Tumor heterogeneity and interaction with tumor microenvironment play a crucial role in neoadjuvant chemotherapy (NAC) resistance in breast cancer (BRCA). Unraveling this dynamic interaction may help uncover novel therapeutic targets. Here, dynamic changes in tumor states and cellular composition are systemically characterized using 175,825 single-cell transcriptomics from naïve and post-treatment biopsies of BRCA patients receiving NAC.
View Article and Find Full Text PDFAims: Impairment of nitric oxide (NO) production is a major cause of endothelial dysfunction and hypertension. ClC-5 Cl channel is abundantly expressed in the vascular endothelium. However, it remains unclear how it regulates endothelial function.
View Article and Find Full Text PDFThe formation of transcription regulatory complexes by the association of Smad4 with Smad2 and Smad3 (Smad2/3) is crucial in the canonical TGFβ pathway. Although the central requirement of Smad4 as a common mediator is emphasized in regulating TGFβ signaling, it is not obligatory for all responses. The role of Smad2/3 independently of Smad4 remains understudied.
View Article and Find Full Text PDFKu70, a DNA repair protein, binds to the damaged DNA ends and orchestrates the recruitment of other proteins to facilitate repair of DNA double-strand breaks. Besides its essential role in DNA repair, several studies have highlighted nonclassical functions of Ku70 in cellular processes. However, its function in immune homeostasis and antitumor immunity remains unknown.
View Article and Find Full Text PDFCell Rep Med
September 2024
Spatially resolved multi-omics revolutionizes cancer therapy by decoding the cellular and molecular heterogeneity of the tumor microenvironment through spatial coordinates. This commentary discusses the roles of spatial multi-omics in identifying precise therapeutic targets and predicting treatment responses while also highlighting the challenges that impede its integration into precision medicine.
View Article and Find Full Text PDFAlthough hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single-cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia-based intercellular communication hub consisting of malignant cells, ALCAM macrophages, and exhausted CD8 T cells around the tumor boundary.
View Article and Find Full Text PDFIntroduction: Coxsackievirus A6 (CVA6) has emerged as a significant pathogen responsible for severe cases of hand, foot, and mouth disease (HFMD). This study aims to delineate the demographic characteristics and analyze the viral evolution of severe HFMD associated with CVA6, thereby assisting in its surveillance and management.
Methods: In this investigation, 74 strains of CVA6 were isolated from samples collected from severe HFMD cases between 2012 and 2023.
Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets.
View Article and Find Full Text PDFOcular toxoplasmosis (OT) is an intraocular infection caused by the parasite OT is manifested as retinal choroiditis and is the most common infectious cause of posterior uveitis. Invasion of the retina by leads to disruption of the blood-ocular barrier and promotes the migration of immune cells to the ocular tissues. Cytokines such as IFN-γ and IL-1β are effective for controlling parasite growth, but excessive inflammatory responses can cause damage to the host.
View Article and Find Full Text PDFBackground: Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR.
View Article and Find Full Text PDFUnlabelled: Stromal cells are physiologically essential components of the tumor microenvironment (TME) that mediates tumor development and therapeutic resistance. Development of a logical and unified system for stromal cell type identification and characterization of corresponding functional properties could help design antitumor strategies that target stromal cells. Here, we performed a pan-cancer analysis of 214,972 nonimmune stromal cells using single-cell RNA sequencing from 258 patients across 16 cancer types and analyzed spatial transcriptomics from 16 patients across seven cancer types, including six patients receiving anti-PD-1 treatment.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
November 2023
Aging is associated with an increased risk of cardiovascular disease. Previous studies have demonstrated that compound 3 (C3), a derivative of marine compound xyloallenoide A isolated from the mangrove fungus sp. (no.
View Article and Find Full Text PDFEfficient strategies for HIV-1 cART-free virologic control are critical for ending the AIDS pandemic. The essential role of effector-memory CD8 T cells in controlling viremia and eliminating virus-infected cells has made them a promising target for vaccine development. It has been previously reported that PD-1-based DNA vaccination was effective in inducing polyfunctional effector-memory CD8 T cells for AIDS virus control for 2 years in rhesus monkeys.
View Article and Find Full Text PDFAims: Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation.
View Article and Find Full Text PDFAcute kidney injury (AKI) is associated with high morbidity and mortality. Our previous study has demonstrated that TMEM16A, a Ca-activated chloride channel, contributes to renal fibrosis progression in chronic kidney disease. However, whether TMEM16A is involved in AKI is still unknown.
View Article and Find Full Text PDFCircular RNAs (circRNAs) play important roles in the regulation of cancer. However, the clinical implications and regulatory networks of circRNAs in cancer patients receiving immune checkpoint blockades (ICB) have not been fully elucidated. Here, we characterize circRNA expression profiles in two independent cohorts of 157 ICB-treated advanced melanoma patients and reveal overall overexpression of circRNAs in ICB non-responders in both pre-treatment and early during therapy.
View Article and Find Full Text PDFBackground & Aims: The tumour microenvironment (TME) is a crucial mediator of cancer progression and therapeutic outcome. The TME subtype correlates with patient response to immunotherapy in multiple cancers. Most previous studies have focused on the role of different cellular components in the TME associated with immunotherapy efficacy.
View Article and Find Full Text PDFHere, sulfonated polyaniline (SPAN) was decorated on the surface of copper-based metal organic frame (HKUST-1) and the composite was functionalized by luminol to construct a chemiluminescence (CL) hybrids (SPAN/HKUST-1@Luminol). The as-prepared SPAN/HKUST-1@Luminol demonstrated a great dispersion and stability performance in aqueous solution. Moreover, the resultant SPAN/HKUST-1@Luminol hybrids exhibited extremely strong CL properties, and the CL quantum yield was 136 times higher than that of luminol.
View Article and Find Full Text PDFBackground: Discoidin Domain Receptor1 (DDR1) is a member of receptor tyrosine kinases (RTKs) which have been reported to be associated with idiopathic pulmonary fibrosis (IPF), but the mechanism remains unclear.
Methods: Bleomycin-induced IPF mice model was performed in this study, and two DDR1 inhibitors were administered in vivo, to investigate the role of DDR1 in IPF. Lentivirus mediated DDR1 stable Raw264.
Signal Transduct Target Ther
August 2022
Unlabelled: Alternative polyadenylation (APA) is an important posttranscriptional modification commonly involved in tumor development. However, the functional roles of APA in tumor immunity remain largely unknown. Here, we performed an in-depth analysis of the 3'UTR usage of protein-coding genes and tumor immune response in 10,303 tumor samples across 31 cancer types to develop the immune-related APA event (ImmAPA) score pipeline, an integrated algorithm to characterize the regulatory landscape of APA events in cancer immunity-related pathways.
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