Titin (TTN), the largest protein by molecular weight in humans, extends beyond its roles in providing structural stability to the sarcomere and storing elastic potential energy. It also plays a crucial regulatory role in muscle hypertrophy and protein quality control. The protein complex encompassing the Z-disk, I-band, and M-line regions of TTN acts as a mechanosensor, dynamically modulating the transduction of myocellular hypertrophic signaling in response to mechanical tension. TTN induces skeletal muscle remodeling after exercise, mediating the repair and degradation of damaged TTN through protein protection and quality control mechanisms. Under appropriate mechanical stimulation, the TTN mechanosensory complex is activated, thereby triggering a series of hypertrophic responses. Conversely, following overload exercise, severely damaged TTN promotes its degradation through interactions of T-cap with MDM2, the proximal Ig region with calpain 1, and the N2A and M-line regions with calpain 3, as well as engagement of the MuRF1 binding site within the M-line domain. In this article, we delve into the role of the cytoskeletal protein TTN as a central signaling hub for skeletal muscle remodeling. Initially, the basic structure of TTN is elucidated, followed by an in-depth analysis of the mechanisms by which different regions contribute to muscle hypertrophy and protein quality control.

The aorta is one of the most important arteries in the human body. Although its basic vascular functions have been extensively studied, its multiple physiological roles as an independent organ have often been overlooked. Recent studies have shown that the aorta not only plays a central role in blood pressure maintenance, but also participates in key physiological processes such as metabolism, endocrinology, nervous system regulation, and immune stress. The unique structure and function of the aorta endow it with significant roles in a variety of physiological and pathological states. This article reviews the importance of the aorta as an independent organ and discusses its structural and functional uniqueness. Emphasis is placed on the metabolic and endocrine regulatory functions of aortic endothelial cells and smooth muscle cells, as well as the role of the aorta in neuroregulation and immune stress. The discussion of these research advances provides new perspectives for an in-depth understanding of the physiological and pathological functions of the aorta and offers potential research directions for future studies.

Ferroptosis is a form of programmed cell death associated with abnormal iron metabolism and excessive accumulation of lipid peroxides, characterized by unique biological processes and pathophysiological features. Lipid peroxidation represents the most fundamental mechanism underlying ferroptosis. Increasing evidence indicates that ferroptosis plays significant regulatory roles in the onset, development, and treatment of tumors.Induction of ferroptosis in tumor cells can effectively inhibit tumor growth and metastasis, and improve the therapeutic sensitivity of anti-tumor drugs. This article reviews the mechanisms by which lipid metabolic processes, such as the synthesis and remodeling of phospholipids,the storage and release of phospholipids,as well as the uptake and oxidation of fatty acids,regulate ferroptosis.It summarizes the effects of lipid metabolism-associated signaling pathways on ferroptosis and targeted therapeutic strategies, aiming to provide new insights for ferroptosis-associated basic research and clinical tumor therapy.

Sphingosine-1-phosphate (S1P), a metabolite of cell membrane sphingolipids, exerts its physiological functions by binding to G protein-coupled sphingosine-1-phosphate receptors (S1PRs) in various tissues of the human body. The S1P-S1PR signaling pathway plays a crucial role in mediating inflammatory responses, cardiac development, angiogenesis, as well as the migration, proliferation, and differentiation of immune cells. S1PRs have emerged as promising therapeutic targets for a variety of diseases, including autoimmune diseases, inflammation, cardiovascular diseases, and even cancer. However, the lack of in-depth understanding of S1PRs has hindered the development of clinical drugs. Therefore, this article reviews the current research status of S1PRs, focusing on S1PR-associated physiological functions, disease progression, and the development of representative drugs, with the aim of providing new insights for the clinical treatment of associated diseases.

Exosomes play an important role in intercellular communication by transferring substances such as proteins, lipids and nucleic acids between cells. The types and quantities of substances carried by exosomes vary depending on their cellular origin, resulting in heterogeneity in both the characteristics and functions of exosomes derived from different cell types. This heterogeneity underpins the basis of exosome function. Focusing on the heterogeneity of exosomes in terms of cellular origin and content, this article systematically elucidates the biological characteristics and functions of exosomes, providing a basis for future exosome screening and applications.

