生理学报最新文献

Cerebral ischemia/reperfusion injury (CIRI) refers to secondary damage caused by reperfusion of blood flow following ischemic stroke. Its mechanism is complex, involving mitochondrial energy metabolism disorders, Ca²⁺ overload, oxidative stress, apoptosis, inflammatory responses, excitatory amino acid toxicity, blood-brain barrier disruption, excessive NO synthesis, and cell necrosis etc. Mitochondrial-associated endoplasmic reticulum membranes (MAMs) are specialized regions of the endoplasmic reticulum that play crucial roles in various cellular processes, including regulation of mitochondrial morphology and activity, lipid metabolism, Ca²⁺ homeostasis, and cell viability. Existing research has confirmed that mitochondrial homeostasis, cell apoptosis, and endoplasmic reticulum stress are closely related to MAMs. This article summarizes the research progress on MAMs in recent years, reviews the biological functions of MAMs and the localization of tethering proteins, analyzes the signaling between mitochondria and the endoplasmic reticulum, explores the impact of MAMs tethering proteins interaction on Ca²⁺ signaling and cell viability during the pathophysiological process of CIRI, aiming to provide a theoretical basis for the treatment of CIRI.

Tumors pose a significant global health concern and have long been a challenging issue in the medical field. Given its treatment dilemma, it is urgent to explore novel prevention and treatment strategies. Bilirubin, as a natural endogenous antioxidant, has the ability to inhibit the production of free radicals in the body, thereby alleviating the damage caused by oxidative stress to the organism. In recent years, the therapeutic effects of bilirubin in diseases mediated by oxidative stress and metabolic disorders have gradually gained widespread attention, demonstrating its potential therapeutic value for a variety of diseases. With further research, significant progress has also been made in the study of bilirubin in the field of oncology, suggesting its potential important role in the occurrence, development, and treatment of tumors. This article aims to review and summarize the recent advances in the study of bilirubin in the field of oncology, in order to provide new insights and guidance for the future directions of tumor diagnosis, prevention, and treatment.

The study aimed to explore the effect and mechanism of resistance exercise (RE) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) mice. Six 8-week-old male m/m mice were used as control (Con) group, and db/db mice of the matched age were randomly divided into model control (db/db) group and db+RE group, with 6 mice in each group. The db+RE group was given 8 weeks of resistance climbing ladder exercise intervention. The fasting blood glucose and body weight of the mice were measured weekly. After the intervention, the spatial learning and memory of the mice were detected by Morris water maze, and the neuronal damage in the hippocampus of the mice was detected by Nissl staining. The protein expression levels of PSD93, PSD95, BDNF, CREB, p-CREB, IL-6, IL-1β, TNF-α, Iba-1, iNOS, CD206, Arg1, triggering receptor expressed on myeloid cells 2 (TREM2), NF-κB, p-STAT3, and STAT3 were detected by Western blot. The mRNA expression levels of inflammatory factors and TREM2 in hippocampus were evaluated by qRT-PCR, and the expression and localization of Iba-1, CD206, CD86, and TREM2 were determined by immunofluorescence staining. The results showed that the spatial learning and memory of the db/db group were significantly declined, the neurons in the hippocampus were damaged, the protein levels of PSD93, PSD95, BDNF, CD206, Arg1, TREM2 and the ratio of p-CREB/CREB were significantly down-regulated, the mRNA and protein expression levels of IL-6, IL-1β and TNF-α were significantly up-regulated, and the protein levels of iNOS, Iba-1, NF-κB and the ratio of p-STAT3/STAT3 were significantly increased compared with the Con group. However, the 8-week RE improved the spatial learning and memory of db/db mice, alleviated the damage of hippocampal neurons, promoted the polarization of M2 microglia, and inhibited the neuroinflammation. The above results suggest that RE can improve cognitive dysfunction in T2DM mice, and its mechanism may be related to regulating microglia polarization via TREM2/NF-κB/STAT3 signaling pathway.

