Colchicine in acute coronary syndromes: the present and the possible future
Related Articles
Periodontitis impacts on thrombotic diseases: from clinical aspect to future therapeutic approaches
Periodontitis is a chronic inflammatory disease initiated by biofilm microorganisms and mediated by host immune imbalance. Uncontrolled periodontal infections are the leading cause of tooth loss in adults. Thrombotic diseases can lead to partial or complete obstruction of blood flow in the circulatory system, manifesting as organ or tissue ischemia and necrosis in patients with arterial thrombosis, and local edema, pain and circulatory instability in patients with venous thrombosis, which may lead to mortality or fatality in severe case. Recent studies found that periodontitis might enhance thrombosis through bacterial transmission or systemic inflammation by affecting platelet-immune cell interactions, as well as the coagulation, and periodontal therapy could have a prophylactic effect on patients with thrombotic diseases. In this review, we summarized clinical findings on the association between periodontitis and thrombotic diseases and discussed several novel prothrombotic periodontitis-related agents, and presented a perspective to emphasize the necessity of oral health management for people at high risk of thrombosis.
Exploring dietitians’ experiences caring for patients living with obesity in acute care: a qualitative study
Obesity is a modifiable risk factor associated with hospital-associated complications. Recent studies show there is a high prevalence of patients with obesity presenting to hospital and evidence indicates that people living with obesity should receive diet advice from a dietitian; however, patients often do not receive this care in acute settings.
Early cardio-oncology intervention in thoracic radiotherapy: prospective single-arm pilot study
While there is increasing recognition of the morbidity of cardiovascular disease in cancer survivors, including accelerated atherosclerosis following thoracic radiotherapy, patients are frequently under-optimized for cardiovascular risk.
Cancer cells sense solid stress to enhance metastasis by CKAP4 phase separation-mediated microtubule branching
Solid stress, originating from rigid and elastic components of extracellular matrix and cells, is a typical physical hallmark of tumors. Mounting evidence indicates that elevated solid stress drives metastasis and affects prognosis. However, the molecular mechanism of how cancer cells sense solid stress, thereby exacerbating malignancy, remains elusive. In this study, our clinical data suggest that elevated stress in metastatic solid tumors is highly associated with the expression of cytoskeleton-associated protein 4 (CKAP4). Intriguingly, CKAP4, as a sensitive intracellular mechanosensor, responds specifically to solid stress in a subset of studied tumor micro-environmental elements through liquid–liquid phase separation. These micron-scaled CKAP4 puncta adhere tightly onto microtubules and dramatically reorchestrate their curvature and branching to enhance cell spreading, which, as a result, boosts cancer cell motility and facilitates distant metastasis in vivo. Mechanistically, the intrinsically disordered region 1 (IDR1) of CKAP4 binds to microtubules, while IDR2 governs phase separation due to the Cav1.2-dependent calcium influx, which collectively remodels microtubules. These findings reveal an unprecedented mechanism of how cancer cells sense solid stress for cancer malignancy and bridge the gap between cancer physics and cancer cell biology.
Macrocarpal I induces immunogenic cell death and synergizes with immune checkpoint inhibition by targeting tubulin and PARP1 in colorectal cancer
Colorectal cancer (CRC) presents an obstacle to immunotherapy, primarily because most cases are microsatellite stable (MSS) tumors, which are often described as “cold tumors” with limited immunogenicity. Recent studies have indicated that several therapeutic approaches, such as chemotherapy and targeted therapies, can elicit immunogenic cell death (ICD) and stimulate immune responses. However, challenges such as target affinity and in vivo pharmacokinetics limit the efficacy and immune response of current targeted therapies. In this study, we demonstrate that Macrocarpal I is a potent inducer of ICD by activating the PERK/eIF2A/ATF4/CHOP signaling pathway. Furthermore, Macrocarpal I induces apoptosis and ferroptosis, both of which act as triggers for ICD. Mechanistically, Macrocarpal I directly targets TUBB2B and PARP1, disrupting microtubule polymerization and DNA repair processes. Importantly, treatment with Macrocarpal I enhances the anti-tumor immune response and augments responsiveness to anti-PD-1 therapy in an MC38 syngeneic mouse model of CRC.
Responses