Diabetic kidney disease(DKD)is a severe microvascular complication of diabetes mellitus, representing the most common form of chronic kidney disease and a major cause of end-stage renal disease. Currently, available treatment options have notable limitations, including poor bioavailability, hepatorenal toxicity of oral medica-tions, and a lack of precise targeting. In recent years, nano-drug delivery systems (NDDS) have demonstrated significant potential in the treatment of kidney diseases. Nanocarriers are capable of targeting drugs to specific areas, addressing the issue of inadequate drug delivery to particular sites, and enhancing therapeutic efficacy. This article reviews the pathogenesis of DKD and the limitations of current treatment methods, while focusing on the application of NDDS in treating DKD. Finally, it presents the challenges and new visions for the future development of nanoplatforms, providing insights for achieving efficient targeted therapy for the kidney diseases.

Cardiovascular diseases significantly affect human health and represent an urgent public health issue that needs to be addressed.Reactive oxygen species (ROS) generated by mitochondrial metabolism are risk factors for the occurrence and progression of cardiovascular diseases. When mitochondrial function is impaired,excess ROS are generated.If the endogenous antioxidant system fails to eliminate the excess ROS,oxidative stress damage occurs,thereby compromising cardiovascular health.Therefore,improving mitochondrial function and reducing ROS through nutritional interventions has become a crucial approach to prevent and treat cardiovascular diseases.Mitoquinol mesylate (MitoQ),a mitochondria-targeted antioxidant,accumulates in the inner mitochondrial membrane,quenching mitochondrial ROS.This article reviews the molecular properties and mechanisms of action of MitoQ,as well as its benefits in improving cardiovascular diseases.Additionally,it compares the similarities and differences between MitoQ and coenzyme Q10 (CoQ10),providing a scientific basis for the future application of MitoQ in the treatment of cardiovascular diseases.

Circadian rhythm is a biological process that operates on an approximately 24-hour cycle, encompassing various physiological functions including blood pressure, heart rate, and body temperature. The normal circadian rhythm of blood pressure typically exhibits a characteristic “two-peak and one-valley” pattern, which is regulated by a combination of exogenous factors, including light exposure, exercise, and diet, as well as endogenous factors such as the autonomic nervous system, stress hormones, and clock genes. In recent years, lifestyle factors such as nocturnal light exposure, shift work, and jet lag have increasingly led to circadian rhythm disruption. The normal circadian rhythm of blood pressure is also often affected, contributing to circadian rhythm disorders of blood pressure. Numerous studies indicate that exercise can prevent cardiovascular diseases such as hypertension and heart failure, serving as an important non-pharmacological strategy to mitigate the disruptions in the circadian rhythm of blood pressure. Therefore, this review will take the factors influencing the circadian rhythm of blood pressure as a starting point, aiming to clarify the possible mechanisms through which exercise participates in regulating the blood pressure circadian rhythm, and to provide a theoretical basis for improving the circadian rhythm disorders of blood pressure through exercise.

The intestinal mucosal barrier is the first barrier between the intestine and the external environment, preventing harmful substances and pathogens from entering the internal environment and maintaining intestinal homeostasis. Bile acids, synthesized from cholesterol in the liver and subsequently converted into secondary bile acids by gut microbiota, interact with bile acid receptors and the gut microbiome, playing a key role in maintaining the homeostasis of the intestinal mucosal barrier. This review will elaborate on the role of bile acids and bile acid metabolism in the structure of the intestinal mucosal barrier, as well as the relationship between bile acids and intestinal diseases, aiming to provide insights for future strategies in the prevention and treatment of intestinal barrier dysfunction and associated intestinal diseases.

Metabolites produced by the gut microbiota play various physiological regulatory roles through interactions with the host and are closely related to human health. Imidazole propionate, a metabolite derived from histidine by the gut microbiota, has garnered significant attention in recent years due to its close association with chronic diseases such as type 2 diabetes and cardiovascular diseases. This article reviews the metabolic pathways of imidazole propionate, its correlation with metabolic and cardiovascular diseases, its mechanisms of action, and current methods for its detection and associated interventions. The aim is to provide a reference for the prevention and control of chronic diseases targeting imidazole propionate.

