Dysregulated glucose metabolism in diabetic wound macrophages impairs polarization toward the reparative M2 phenotype, leading to compromised innate immunity, chronic inflammation, and delayed wound healing. However, effective strategies to restore macrophage metabolic function remain limited. Here, inspired by vanadium’s potential to modulate glucose metabolism and the...
Visual hallucination (VH) is a common nonmotor symptom of Parkinson’s disease (PD). However, the lack of reliable animal models and quantitative assessment tools poses significant challenges for mechanism and intervention research in this area. Here, we developed a novel PD-related visual hallucination (PDVH) model by administering benzhexol hydrochloride, which can induce...
Sexual hormones play an important role in modulating disease outcome of COVID-19. The interplay between viral replication, host immune responses, pathology process and sexual hormone levels are complicated, and the underlying mechanisms remain exclusive. Here, we reveal the dose-dependent manner and multi-faceted role of the male hormone testosterone in hamster model of COVID-19...
Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in cancer treatment. Nevertheless, most patients receiving CAR T cells relapse within 5 years of treatment. CAR-mediated trogocytosis (CMT) is a potential tumor escape mechanism in which cell surface proteins transfer from tumor cells to CAR T cells. CMT results in the emergence of antigen-negative tumor...
Relapse remains the leading cause of mortality in acute myeloid leukemia (AML), largely due to the persistence of therapy-resistant leukemia stem cells (LSCs). However, surface determinants that sustain LSC function and disease aggressiveness remain incompletely defined. Here, we identify the tetraspanin CD81 as a regulator of LSC function, progression and treatment resistance in...
Hypoxia drives diabetic kidney disease (DKD) progression through Hypoxia Inducible Factor (HIF) signaling. The kidney’s cellular heterogeneity and complex architecture pose challenges for directly assessing the pharmacologic effects on kidney oxygenation and hypoxia-responsive pathways in vivo, such as treatment with SGLT2 inhibitors (SGLT2i), presumed to impact kidney...
Cardiovascular disease (CVD) predominantly affects elderly individuals and is the leading cause of morbidity, disability, and mortality worldwide. Systemic ageing, especially cardiovascular ageing, contributes to the development of CVD phenotypes and outcomes. Therefore, in this review, we innovatively summarize the five major etiologies and risk factors for cardiovascular ageing...
Acquired pure red cell aplasia (aPRCA) is rare and challenging to treat. We investigated the efficacy and safety of sirolimus plus roxadustat in patients with aPRCA (Chinese Clinical Trial Register number, ChiCTR2200065107). We enrolled 82 patients with aPRCA in this prospective single-arm, open-label, multicenter trial between October 2022 and January 2024. Treatment response...
Brain aging is accompanied by cognitive decline and an increased risk of neurodegenerative disease, with neuronal aging being a key causative factor. Studies have shown that the earliest damage to blood-brain barrier (BBB) integrity occurs in the hippocampus, leading to the abnormal accumulation of Fe²⁺;however, the mechanisms underlying subsequent neuronal aging remain unclear...
Immune-cold tumors fail to respond to immunotherapy due to insufficient lymphocyte infiltration within the tumor tissue. Increasing the objective response rate remains an urgent challenge. Here, we report the development of a monoclonal antibody (6C5) that specifically targets the membrane-proximal epitope of the receptor tyrosine kinase AXL and modulates antitumor immunity...
Tumor-derived extracellular vesicles (EVs) play crucial roles in facilitating the colonization and growth of metastatic cancer cells in distant organs. Nevertheless, the precise mechanisms by which EVs contribute to therapy-resistant cancer dissemination remain poorly understood. In the present study, we aim to investigate how EVs derived from lenvatinib-resistant (LR...
Endoplasmic reticulum (ER) stress is a key cellular mechanism that is important in the development of many diseases, including cancer. Since the discovery of the unfolded protein response (UPR), research has greatly improved our understanding of how ER stress affects cellular functions, especially protein folding and adaptation to stress. The UPR consists of three main branches...
Treatment options for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that progresses after CDK4/6 inhibitor (CDK4/6i) continue to evolve, and no single regimen has been established as the preferred standard of care. We conducted a phase 2 trial (SYSUCC-020, NCT05411380) to investigate the...
Esophageal cancer (EC), encompassing primarily esophageal squamous-cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), continues to pose a significant global health burden, which is largely due to delayed diagnosis and limited therapeutic efficacy. In this review, we synthesize current insights into key aspects of EC, including established risk factors, the stepwise...
Managing unresectable metastatic colorectal cancer (mCRC) requires a comprehensive strategy. While chemotherapy, anti-angiogenic, and anti-epidermal growth factor receptor (EGFR) agents are available, strategy trials are needed to optimize their use and sequencing. The STRATEGIC-1 phase III trial (NCT01910610) was designed to determine the optimal treatment sequence in patients...
Metastatic castration-resistant prostate cancer (mCRPC) after treatment with docetaxel and androgen receptor signaling inhibitors (ARSIs) has limited treatment options. Although enzalutamide has shown activity after abiraterone and docetaxel, robust evidence from randomized phase III trials is lacking. Deutenzalutamide, a novel derivative with slower metabolism and improved...
The potential of the immune system to decrease cancer progression is widely recognized and has led to the development of innovative anti-cancer immunotherapies. Here, we studied human macrophages derived from genetically engineered iPSCs (iMac) with angiotensin-converting enzyme (ACE) expression regulatable by a doxycycline (dox)-inducible promoter as a novel anti-cancer...
Immune modulatory vaccines (IMVs) are an emerging class of immunotherapies designed to expand anti-regulatory T cells (anti-Tregs) that selectively target immunosuppressive elements within the tumor microenvironment (TME). Unlike conventional cancer vaccines aimed at tumor-associated antigens on malignant cells, IMVs target tumor microenvironment antigens (TMAs), such as...
Chimeric antigen receptor (CAR)-based immunotherapies against solid tumors face two major hurdles, the “decoy effect” of shedding antigens that sequester CARs, and the limited persistence of immune effectors within the immunosuppressive tumor microenvironment. Here, we present a mechanistic approach to overcome these barriers by integrating a physiologically relevant screening...
Patients diagnosed with metastatic colorectal cancer (mCRC) face a constrained therapeutic landscape following the failure of initial treatment. This multicenter, single-arm, phase II trial (NCT06202001) aimed to assess the efficacy and safety of a novel second-line regimen comprising trifluridine/tipiracil (TAS-102), irinotecan, and bevacizumab. Patients with mCRC resistant to...
Tumors foster an immunosuppressive microenvironment to evade the antitumor immune response. However, the influence of intratumoral immunosuppressive steroids on tumor-infiltrating natural killer (NK) cells and their implications for effective immunotherapy has remained largely unexplored. Here, we report that the functional enrichment of glucocorticoid cortisol signaling in the...
Chemotherapy resistance remains a critical bottleneck limiting its clinical efficacy in small cell lung cancer (SCLC), with its core mechanisms and targeted intervention strategies urgently requiring breakthroughs. Our study revealed that the BMX (bone marrow tyrosine kinase on chromosome X)-E2F1 (E2F transcription factor 1) axis is a pivotal regulator of chemoresistance in SCLC...
In this phase 3 trial, penpulimab combined with chemotherapy was assessed against a regimen of placebo plus chemotherapy for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). 291 patients were randomised and allocated in a 1:1 ratio in order to receive penpulimab (n = 144; 200 mg) or placebo (n = 147; 200 mg), plus chemotherapy (cisplatin...