Hypoxia-inducible factors (HIFs) are essential transcription factors that orchestrate cellular responses to oxygen deprivation. HIF-1α, as an unstable subunit of HIF-1, is usually hydroxylated by prolyl hydroxylase domain enzymes under normoxic conditions, leading to ubiquitination and proteasomal degradation, thereby keeping low levels. Instead of hypoxia, sometimes even in normoxia, HIF-1α translocates into the nucleus, dimerizes with HIF-1β to generate HIF-1, and then activates genes involved in adaptive responses such as angiogenesis, metabolic reprogramming, and cellular survival, which presents new challenges and insights into its role in cellular processes. Thus, the review delves into the mechanisms by which HIF-1 maintains its stability under normoxia including but not limited to giving insights into transcriptional, translational, as well as posttranslational regulation to underscore the pivotal role of HIF-1 in cellular adaptation and malignancy. Moreover, HIF-1 is extensively involved in cancer and cardiovascular diseases and potentially serves as a bridge between them. An overview of HIF-1-related drugs that are approved or in clinical trials is summarized, highlighting their potential capacity for targeting HIF-1 in cancer and cardiovascular toxicity related to cancer treatment. The review provides a comprehensive insight into HIF-1’s regulatory mechanism and paves the way for future research and therapeutic development.

Cardiovascular diseases (CVDs) remain the leading cause of global mortality, yet their pathogenesis has not been fully elucidated, particularly regarding the role of abnormal energy metabolism. Major outstanding questions pertain to the dynamic regulation of metabolic reprogramming and its complex interplay with mitochondrial dysfunction. Previous studies have demonstrated that the heart, as a high-energy-demand organ, relies on the dynamic equilibrium of substrates such as fatty acid (FA) and glucose to sustain adenosine triphosphate (ATP) production. Metabolic disturbances—characterized by suppressed FA oxidation and aberrant activation of glycolysis—directly contribute to the pathological progression of various CVDs, including heart failure (HF), atherosclerosis, and myocardial infarction(MI), through mechanisms involving oxidative stress, inflammatory responses, and an energy crisis. This review systematically examines the core pathways of cardiac energy metabolism (e.g., mitochondrial oxidative phosphorylation (OXPHOS), regulation of glucose and lipid metabolism) and their dysregulation in disease states, while evaluating intervention strategies targeting metabolic pathways, such as mitochondrial function enhancement and substrate utilization modulation. Future research directions emphasize the integration of metabolomics with clinical translational studies to comprehensively decipher the multidimensional regulation of metabolic networks, thereby facilitating the development of novel precision therapeutic targets.

Cancer invasion and metastasis are critical factors that influence patient prognosis. Carbonic anhydrase IX (CA IX) and carbonic anhydrase XII (CA XII) are key regulators of hypoxia and pH homeostasis in the tumor microenvironment (TME). It has been verified that both CA IX and CA XII play significant roles in promoting tumor metastasis in recent years, but most of the literature tends to treat them as separate entities rather than exploring their synergistic effects. This review provides a comprehensive overview of the roles of CA IX and CA XII in tumor invasion and metastasis, along with their clinical applications, including their spatial distribution characteristics, molecular mechanisms that facilitate tumor metastasis, and their potential for clinical translation. Moreover, this review incorporates the classical tumor core–invasive front model to propose a metabolic coupling model of CA IX and CA XII, offering a fresh perspective on precision therapies that target tumor metabolism. By emphasizing the metabolic coupling between these two molecules, this review offers new insights distinct from previous studies and highlights the clinical therapeutic potential of simultaneously targeting both during treatment. It sheds new light on future research and clinical applications, aiming to enhance the prognosis of cancer patients through innovative therapeutic strategies.

As one of the most prevalent malignant neoplasms among women globally, the optimization of therapeutic strategies for breast cancer has perpetually been a research hotspot. The tumor microenvironment (TME) is of paramount importance in the progression of breast cancer, among which the extracellular matrix (ECM) and hypoxia are two crucial factors. The alterations of these two factors are predominantly regulated by the Hippo signaling pathway, which promotes tumor invasiveness, metastasis, therapeutic resistance, and susceptibility. Hence, this review focuses on the Hippo pathway in breast cancer, specifically, how the ECM and hypoxia impact the biological traits and therapeutic responses of breast cancer. Moreover, the role of miRNAs in modulating ECM constituents was investigated, and hsa-miR-33b-3p was identified as a potential therapeutic target for breast cancer. The review provides theoretical foundations and potential therapeutic direction for clinical treatment strategies in breast cancer, with the aspiration of attaining more precise and effective treatment alternatives in the future.

Cardiovascular diseases (CVDs) are recognized as a major global public health challenge whose prevention and management have long been a focus of scientific investigation. Panax ginseng Meyer (ginseng), as a herbal remedy with a long historical usage, is extensively utilized in the field of complementary and alternative medicine. This review was based on the Web of Science core collection, searching and screening for relevant studies on “ginseng” and “cardiovascular disease”. Subsequently, the target literature records were analyzed and visualized using CiteSpace, Scimago Graphica, Bibliometrix R software package, and Microsoft Excel. This review summarized the research trajectory of ginseng in the prevention and treatment of CVDs from 1998 to 2025, analyzed its development characteristics, research hotspots and emerging frontiers, in order to provide new methods for the application of herbal medicine and promote clinical translation and the integration of complementary and alternative medicine with modern medical practice, demonstrating the enormous potential of ginseng in the prevention and treatment of CVDs.