Post-stroke cognitive impairment (PSCI) is a common complication following stroke, posing a significant threat to patients' quality of life and survival time. Microglia, the major immune cells in the central nervous system, play a crucial role in the pathogenesis of PSCI by mediating immune responses and exerting neuroprotective effects. Research has indicated that triggering receptor expressed on myeloid cells 2 (TREM2), an immune response receptor predominantly expressed on microglia, is involved in the regulation of microglial number, phagocytosis, cytokine release, and metabolic functions. In this article, we elucidate the effect of TREM2-mediated regulation of microglial activity on PSCI, and explore the potential of TREM2 as a therapeutic target for the prevention and treatment of PSCI.

Lysosomal storage disorders (LSD) are a rare class of diseases caused by mutations in genes encoding lysosomal hydrolases, leading to metabolic disorders. These disorders arise from either the absence of functional lysosomal hydrolases or damage to the lysosomes. Impaired degradation of complex macromolecules leads to the accumulation of substrates in tissues and subsequent dysfunction of cells and organs. Current treatment options for LSDs primarily include enzyme replacement therapy, substrate reduction therapy, and chaperone therapy. However, most of these treatments do not cure the disease, but merely delay its progression. They necessitate continuous administration of medications, which can be financially burdensome, and often fail to effectively reach target sites due to various challenges, resulting in diminished therapeutic effects. Therefore, there is an urgent need for more effective and thorough treatment options. Extracellular vesicles (EVs) are naturally secreted components with potential applications in various diseases. However, their role and therapeutic potential in the context of LSDs remain unclear. This article summarizes current research progress on EVs in two common LSDs, Fabry disease and Gaucher disease, by reviewing literature from PubMed. It discusses biomarkers associated with EVs in the diagnosis and treatment of LSDs, as well as advancements in engineered EVs for therapeutic applications.

Periodontitis is a common oral disease and the leading cause of tooth loss in adults. The gingival epithelium is the first line of defense against external invasions. The occurrence and development of periodontitis are closely related to the invasion and destruction of the gingival epithelium by various pathogenic bacteria. Research has demonstrated that periodontitis-associated pathogens destroy the gingival epithelium,invade deep tissues,and trigger inflammatory responses through a series of virulence factors. Among them, Porphyromonas gingivalis is the main cause of periodontitis. This article reviews the regulatory effects of Porphyromonas gingivalis on the gingival epithelium, with the aim of providing a reference for the treatment of periodontitis.

Tumor immunotherapy has achieved impressive therapeutic effects in clinical practice and has attracted increasing attention. Among them, chimeric antigen receptor T (CAR-T) cell therapy has made breakthrough progress in the treatment of hematological malignancies. However, with prolonged exposure to tumor antigens, CAR-T cells may become exhausted in vivo. The exhaustion of CAR-T cells can lead to poor treatment efficacy or tumor recurrence. The mechanism of CAR-T cell exhaustion involves a series of processes, such as the expression of exhaustion-associated transcription factors, the role of the immunosuppressive tumor microenvironment, and the influence of CAR structure itself. Here, we summarize the process and underlying mechanisms of CAR-T cell exhaustion, as well as potential solutions to improve T cell exhaustion and enhance the efficacy of CAR-T cell therapy, with the aim of expanding the application of CAR-T cell therapy in tumor treatment.

MG53(mitsugumin 53) is a member of the tripartite motif (TRIM) protein family of E3 ubiquitin ligases,also known as TRIM72.MG53 is a cell membrane repair protein widely expressed in cardiac and skeletal muscles,capable of rapidly accumulating at the site of membrane injury, playing a crucial role in the repair of cardiac and skeletal muscle cell membranes. In recent years, numerous studies have found that MG53 participates in the myocardial protective effect of ischemic preconditioning and postconditioning, and mitigates myocardial ischemia-reperfusion injury. Moreover, it is expressed in various organs, promoting cell membrane repair under physiological or pathological conditions. However, MG53 overexpression leads to decreased expression of the ubiquitin-dependent insulin receptor, contributing to metabolic syndrome and diabetic heart disease. This article reviews the recent advances in the physiological functions and associated mechanisms of MG53 protein, aiming to provide a reference for the clinical application of recombinant human mitsugumin53 (rhMG53).

