生理学报最新文献

N6-methyladenosine (m⁶A) is the most common type of RNA modification in eukaryotes, which affects intracellular RNA metabolism and controls gene expression of related pathophysiological processes through dynamic reversible regulation of methyltransferases, demethylases and m⁶A-binding proteins. In recent years, the involvement of m⁶A methylation in the study of neuropathic pain has become a hot topic, some new understandings have been emerging, and m⁶A methylation has become a potential biological target for the treatment of neuropathic pain. Therefore, this article reviews the role and regulation of m⁶A methylation in neuropathic pain, in order to provide new enlightenment for the drug development and treatment of neuropathic pain.

Adipose tissue holds a pivotal position in maintaining systemic energy homeostasis. Brown adipose tissue (BAT) expresses uncoupling protein 1 (UCP1), which is specialized in dissipating chemical energy as heat to maintain euthermia, a process called non-shivering thermogenesis. Conversely, white adipocyte (WAT) predominantly serves as the primary reservoir for energy storage, while also exhibiting endocrine activity by secreting various adipokines, thereby modulating systemic metabolism. Under the stimulation of cold exposure, physical activity and pharmacological intervention, WAT can occur as "browning" or "beiging", and transform into beige adipose tissue. The morphology and function of beige adipocyte are similar to brown adipocyte, both of which express higher levels of UCP1 and also have the function of thermogenesis. Thus, exploring methods to regulate the functional homeostasis of adipose tissue and its underlying molecular mechanisms hold promise for advancing preventative and therapeutic approaches against metabolic diseases. Exosomes, a subtype of extracellular vesicles (EVs) with a diameter of 40-100 nm, facilitate intercellular communication in obese individuals and exert significant influence on insulin resistance and impaired glucose tolerance within adipose tissue. These effects are primarily mediated by microRNA (miRNA) transported by exosomes. MiRNA, originating from various cellular sources, traverses between different cell types via EVs, thereby orchestrating reciprocal functional modulation among diverse tissues and organs. This review systematically summarized the research progress in exosomal miRNA-mediated regulation of adipose tissue functional homeostasis, with the aim of offering novel insights into the diagnosis and treatment of obesity and associated metabolic diseases.

The etiology of rheumatoid arthritis (RA), a chronic inflammatory systemic disease, remains unclear. It is characterized by symmetrical and invasive joint inflammation, primarily affecting distal small joints such as those in the hands and feet. This inflammation can lead to joint deformity and loss of function, and often accompanied by involvement of extra-articular organs like the lungs and heart. Currently, anti-rheumatic drugs only provide symptom improvement but have toxic side effects that require optimization. Therefore, it is crucial to thoroughly analyze the mechanisms underlying RA development for the identification of new drug targets. Programmed cell death (PCD) has been extensively studied in recent years and proved to be one of the key pathogenic factors in RA. Dysregulation of PCD is particularly evident in synoviocytes, immune cells, and osteocytes. This review summarizes various forms of PCD including apoptosis, NETosis, autophagy, pyroptosis, necroptosis, ferroptosis, cuproptosis, as well as their regulatory roles in fibroblast synoviocytes, immune cells and osteocytes. These findings hold significant theoretical implications for optimizing clinical treatment options for RA and developing new target drugs.

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.