showed that synthetic PPARγ ligands can cooperatively cobind with and reposition a bound endogenous orthosteric ligand to an alternate site, synergistically regulating PPARγ structure and function (Shang et al.

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Biomimetic Targeted Co-Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma.

Adv Sci (Weinh)

January 2025

Department of Musculoskeletal Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

Article Synopsis
  • Chemotherapy's limited success in treating osteosarcoma is linked to its high variability and severe side effects, prompting a genomic analysis that reveals two critical traits: CDK4 amplification and homologous recombination repair deficiency.
  • A novel co-delivery system using metal-organic frameworks (MOFs) is developed to effectively deliver CDK4/6 and PARP inhibitors, improving drug solubility and release control in the tumor environment.
  • This targeted approach not only enhances direct tumor targeting and synergistic drug effects but also boosts immune response, potentially transforming osteosarcoma treatment into a more effective and innovative strategy.
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The Emerging Roles of Multimolecular G-Quadruplexes in Transcriptional Regulation and Chromatin Organization.

Acc Chem Res

December 2024

Imperial College London, Department of Chemistry, Molecular Sciences Research Hub, 82 Wood Lane, London W12 0BZ, U.K.

Article Synopsis
  • G-quadruplexes (G4s) are non-canonical DNA structures that potentially regulate biological processes, particularly transcription, when located at gene promoters.
  • Recent studies reveal that G4s may enhance transcription rather than inhibit it, contradicting the traditional view that they act as blockades to the elongation of RNA polymerase.
  • The research focuses on multimolecular G4s (mG4s), which can facilitate transcription through mechanisms like phase separation and the recruitment of chromatin-remodeling proteins, emphasizing their significant role in gene regulation.
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Mammalian nucleotide excision repair (NER), known for its broad substrate specificity, is responsible for removal of bulky lesions from DNA. Over 30 proteins are involved in NER, which includes two distinct pathways: global genome NER and transcription-coupled repair. The complexity of these processes, the use of extended DNA substrates, and the presence of bulky DNA lesions induced by chemotherapy have driven researchers to seek more effective methods by which to assess NER activity, as well as to develop model DNAs that serve as efficient substrates for studying lesion removal.

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