A5033602621- Amino Acid Enzymes and Metabolism
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- interferon and immune responses
- Renal cell carcinoma treatment
- Biochemical Acid Research Studies
- Renal and related cancers
- Cytokine Signaling Pathways and Interactions
- Nanoplatforms for cancer theranostics
- Cancer Genomics and Diagnostics
- Radiopharmaceutical Chemistry and Applications
- Cancer therapeutics and mechanisms
- Sphingolipid Metabolism and Signaling
- Viral Infections and Vectors
- RNA modifications and cancer
- Tryptophan and brain disorders
- X-ray Diffraction in Crystallography
- Immune Response and Inflammation
- Histone Deacetylase Inhibitors Research
- Crystallization and Solubility Studies
- Gut microbiota and health
- Estrogen and related hormone effects
- Glycosylation and Glycoproteins Research
Shanghai Institute of Materia Medica
2015-2024
Chinese Academy of Sciences
2015-2024
University of Chinese Academy of Sciences
2017-2024
Yale University
2016-2023
State Key Laboratory of Drug Research
2023
Central South University
2023
Chinese National Human Genome Center
2012
Shanghai Institute of Hematology
2009-2012
Ruijin Hospital
2009-2012
Shanghai Jiao Tong University
2009
Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet role of microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link neuroinflammation progression. Using mouse models, discovered that, during alteration composition leads to peripheral accumulation phenylalanine isoleucine, which stimulates differentiation proliferation pro-inflammatory T helper 1 (Th1) cells. The...
The critical challenge for cancer vaccine-induced T-cell immunity is the sustained activation of antigen cross-presentation in antigen-presenting cells (APCs) with innate immune stimulation. In this study, it first discovered that clinically used magnetic contrast agents, iron oxide nanoparticles (IONPs), markedly augment type-I interferon (IFN-I) production profile stimulator genes (STING) agonist MSA-2 and achieve a 16-fold dosage-sparing effect human STING haplotype. Acid-ionizable...
• MDD has substantial changes in the structure and function of gut microbiota. exhibited decreased amino acids bile increased lipids blood. The blood immune cell subtypes tend to promote inflammation. could be divided into two subtypes, one is correlated with relapse. We revealed integrative discriminative signatures for distinguishing from HC. Major depressive disorder (MDD) involves systemic peripheral microbiota, but current understanding incomplete. Herein, we conducted a multi-omics...
Significance Parts of clear cell renal carcinomas (ccRCCs) sometimes have histologic features characteristic a sarcoma. So-called sarcomatoid tumors are more aggressive, difficult to treat, and associated with poor prognosis. Their pathogenesis has been uncertain. Through separate exome sequencing carcinomatous components, we show that these components share many somatic mutations, including in genes ccRCC. Sarcomatoid elements had significantly new particularly cancer driver genes, than...
Curcumin, a principal component of turmeric (Curcuma longa), has potential therapeutic activities against breast cancer through multiple signaling pathways. Increasing evidence indicates that curcumin reverses chemo-resistance and sensitizes cells to chemotherapy targeted therapy in cancer. To date, few studies have explored its antiproliferation effects resistance reversal antiestrogen-resistant In this study, we therefore investigated the efficacy alone combination with tamoxifen...
Abstract Pyruvate dehydrogenase kinase PDK1 is a metabolic enzyme responsible for switching glucose metabolism from mitochondrial oxidation to aerobic glycolysis in cancer cells, general hallmark of malignancy termed the Warburg effect. Herein we report identification JX06 as selective covalent inhibitor cells. forms disulfide bond with thiol group conserved cysteine residue (C240) based on recognition hydrophobic pocket adjacent ATP enzyme. Our investigations mechanism suggested that...
Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and responsible for aberrant glucose metabolism. We previously described bis(4-morpholinyl thiocarbonyl)-disulfide (JX06, 16) as the first covalent inhibitor of PDK1. Here, on basis scaffold 16, we identify two novel types disulfide-based PDK1 inhibitors. The potent analogue, 3a, effectively inhibits both at molecular (kinact/Ki = 4.17 × 103 M-1 s-1) cellular level (down to 0.1 μM). In contrast 3a is a...
Rodents respond to chronic high fat diet in at least two ways: some of them may readily gain body weight and become obese (termed obesity-prone, OP), others not obesity-resistant, OR). Transcriptomic metabonomic profiling OP OR rats has been conducted, showing sets significantly different phenotypic profiles response 16 weeks diet. We observed significant differences transcriptional expression nearly 80 genes, which are known be involved lipid metabolism, transport, ketone production. The...