The regulation of adipose tissue homeostasis is essential for maintaining energy and metabolism balance in the body. The peripheral nervous system plays a crucial role in this process. Previous related research primarily focused on the sympathetic nervous system and its release of norepinephrine, while recent attention has shifted to the field of adipose sensory nerves. Studies demonstrate that external stimuli can activate adipose sensory nerves through pathways involving transient receptor potential vanilloid-1 (TRPV1), adipokines, and fatty acids, thereby transmitting signals to the brain. Emerging techniques, such as adipose nerve imaging and denervation of tissues, have revealed the critical role of sensory nerves in the glucose and lipid metabolism, thermogenic function, and vascular regulation of adipose tissue. This article comprehensively reviews the latest research on the regulation and function of sensory nerves in adipose tissue, with a focus on the impact of metabolic diseases on adipose sensory nerves. This review discusses current issues and prospects on the mechanisms behind neural regulation in adipose tissue, hoping to contribute to a comprehensive understanding and providing directions for future research.

Dilated cardiomyopathy (DCM) is a non-ischemic cardiomyopathy with abnormal myocardial structure and function. It is challenging to construct human primary cardiac myocytes from DCM patients due to ethical constraints. In addition, animal models failed to adequately replicate the complexity of the human disease. The mechanism of DCM remains unclear. The emergence of human induced pluripotent stem cells (hiPSCs) provides a new tool for basic research in DCM. Researchers have produced hiPSCs-derived cardiomyocytes (hiPSC-CMs) and applied them to drug screening, leading to new insight into the pathomechanism and treatment in DCM. This review summarizes the research progress in the establishment, drug screening and mechanism research of DCM patient-specific hiPSC-CMs (DCM-hiPSC-CMs) model.

γ-Aminobutyric acid (GABA) neurotransmission alterations have been implicated to play a role in depression pathogenesis. While GABA_A receptor positive allosteric modulators are emerging as promising in clinical practice, their precise antidepressant mechanism remains to be further elucidated. The aim of the present study was to investigate the effects of LY-02, a novel compound derived from the metabolite of timosaponin, on depression in animals and its mechanism. The results of behavioral tests showed that LY-02 exhibited better antidepressant effects in both male C57BL/6 mice and Sprague Dawley (SD) rats. The results of cellular voltage clamp experiments showed that LY-02 enhanced GABA-mediated currents in HEK293T cells expressing recombinant α6β3δ subunit-containing GABA_A receptors. Electrophysiological recording from brain slices showed that LY-02 decreased the amplitude of spontaneous inhibitory postsynaptic current (sIPSC) and increased action potentials of pyramidal neurons in the medial prefrontal cortex (mPFC) of C57BL/6 mice. Western blot results showed that LY-02 dose-dependently up-regulated the protein expression levels of brain-derived neurotrophic factor (BDNF), tropomyosin related kinase B (TrkB) and postsynaptic density protein 95 (PSD-95) in mPFC of mice. The above results suggest that LY-02, as a positive modulator of GABA_A receptors, reduces inhibitory neurotransmission in pyramidal neurons. It further activates the BDNF/TrkB signaling pathway, thus exerting antidepressant effects. It suggests that LY-02 is a potential novel therapeutic agent for depression treatment.

Mitochondria play an important role in pressure overload-induced cardiac hypertrophy. The present study aimed to investigate the role of mitochondrial transient receptor potential vanilloid 3 (TRPV3) in myocardial hypertrophy. A 0.7 mm diameter U-shaped silver clip was used to clamp the abdominal aorta of Sprague Dawley (SD) rats and establish an animal model of abdominal aortic constriction (AAC). Rat H9C2 myocardial cells were treated with angiotensin II (Ang II) to establish a hypertrophic myocardial cell model, and TRPV3 expression was knocked down using TRPV3 small interfering RNA (siRNA). JC-1 probe was used to detect mitochondrial membrane potential (MMP). DHE probe was used to detect ROS generation. Enzyme activities of mitochondrial respiratory chain complex I and III and ATP production were detected by assay kits. Immunofluorescence staining was used to detect TRPV3 expression in H9C2 cells. Western blot was used to detect the protein expression levels of β-myosin heavy chain (β-MHC), mitochondrial TRPV3 and mitochondrial NOX4. The results showed that, in the rat AAC model heart tissue and H9C2 cells treated with Ang II, the protein expression levels of β-MHC, mitochondrial TRPV3 and mitochondrial NOX4 were up-regulated, MMP was decreased, ROS generation was increased, mitochondrial respiratory chain complex I and III enzyme activities were decreased, and ATP production was reduced. After knocking down mitochondrial TRPV3 in H9C2 cells, the protein expression levels of β-MHC and mitochondrial NOX4 were down-regulated, MMP was increased, ROS generation was decreased, mitochondrial respiratory chain complex I and III enzyme activities were increased, and ATP production was increased. These results suggest that mitochondrial TRPV3 in cardiomyocytes exacerbates mitochondrial dysfunction by up-regulating NOX4, thereby participating in the process of pressure overload-induced myocardial hypertrophy.

