The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Hypoxic-ischemic encephalopathy(HIE)is a major cause of newborn mortality and childhood disability.Despite hypothermia treat-ment being the current standard method,it has its limitations and often produces unsatisfactory out-comes.Additionally,due to time and equipment constraints,hypothermia treatment cannot be promptly administered,leading to high mortality rates or varying levels of neurological impairments even after treatment.Hence,the exploration of al-ternative and effective treatment methods for HIE has become a challenging and highly researched topic in the field of neonatology.Research has shown that HIE induces intricate changes in the neurological system at the physiological,cellular,and molecular levels.Circular RNA(circRNA)exhib-its high expression in the central nervous system and plays a role in regulating physiological and pathophysiological processes.Therefore,circRNA holds promise as a potential therapeutic target for HIE.This article provides a comprehensive over-view of the regulatory effects of circRNA on differ-ent types of neural cells in HIE,aiming to offer new theoretical foundations for the treatment of HIE.

Hypoxic-ischemic encephalopathy(HIE)is a major cause of newborn mortality and childhood disability.Despite hypothermia treat-ment being the current standard method,it has its limitations and often produces unsatisfactory out-comes.Additionally,due to time and equipment constraints,hypothermia treatment cannot be promptly administered,leading to high mortality rates or varying levels of neurological impairments even after treatment.Hence,the exploration of al-ternative and effective treatment methods for HIE has become a challenging and highly researched topic in the field of neonatology.Research has shown that HIE induces intricate changes in the neurological system at the physiological,cellular,and molecular levels.Circular RNA(circRNA)exhib-its high expression in the central nervous system and plays a role in regulating physiological and pathophysiological processes.Therefore,circRNA holds promise as a potential therapeutic target for HIE.This article provides a comprehensive over-view of the regulatory effects of circRNA on differ-ent types of neural cells in HIE,aiming to offer new theoretical foundations for the treatment of HIE.

Objective:To investigate the associations of onset age, diabetes duration, and glycated hemoglobin (HbA1c) levels with ischemic stroke risk in type 2 diabetes patients.Methods:The participants were from Comprehensive Research on the Prevention and Control of the Diabetes in Jiangsu Province. The study used data from baseline survey from December 2013 to January 2014 and follow-up until December 31, 2021. After excluding the participants who had been diagnosed with stroke at baseline survey and those with incomplete information on onset age, diabetes duration, and HbA1c level, a total of 17 576 type 2 diabetes patients were included. Cox proportional hazard model was used to calculate the hazard ratio ( HR) and 95% CI of onset age, diabetes duration, and HbA1c level for ischemic stroke. Results:During the median follow-up time of 8.02 years, 2 622 ischemic stroke cases were registered. Multivariate Cox proportional risk regression model showed that a 5-year increase in type 2 diabetes onset age was significantly associated with a 5% decreased risk for ischemic stroke ( HR=0.95, 95% CI: 0.92-0.99). A 5-year increase in diabetes duration was associated with a 5% increased risk for ischemic stroke ( HR=1.05, 95% CI: 1.02-1.10). Higher HbA1c (per 1 standard deviation increase: HR=1.17, 95% CI: 1.13-1.21) was associated with an increased risk for ischemic stroke. Conclusion:The earlier onset age of diabetes, longer diabetes duration, and high levels of HbA1c are associated with an increased risk for ischemic stroke in type 2 diabetes patients.

To investigate the associations of serum gamma-glutamyl transferase (GGT) levels with the risk of cardiovascular disease (CVD) and its subtypes in patients with type 2 diabetes mellitus (T2DM) in Jiangsu Province.Methods:The participants were enrolled in the Comprehensive Research project regarding 'Prevention and Control of Diabetes' in Jiangsu Province. The baseline survey was conducted from 2013 to 2014, and follow-up until December 31, 2021. After excluding the participants who self-reported with chronic liver disease/stroke/coronary heart disease at baseline survey and those with incomplete information on GGT, a total of 16 147 T2DM patients were included in the final analysis. Cox proportional hazard regression models were used to calculate the hazard ratio ( HR) and their 95% CI of GGT for CVD, myocardial infarction, and stroke. Restricted cubic spline models were applied to analyze the dose-response relationship between GGT and the risk of CVD and its subtypes. Results:During the median follow-up time of 8.02 years, 2 860 CVD cases were registered, including 196 cases of myocardial infarction and 2 730 cases of stroke. Multivariate Cox proportional risk regression model indicated that compared to the lowest serum GGT level group, the highest GGT level group had a 24% increased risk of CVD ( HR=1.24, 95% CI: 1.09-1.41) and a 23% increased risk of stroke ( HR=1.23, 95% CI: 1.08-1.40). The restricted cubic spline model showed a nonlinear dose-response relationship between GGT and the risk of CVD, myocardial infarction, and stroke in T2DM patients. Conclusions:High levels of GGT may be associated with an increased risk of cardiovascular disease in T2DM patients, which needs further exploration and validation in future clinical practice.