Monocarboxylate transporter 4 (MCT4) is a cell membrane of lactate. Recent studies have shown that MCT4 over-expressed in various cancers; however, its role cancer maintenance and aggressiveness has not been fully demonstrated. This study investigated the oral squamous carcinoma (OSCC), found it highly expressed OSCC patients by using immunohistochemistry. Moreover, this over-expression was closely associated with tumor size, TNM classification, lymphatic metastasis, distant metastasis...
Glycolytic enzymes are known to play pivotal roles in cancer cell survival, yet their molecular mechanisms remain poorly understood. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that coordinates glycolysis, pentose phosphate pathway, and serine biosynthesis cells. Herein, we report PGAM1 required for homologous recombination (HR) repair of DNA double-strand breaks (DSBs) caused by DNA-damaging agents. Mechanistically, facilitates DSB end resection regulating the...
Stimulator of interferon gene (STING) is increasingly exploited for the potential in cancer immunotherapy, yet its mechanism activation remains not fully understood. Herein, we designed a novel STING agonist, designated as HB3089 that exhibits robust and durable anti-tumor activity tumor models across various types. Cryo-EM analysis reveals HB3089-bound human has structural changes similar to mutant V147L, constitutively activated identified patients with STING-associated vasculopathy onset...
A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed solid tumor therapy, as they many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 (sPD-1) from the extracellular domain blocks PD-1/PD-L1 interaction promote cancer immunology. Herein, we engineered a HER2-CAR-NK cell that co-expresses sPD-1 (designed sPD-1-CAR-NK cells) and...
Metabolomics has proven to be a valuable tool in gaining new insights into disease progression and prognosis, the specific metabolic alterations serum of recurrent chronic rhinosinusitis with nasal polyps (CRSwNP) patients remain unknown. This study aims explore metabolomic profiles CRSwNP identify potential predictive biomarkers.A prospective, single-center was conducted on prior endoscopic sinus surgery. Serum samples were subjected untargeted profiling. Patients followed up for over 2...
Triple-negative breast cancer (TNBC) is defined as a group of primary cancers lacking expression estrogen, progesterone, and human epidermal growth factor receptor-2 (HER-2) receptors, characterized by higher relapse rate lower survival compared with other subtypes. Due to lack identified targets molecular heterogeneity, conventional chemotherapy the only available option for treatment TNBC, but non-discordant positive therapeutic efficacy could not be achieved. Here, we demonstrated that...
Upregulation of pyruvate dehydrogenase kinase (PDHK) has been observed in a variety cancers. Inhibition PDHK offers an attractive opportunity for the development novel cancer therapies. To obtain inhibitors, we took advantage homology ATP-binding pocket between Heat Shock Protein 90 (HSP90) and PDHK, utilized 4,5-diarylisoxazole based HSP90 inhibitor structural design. Our efforts led to identification 5k that inhibited PDHK1 with IC50 value 17 nM, which, however, showed marginal cellular...
Activation of the stimulator interferon gene (STING) has emerged as an exciting immuno-oncology therapeutic strategy; however, first-generation STING agonists, cyclic dinucleotide (CDN) analogues, have suffered from many disadvantages and failed in clinical trials. Therefore, non-CDN small-molecule agonists are urgently needed. In view unique structure high potency dimeric amidobenzimidazole agonist 5, a structural elaboration was conducted by modifying several hotspots this scaffold....
Background Selective estrogen receptor modulators, such as tamoxifen, play a pivotal role in the treatment of luminal-type breast cancer. However, clinical applications, nearly half cancer patients are insensitive to small number whom have early recurrence or disease progression when receiving tamoxifen. The underlying mechanism this resistance has not been determined. ZNF703 is novel oncogene 15% cancers that harbor 8p12 amplifications. Therefore, goal our study was explore tamoxifen...
Oral squamous cell carcinoma (OSCC) comprises a subset of head and neck (HNSCC) with poor therapeutic outcomes high glycolytic dependency. Neoadjuvant chemotherapy regimens docetaxel, cisplatin 5-fluorouracil (TPF) are currently accepted as standard for HNSCC patients risk distant metastatic spread. However, the antitumor TPF neoadjuvant in remain controversial. This study investigated role lactate dehydrogenase B (LDHB), key enzyme catalyzing inter-conversion between pyruvate lactate,...
The stimulator of interferon genes (STING) protein is an important and promising innate immune target for tumor therapy. However, the instability agonists STING their tendency to cause systemic activation a hurdle. activator, cyclic di-adenosine monophosphate (CDA), produced by modified Escherichia coli Nissle 1917, shows high antitumor activity effectively reduces effects "off-target" caused pathway. In this study, we used synthetic biological approaches optimize translation levels...