Obstructive sleep apnea (OSA) affects quality of life and health in nearly 1 billion patients all over the world. With aging society, OSA increases the risk of Alzheimer's disease and leads to severe cognitive impairment. Chronic intermittent hypoxia (CIH), the core pathological mechanism of OSA, may induce synaptic plasticity damage and cognitive impairment, and decrease learning and memory and attention ability. However, the molecular mechanism underlying OSA is still not fully understood. And, there is no targeted treatment strategy for cognitive impairment in patients with OSA. Firstly, the correlation between OSA and cognitive dysfunction was summarized in this review. Secondly, the molecular mechanism of CIH-induced cognitive impairment was elucidated from the perspectives of synaptic plasticity damage, oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, mitochondrial dysfunction and autophagy. Finally, the current treatment strategy for cognitive impairment in patients with OSA was summarized.

Oligodendrocyte precursor cells (OPCs) are recognized as the progenitors responsible for the generation of oligodendrocytes, which play a critical role in myelination of central nervous system. In addition, in demyelinating diseases, such as brain trauma, ischemia, and multiple sclerosis, OPCs are also found in demyelinated regions, but fail to differentiate into mature oligodendrocytes and remyelinate. From traditional view, OPC is victim of immune response. However, recent studies have shed light on immune associated OPCs (imOPCs), which are induced by interferon γ (IFN-γ), and interleukin 17 (IL-17), and are involved in the innate and adaptive immune activation. By expressing multiple natural immune pattern recognition receptors, such as Toll-like receptors, imOPCs can phagocytose myelin debris for antigen presentation. Furthermore, imOPCs can also secrete various inflammatory and chemotactic factors to regulate the differentiation of Th0 cells and the recruitment of NK cells, granulocytes and macrophages. Thus, it is of great importance to explore the immunoregulatory function of OPCs to elucidate the mechanisms and treatments of demyelinating diseases.

Elevated human metabolism during recovery is associated with increased excess post-exercise oxygen consumption (EPOC). EPOC is linearly related to exercise duration and exponentially related to exercise intensity. It is commonly believed that near-maximal intensity interval training prompts the body to produce greater EPOC. This review focuses on the origin and development of high-intensity interval training (HIIT), analyzes its concept, classification and function, and discusses its effects on human EPOC. HIIT promotes a significant increase in EPOC during the fast recovery period, whereas the changes of EPOC during the slow recovery period are still inconclusive; Sprint interval training (SIT) promotes a significant increase in EPOC throughout the whole recovery period. Compared with HIIT, the body's energy expenditure and oxygen uptake (VO₂) increase significantly during moderate-intensity continuous training (MICT), but the total energy expenditure and VO₂ during exercise and 24 h of recovery period are similar between the two types of exercises, indicating that greater EPOC is generated during the recovery period of HIIT. The mechanisms by which interval training improves EPOC include increasing lung ventilation and catecholamine secretion, accelerating systemic circulation, increasing body temperature, promoting glycogen resynthesis, rapid recruitment of fast twitch muscle fibers and uncoupling of mitochondrial respiration, up-regulating hypoxia inducible factor-1 alpha and skeletal muscle protein, as well as improving intestinal flora.