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The Journal of Clinical Investigation
Scopus
ISSN 0021-9738 · American Society for Clinical Investigation · 3.000 artikel di indeks
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Artikel Jurnal
Targeting immune checkpoint LAIR1 with antibody blockade or 3-in-1 CAR T cells enhances antitumor response
Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME) and dampen the immune response, negatively affecting patient survival. Therefore, targeting TAMs could address the limitations of current cancer treatments. However, drug development in this area remains limited…
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Artikel Jurnal
Gene therapy via CRISPR/Cas9-mediated Cxcr4 disease allele inactivation reverses leukopenia in WHIM mice
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is an immunodeficiency caused by autosomal dominant hyperfunctional mutations in chemokine receptor CXCR4 that promote panleukopenia due to BM retention. We previously reported a preclinical gene therapy protocol involving…
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Artikel Jurnal
Comprehensive genomic profiling of triple-negative breast cancer metastases identifies role of PKD1 in immunotherapy resistance
The multi-omics data represented by genomic data from patients with metastatic triple-negative breast cancer (TNBC) is crucial for precision treatment, yet data on genomic alterations in metastatic cohorts and Chinese populations remains limited. We performed targeted sequencing of 296 metastatic…
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Artikel Jurnal
Activin A secretion by muscle-repairing macrophages induces heterotopic ossification in mice
The immune system is not only essential for host defense, but it is also involved in tissue maintenance and disease pathogenesis. Macrophages play a key role in tissue repair, fibrosis, and tumorigenesis, but the mechanisms underlying their multifunctionality have not been fully explored. Here, we…
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Artikel Jurnal
Molecular stress and neurovascular injury in the diabetic retina
Diabetic retinopathy (DR), the most common microvascular complication in patients with diabetes mellitus (DM), is a leading cause of vision loss worldwide. Sustained hyperglycemia plays a central role in promoting DR. However, tight glycemic control does not prevent — and indeed sometimes worsens —…
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Artikel Jurnal
Poly(ADP-ribose) glycohydrolase enforces p21 degradation via dePARylation to promote gastric cancer progression
Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination…
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Artikel Jurnal
Lysophosphatidic acid–mediated NF-κB activation promotes FOXC2 expression essential for lymphatic valve development
The lymphatic system maintains tissue fluid balance, and FOXC2 mutations cause lymphoedema-distichiasis syndrome, which is characterized by lymphatic valve defects. Although oscillatory shear stress regulates FOXC2 expression, other extracellular regulators remain unclear. In this study, we…
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Artikel Jurnal
T cell receptor–engineered T cells targeting the TP53R248Q neoantigen elicit antitumor effects in human cancer models
Malignant tumors with TP53 mutations exhibit poor therapeutic outcomes and high recurrence rates. T cell receptor–based (TCR-based) T cell therapy shows great promise for targeting intracellular cancer neoantigens. However, the immunogenic potential of TP53 hotspot mutations remains poorly…
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Artikel Jurnal
Macrophage-rich niches regulate T cell dynamics at the liver invasive margin during gallbladder cancer progression
Liver invasion is one of the most frequent events in the progression of gallbladder cancer (GBC). However, the cellular and pathological role of the tumor-liver–interface microenvironment in liver invasion is still enigmatic. Here, we applied single-cell and spatial transcriptomics to…
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Artikel Jurnal
α-Ketoglutarate protects against cartilage damage via epigenetically driven metabolic reprogramming in osteoarthritis models
The link between glutaminolysis and osteoarthritis (OA) has only recently begun to be elucidated. Here, we report the association of obesity- and injury-induced cartilage damage with impaired glutaminolysis in chondrocytes. Defective glutaminolysis triggered the onset and progression of OA, with…
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Artikel Jurnal
The changing landscape of urothelial carcinoma: on the edge of a paradigm shift
Urothelial cancers of the urinary tract are the fourth most common malignancy in men, with a shifting demographic affecting younger patients and an increasing incidence in females. In this Review, we discuss recent discoveries and paradigm-shifting clinical trials that impact all stages of…
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Artikel Jurnal
Tumor-intrinsic chromatin programs enforce immune evasion in glioblastoma
Immunotherapy has shown limited efficacy in glioblastoma (GBM), reflecting profound immune evasion and an immunosuppressive microenvironment. In this Commentary, we highlight recent work by Zhang and colleagues identifying the transcription factor OLIG2 as a central mediator of immune evasion in…
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A midbrain–cortical circuit mediated by a claustrum neuronal ensemble orchestrates drug-paired context memory processing
Drug-associated environmental cues can trigger drug-seeking behavior and precipitate relapse. In this study, we determined that the claustrum (CL) connects the ventral tegmental area (VTA) with the medial prefrontal cortex (mPFC), forming the VTA–CL–mPFC circuit. Using a methamphetamine (METH)…
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Artikel Jurnal
IFN signaling is associated with radiotherapy response in malignant peripheral nerve sheath tumors
Patients with malignant peripheral nerve sheath tumors (MPNSTs) have poor outcomes despite multimodal treatment with surgery, radiation, and systemic therapy. The responses to radiotherapy (RT) are mixed, and the biologic mechanisms underlying this heterogeneity in the radiation response of MPNSTs…
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Artikel Jurnal
MRE11 deacetylation by SIRT2 promotes DNA binding to facilitate DNA end resection and ATM-dependent signaling
MRE11, a breast tumor suppressor and component of the MRE11-RAD50-NBS1 complex, plays a critical role in DNA end resection and initiation of ataxia-telangiectasia mutation–dependent (ATM-dependent) DNA damage signaling. However, the precise mechanisms governing MRE11 function in the DNA damage…
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Artikel Jurnal
IFN signaling at the nexus of the radiotherapy response in malignant peripheral nerve sheath tumors
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that constitute a major cause of mortality in individuals with neurofibromatosis type 1 (NF-1) and exhibit highly variable responses to radiotherapy. In this issue of the JCI, Zhu and colleagues integrated functional…
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Artikel Jurnal
Hepatic steatosis in humans is associated with preserved glucagon action on amino acid metabolism
BACKGROUND Amino acid (AA) concentrations are increased in prediabetes and diabetes. Since AAs stimulate glucagon secretion, which should then increase hepatic AA catabolism, it has been hypothesized that hepatic resistance (associated with hepatic fat content) to glucagon’s actions on AA…
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