A5074639267- HIV/AIDS drug development and treatment
- Epigenetics and DNA Methylation
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Cancer-related gene regulation
- RNA modifications and cancer
- Drug Transport and Resistance Mechanisms
- Hepatitis C virus research
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Analytical Methods in Pharmaceuticals
- Wnt/β-catenin signaling in development and cancer
- Clinical Nutrition and Gastroenterology
- Genomics and Chromatin Dynamics
- Pharmacological Effects and Toxicity Studies
- Hepatitis B Virus Studies
- Enhanced Recovery After Surgery
- Mass Spectrometry Techniques and Applications
- RNA Interference and Gene Delivery
- Poxvirus research and outbreaks
- Extracellular vesicles in disease
- Opioid Use Disorder Treatment
- Bioactive Compounds and Antitumor Agents
- Immune Cell Function and Interaction
- Immune cells in cancer
Gilead Sciences (United States)
2011-2025
Guangdong Academy of Medical Sciences
2021-2025
Army Medical University
2025
Southwest Hospital
2025
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2025
Guangdong Provincial People's Hospital
2021-2025
Southern Medical University
2024-2025
United States Military Academy
2023
Shenzhen Luohu People's Hospital
2020-2022
Shenzhen University
2020-2022
Abstract Liquid–liquid phase‐separated (LLPS) transcriptional factor assemblies at super‐enhancers (SEs) provide a conceptual framework for underlying control in mammal cells. However, the mechanistic understanding of LLPS aberrant transcription driven by dysregulation SEs human malignancies is still elusive. By integrating SE profiling and core regulatory circuitry (CRC) calling algorithm, CRC metastatic chemo‐resistant osteosarcoma delineated. components, HOXB8 FOSL1, produce dense dynamic...
Abstract The adaptation of osteosarcoma cells to therapeutic pressure impedes the efficacy chemotherapy for osteosarcoma. However, characteristics and cellular organization therapy-resistant in tumors remain elusive. Here, we utilized single-cell transcriptomics systematically map cell-type-specific gene expression a chemotherapy-resistant tumor. Our data demonstrated VEGFR2-JMJD3-abundant subsets as quiescent stem-like cells, thereby establishing hierarchy actively cycling progenitor pools...
Pteridinone-based Toll-like receptor 7 (TLR7) agonists were identified as potent and selective alternatives to the previously reported adenine-based agonists, leading discovery of GS-9620. Analogues optimized for immunomodulatory activity selectivity versus other TLRs, based on differential induction key cytokines including interferon α (IFN-α) tumor necrosis factor (TNF-α). In addition, physicochemical properties adjusted achieve desirable in vivo pharmacokinetic pharmacodynamic properties....
Absorption, distribution, metabolism and elimination of doravirine (MK-1439), a novel non-nucleoside reverse transcriptase inhibitor, were investigated. Two clinical trials conducted in healthy subjects: an oral single dose [14 C]doravirine (350 mg, ∼200 µCi) trial (n = 6) intravenous (IV) single-dose (100 µg) 12). In vitro metabolism, protein binding, apparent permeability P-glycoprotein (P-gp) transport studies to complement the trials.Following administration, all administered was...
Abstract Osteosarcoma (OS) is a common type of bone tumor for which there has been limited therapeutic progress over the past three decades. The prevalence transcriptional addiction in cancer cells emphasizes biological significance and clinical relevance super-enhancers. In this study, we found that Max-like protein X (MLX), member Myc-MLX network, driven by Upregulation MLX predicts poor prognosis osteosarcoma. Knockdown impairs growth metastasis osteosarcoma vivo vitro. Transcriptomic...
Ovarian cancer (OC) is the most lethal gynecologic cancer.
Abstract Osteosarcoma is an aggressive malignancy with poor prognosis. Super-enhancers (SE) have been highlighted as critical oncogenic elements required for maintaining the cancer cell characteristics. However, regulatory role of SEs in osteosarcoma properties has not yet elucidated. In current study, we found that cells and clinical specimens shared a significant fraction SEs. Moreover, leukemia-inhibitory factor (LIF) was identified essential under control osteosarcoma-specific SE. The...
The development of new and improved antiretroviral therapies that allow for alternative dosing schedules is needed people living with HIV-1. Islatravir a deoxyadenosine analog in the treatment HIV-1 suppresses replication via multiple mechanisms action, including reverse transcriptase translocation inhibition delayed chain termination. differentiated from other antiretrovirals by its high potency, long t½, broad tissue distribution, favorable drug resistance profile. A comprehensive...