Hyperuricemia(HUA) is a pathological condition characterized by elevated levels of uric acid in the blood,which can adversely affect female reproductive health by altering the functions of the uterus and ovaries.Epigenetic modifications, primarily influenced by environmental factors,regulate gene expression without changing the gene sequence,thereby affecting individual metabolism,and being transmitted to the offspring through epigenetic imprinting. The occurrence of HUA results from the interaction between genetic and environmental factors. Understanding the underlying epigenetic mechanisms is of great significance for effective prevention and treatment of HUA and its complications. This article discusses in detail the effects of maternal HUA on pregnancy complications,gestational metabolic syndrome,and offspring health. It summarizes the epigenetic regulatory mechanisms of HUA, aiming to elucidate the pathogenesis of HUA at the molecular level and provide new research insights for reducing maternal pregnancy risks.

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder characterized by classic clinical features including motor symptoms such as tremor, muscle rigidity, bradykinesia, and abnormal posture and gait, as well as a variety of non-motor symptoms. Mitochondrial dysfunction plays a crucial role in the pathogenesis of PD, propelling genes associated with mitochondrial function to the forefront of current research endeavors. Some gene mutations are closely related to the pathogenesis of PD. Mitochondrial-related PD pathogenic genes include genes involved in mitochondrial dynamics, mitochondrial DNA homeostasis, mitochondrial protein translation, the mitochondrial respiratory chain, and mitochondrial metabolism, participating in the regulation of mitochondrial function and mitochondrial quality control, ultimately leading to structural and functional abnormalities in mitochondria. This article provides an overview of the mitochondrial-related PD pathogenic genes that are directly or indirectly associated with the onset and development of PD. Through in-depth studies of the functions and mechanisms of these genes, it is hoped that better therapeutic methods and prevention strategies for PD can be identified.

Sarcopenia is an age-related, systemic skeletal muscle disease that severely affects the health and quality of life of the elderly, serving as one of the leading causes of disability and increased social burden among this population. The imbalance between protein synthesis and degradation is a primary pathogenic mechanism, in which the ubiquitin-proteasome system (UPS), particularly E3 ubiquitin ligases (E3s), plays a crucial role in regulating muscle protein degradation. This article elucidates and summarizes the impact and mechanisms of E3s in sarcopenia-associated muscle atrophy, aiming to provide novel insights for basic research, the identification of therapeutic targets, and the development of preventive strategies for sarcopenia.

Exosomes are extracellular vesicles secreted by cells into the extracellular space, carrying abundant biomolecules such as proteins, nucleic acids and metabolites. MicroRNAs(miRNAs) are non-coding RNA molecules that play important roles in cell differentiation, proliferation, and survival.Exercise can induce the secretion of exosomes,and promote the biological effects of the contained miRNAs.Recent studies have indicated a close relationship between exosomal miRNAs and chronic heart failure,exercise can alter the expression of exosomal miRNAs in body fluids and tissues.Exosomal miRNAs serve as biomarkers for the diagnosis and prognosis of heart failure,potentially ameliorating heart failure by inhibiting myocardial fibrosis,promoting myocardial mitochondrial function,and enhancing myocardial cell survival. Therefore,this article reviews the role of exosomal miRNAs in chronic heart failure and the mitochondrial mechanisms through which exercise improves chronic heart failure via exosomal miRNAs, offering a valuable basis for future diagnosis and treatment of heart failure.

Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a crucial regulator of mitochondrial biogenesis and oxidative metabolism, with its activity and expression linked to various diseases. In recent years, there has been a growing body of research on the relationship between PGC1α and cancer. The role of PGC1α in tumors exhibits significant heterogeneity, with both overexpression and underexpression of PGC1α reported to be associated with tumor occurrence, development, and prognosis, emphasizing its critical role in tumorigenesis and progression. Therefore, this article comprehensively reviews the classification, structure, function, activity regulation, and pro-carcinogenic and anti-carcinogenic effects of PGC1α, as well as its roles in oral cancer, aiming to provide a valuable theoretical reference for targeted energy metabolism therapy of malignant tumors.