Objective: To investigate the awareness of relevant knowledge and influencing factors among high-risk populations for chronic obstructive pulmonary disease (COPD), so as to provide the reference for improving COPD awareness and disease prevention. Methods: The COPD high-risk populations were selected from community health service centers of Nanfeng, Jingang, Daxin and Fenghuang townships in Zhangjiagang City, Jiangsu Province from 2020 to 2022. Basic information, lifestyle, health status and awareness of relevant knowledge were collected through questionnaire surveys. Anxiety symptoms was assessed using the Generalized Anxiety Disorder Scale. Factors affecting the awareness of relevant knowledge among COPD high-risk populations were identified using a structural equation model. Results: A total of 2 078 COPD high-risk populations were surveyed, including 1 111 females (53.53%) and 967 males (46.47%), and had a mean age of (60.85±6.59) years. The total awareness score of relevant knowledge among high-risk populations for COPD was (6.33±2.59) points, with an awareness rate of 72.18%. Structural equation model analysis showed that age, annual household income, educational level, smoking, respiratory diseases, occupational exposure and anxiety symptoms had direct effects on the awareness of relevant knowledge, with direct effect values of -0.057 (95%CI: -0.099 to -0.014), 0.048 (95%CI: 0.005 to 0.090), 0.162 (95%CI: 0.117 to 0.204), 0.060 (95%CI: 0.018 to 0.096), 0.055 (95%CI: 0.021 to 0.088), 0.139 (95%CI: 0.107 to 0.170) and -0.172 (95%CI: -0.209 to -0.135), respectively; while age, gender, and occupational exposure also had indirect effects on the awareness of relevant knowledge, with indirect effect values of -0.069 (95%CI: -0.090 to -0.051), -0.084 (95%CI: -0.113 to -0.053), and 0.007 (95%CI: 0.003 to 0.014), respectively. Conclusion The awareness of relevant knowledge among COPD high-risk populations is associated with age, gender, annual household income, educational level, smoking, respiratory diseases, occupational exposure and anxiety symptoms.

Hypoxic-ischemic encephalopathy(HIE)is a major cause of newborn mortality and childhood disability.Despite hypothermia treat-ment being the current standard method,it has its limitations and often produces unsatisfactory out-comes.Additionally,due to time and equipment constraints,hypothermia treatment cannot be promptly administered,leading to high mortality rates or varying levels of neurological impairments even after treatment.Hence,the exploration of al-ternative and effective treatment methods for HIE has become a challenging and highly researched topic in the field of neonatology.Research has shown that HIE induces intricate changes in the neurological system at the physiological,cellular,and molecular levels.Circular RNA(circRNA)exhib-its high expression in the central nervous system and plays a role in regulating physiological and pathophysiological processes.Therefore,circRNA holds promise as a potential therapeutic target for HIE.This article provides a comprehensive over-view of the regulatory effects of circRNA on differ-ent types of neural cells in HIE,aiming to offer new theoretical foundations for the treatment of HIE.

Hypoxic-ischemic encephalopathy(HIE)is a major cause of newborn mortality and childhood disability.Despite hypothermia treat-ment being the current standard method,it has its limitations and often produces unsatisfactory out-comes.Additionally,due to time and equipment constraints,hypothermia treatment cannot be promptly administered,leading to high mortality rates or varying levels of neurological impairments even after treatment.Hence,the exploration of al-ternative and effective treatment methods for HIE has become a challenging and highly researched topic in the field of neonatology.Research has shown that HIE induces intricate changes in the neurological system at the physiological,cellular,and molecular levels.Circular RNA(circRNA)exhib-its high expression in the central nervous system and plays a role in regulating physiological and pathophysiological processes.Therefore,circRNA holds promise as a potential therapeutic target for HIE.This article provides a comprehensive over-view of the regulatory effects of circRNA on differ-ent types of neural cells in HIE,aiming to offer new theoretical foundations for the treatment of HIE.

Hypoxic-ischemic encephalopathy(HIE)is a major cause of newborn mortality and childhood disability.Despite hypothermia treat-ment being the current standard method,it has its limitations and often produces unsatisfactory out-comes.Additionally,due to time and equipment constraints,hypothermia treatment cannot be promptly administered,leading to high mortality rates or varying levels of neurological impairments even after treatment.Hence,the exploration of al-ternative and effective treatment methods for HIE has become a challenging and highly researched topic in the field of neonatology.Research has shown that HIE induces intricate changes in the neurological system at the physiological,cellular,and molecular levels.Circular RNA(circRNA)exhib-its high expression in the central nervous system and plays a role in regulating physiological and pathophysiological processes.Therefore,circRNA holds promise as a potential therapeutic target for HIE.This article provides a comprehensive over-view of the regulatory effects of circRNA on differ-ent types of neural cells in HIE,aiming to offer new theoretical foundations for the treatment of HIE.