Despite suppressive antiretroviral therapy (ART), HIV-1 persists in latent reservoirs that seed new HIV infections if ART is interrupted, necessitating lifelong for people with HIV. Activation of during could improve recognition and elimination infected cells by the immune system. Protein kinase C (PKC) isozymes increase transcription hence are potential latency reversal agents. However, clinical utility PKCs this application limited due to toxicity, which poorly understood. Our studies...
Abstract Osteosarcoma, the most prevalent malignant bone tumor among adolescents, frequently exhibits limited responsiveness to immunotherapy, a challenge attributed poorly understood underlying mechanisms. Here, we identify enhanced polyamine biosynthesis as key driver of osteosarcoma progression and immunotherapy resistance. We show that cell proliferation growth rely on availability disruption synthesis significantly boosts cytotoxic efficacy TCR-engineered T cells against cells....
E-cadherin, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs) are important molecules involved in tumor metastasis. In this study, we examined the expressions of VEGF, MMP-1, MMP-2, microvessel density (MVD), as well microlymphatic vessel (MLVD) 200 cases gastric cancer tissues, determined relationship between these parameters clinicopathological features patient survival. Protein expressions, MVD, MLVD were detected by immunohistochemistry. The correlation...
H3K27me3 modification inactivates gene transcription by resulting in condensed chromatin. However, the landscape and biological functions of breast cancer remain unclear.Fluorescence enzyme assay was used to analyze cell proliferation. Transwell test ability migration invasion MDA-MB-231 cells with designed treatment. Transfection exogenous plasmid intervene specific expression. Nude mouse tumor xenograft model employed detect effect GSKJ-4 vivo. ChIP-Seq analyzed state around TSS CEMIP....
Abstract Epigenetic dysregulation contributes to bladder cancer tumorigenesis. H3K36me2 demethylase KDM2A functions as an important epigenetic regulator of cell fate in many types tumors. However, its role remains unknown. Here, we revealed a positive correlation between gene copy number gain and upregulation mRNA expression cancer. Moreover, super-enhancer (SE) driving transcription was found high-grade cancer, resulting significantly higher compared that low-grade knockdown (KD) decreased...
Replication-competent human immunodeficiency virus (HIV) persists in infected people despite suppressive combination antiretroviral therapy (cART), and it represents a major obstacle to HIV functional cure or eradication. We have developed model of cART-mediated viral suppression simian (SIV) mac239-infected Indian rhesus macaques evaluated the impact histone deacetylase inhibitor (HDACi) romidepsin (RMD) on viremia vivo. Eight virologically suppressed clinically relevant levels (<30 RNA...
Islatravir (MK-8591) is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment and prevention of HIV-1. The potential islatravir to interact with commonly co-prescribed medications was studied vitro. Elimination expected be balanced between adenosine deaminase–mediated metabolism renal excretion. did not inhibit uridine diphosphate glucuronosyltransferase 1A1 or cytochrome p450 (CYP) enzymes CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, nor it induce 3A4....
Abstract Because no currently available vaccine can prevent HIV infection, pre-exposure prophylaxis (PrEP) with antiretrovirals (ARVs) is an important tool for combating the pandemic 1,2 . Long-acting ARVs promise to build on success of current PrEP strategies, which must be taken daily, by reducing frequency administration 3 GS-CA1 a small-molecule capsid inhibitor picomolar antiviral potency against broad array strains, including variants resistant existing ARVs, and has shown long-acting...
Long-acting antiretroviral agents for preexposure prophylaxis (PrEP) represent a promising new alternative to daily oral regimens HIV prevention. Lenacapavir (LEN) is first-in-class long-acting capsid inhibitor approved the treatment of HIV-1 infection. Here, we assessed efficacy LEN PrEP using single high-dose simian-human immunodeficiency virus (SHIV) rectal challenge macaque model. In vitro, showed potent antiviral activity against SHIV, as it did HIV-1. macaques, subcutaneous...
In this study, induction and inhibition of rhesus monkey CYP3A64 versus human CYP3A4 were characterized in vitro, the corresponding pharmacokinetic consequences evaluated monkeys. hepatocytes, rifampin markedly induced mRNA (EC<sub>50</sub> = 0.5 μM; <i>E</i><sub>max</sub> 6-fold) midazolam (MDZ) 1′-hydroxylase activity 0.2 2-fold). Compound A...