Macrophages are essential immune cells involved in pathogen clearance, initiation and resolution of inflammation, and tissue repair across multiple organ systems. They exhibit remarkable phenotypic diversity, encompassing classical M1 and M2 subtypes-further subdivided into M2a, M2b, M2c, and M2d-as well as newly identified subsets such as Mreg, M4, Mox, and Mhem, each with distinct functional roles. Emerging evidence highlights cellular metabolism as a central regulator of macrophage phenotype and function. Distinct metabolic programs underpin the polarization of M1 and M2 macrophages in response to environmental cues, thereby critically influencing disease progression and tissue outcomes. Cardiovascular disease remains a leading cause of morbidity and mortality worldwide. In the heart, macrophages represent a dominant immune cell population and play integral roles in both pathological injury and tissue regeneration. This review provides a comprehensive overview of macrophage ontogeny, phenotypic heterogeneity, and metabolic reprogramming, with a particular focus on their roles in inflammatory heart diseases. We synthesize current findings on how metabolic pathways shape macrophage behavior and function within the cardiac microenvironment and discuss the therapeutic potential of targeting macrophage metabolism to modulate inflammation, promote repair, and improve clinical outcomes in cardiovascular disease.

Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia and reperfusion (I/R) models generated by clamping renal pedicles. However, it remains unclear whether TLR4 is causal in the kidney injury following global I/R induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The present study used wild‑type (C3H/HeN) and TLR4‑mutant (C3H/HeJ) mice to produce the CA/CPR model. CA was induced by injection of cold KCl and left untreated for different time periods. After resuscitation (72 h), the level of blood urea nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in renal tissue were assessed to evaluate the severity of acute kidney injury (AKI). The expression of TLR4, intercellular adhesion molecule‑1 (ICAM‑1), myeloperoxidase (MPO) and growth‑regulated oncogene‑β (GRO‑β) in kidney tissues was detected. The results demonstrated that the levels of Scr and BUN increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted in increased expression of TLR4, ICAM‑1, GRO‑β and MPO in a CA‑duration dependent manner. However, there was decreased expression of ICAM‑1, GRO‑β and MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were resistant to AKI as demonstrated by the minor changes in renal histology and function following CPR. In conclusion, mice suffered from AKI after successful CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its downstream signaling events that promote neutrophil infiltration via ICAM‑1 and GRO‑β may be important in mediating inflammatory responses to renal injury after CPR.

The sodium voltage-gated channel beta subunit 3 (SCN3B) plays a crucial role in electrically excitable cells and conduction tissue in the heart. Some previous studies have established that genetic modification in sodium voltage-channel genes encoding for the cardiac β-subunits, such as SCN1B, SCN2B, SCN3B and SCN4B, can result in atrial fibrillation (AF). In the current study, we identified two rare variants in 5′UTR (NM_018400.4: c.-324C>A, rs976125894 and NM_018400.4: c.-303C>T, rs1284768362) of SCN3B in two unrelated lone AF patients. Our further functional studies discovered that one of them, the A allele of c.-324C>A (rs976125894), can improve transcriptional activity and may raise SCN3B expression levels. The A allele of c.-324C>A (rs976125894) has higher transcriptional activity when it interacts with GATA4, as we confirmed transcription factor GATA4 is a regulator of SCN3B. To the best of our knowledge, the current study is the first to demonstrate that the gain-of-function mutation of SCN3B can produce AF and the first to link a mutation occurring in the non-coding 5′UTR region of SCN3B to lone AF. The work also offers empirical proof that GATA4 is a critical regulator of SCN3B gene regulation. Our findings may serve as an encyclopedia for AF susceptibility variants and can also provide insight into the investigation of the functional mechanisms behind AF variants discovered by genetic methods.

Gliomas are a type of highly heterogeneous and invasive central nervous system tumor. Traditional treatment methods have limited efficacy, and the prognosis for patients remains poor. Recent studies have revealed the crucial roles of several abnormal signaling pathways in the pathogenesis of gliomas, including the Receptor Tyrosine Kinase/Rat Sarcoma Virus Oncogene/Phosphatidylinositol-3-Kinase (RTK/RAS/PI3K) pathway, the Wingless-Related Integration Site/β-Catenin (Wnt/β-Catenin) pathway, the Hippo/YAP (Hippo/Yes-associated protein) pathway, and the Slit/Robo (Slit Guidance Ligands/Roundabout) signaling pathway. These pathways play extremely vital roles in tumor proliferation, invasion, and treatment resistance. This article comprehensively and systematically reviews the molecular mechanisms of these signaling pathways, deeply summarizing the research progress of various treatment strategies, including targeted inhibitors, gene therapy, and nanomedicine against them. Moreover, the combination of targeted therapy and personalized treatment regimens is expected to overcome the current treatment bottleneck and provide a more favorable survival prognosis for glioblastoma patients.

Diagnostic and treatment services for non‐communicable diseases (NCDs) face significant challenges in the context of the COVID‐19 pandemic. We used the Python programing language to extract and classify messages for help posted on the social networking platform microblog by NCD patients in the early stage of the COVID‐19 epidemic in Wuhan, China. We found of all NCD patients, the most frequently recorded conditions were basic chronic diseases (42.50%), acute critical diseases (35.53%), malignant tumours (15.10%), and patients requiring haemodialysis (6.79%). Regarding COVID‐19, 54.70% of patients reported suspected symptoms of infection, 32.01% were diagnosed with comorbidities, and 13.29% were non‐COVID‐19 patients. According to the analysis of the needs of the patients, 82.46% of the patients reported “No beds were available in the hospital”, 25.31% of patients needed nucleic acid tests. Our results confirmed it is difficult to meet the regular needs in the diagnosis and treatment of patients with NCDs. Effective prevention and management of NCDs in public health emergencies has become an urgent issue to be addressed. During the COVID‐19 epidemic, it is necessary to pay particular attention to the prevention and control of NCD patients, especially those with chronic disease. Governments and medical and health institutions at all levels should improve treatment mechanisms during major epidemics and ensure the uninterrupted treatment of patients with NCDs.