BACKGROUND:The α7 nicotinic acetylcholine receptor is highly expressed in the cerebral cortex and hippocampus,and has been shown to play an important regulatory role in the pathological development of Alzheimer's disease,making it a potential therapeutic target for Alzheimer's disease.OBJECTIVE:To summarize the close relationship and interaction mechanism between α7 nicotinic acetylcholine receptor and Alzheimer's disease.METHODS:Retrieve relevant literature was searched in CNKI and PubMed databases using the search terms of"alpha7 nicotinic acetylcholine receptor,Alzheimer's disease,beta amyloid protein,agonist,positive allosteric modulator,antagonist"in Chinese and English,respectively.The search time was from database inception to July 2024.According to the inclusion criteria,the search results were accepted or excluded,and ultimately 83 articles that met the criteria were included for review.RESULTS AND CONCLUSION:The α7 nicotinic acetylcholine receptor interacts with β-amyloid protein to reduce the neurotoxicity of β-amyloid protein,such as promoting synaptic plasticity and rapid transmission of cholinergic synapses in Alzheimer's disease,alleviating central nervous system inflammation induced by β-amyloid protein,resisting neuronal apoptosis,and thus having a protective effect on the brain of patients with Alzheimer's disease.The α7 nicotinic acetylcholine receptor has great potential as a therapeutic target for Alzheimer's disease,but there are still a series of issues that need to be addressed,such as desensitization of α7 nicotinic acetylcholine receptor,stability of moderate activity,and gene polymorphism.Screening for drugs with high specificity,safety and multi-target binding action centered on the α7 nicotinic acetylcholine receptor will be a future direction for the treatment of Alzheimer's disease.

BACKGROUND:Studies have shown that tea polyphenols have anti-inflammatory effects on multiple organs,but there are few studies on the effects of tea polyphenols on central nervous system inflammation caused by exercise fatigue.OBJECTIVE:To explore the central anti-inflammatory effect and mechanism of tea polyphenols in exercise fatigue.METHODS:7-week-old male Kunming mice were divided into quiet control group,fatigue model group,and tea polyphenols group.In the fatigue model group,mice were given exhaustive swimming at one time.In the tea polyphenols group,tea polyphenols were injected into abdominal cavity half an hour before exhaustive swimming.The exhaustive swimming time in mice of fatigue model group and tea polyphenols group was recorded.Samples were taken from mice in each group after two hours of exhaustive swimming.The changes of brain tissue morphology and structure in each group were observed by hematoxylin-eosin staining.Western blot assay or real-time fluorescence quantitative polymerase chain reaction were used to detect the expression of inflammation-related factors,the activation of microglia,and the activation of STAT3/nuclear factor-κB p65 inflammatory pathway in the brain tissue of mice.Enzyme-linked immunosorbent assay was used to detect the levels of plasma inflammatory factors.RESULTS AND CONCLUSION:(1)Compared with the fatigue model group,the swimming exhaustion time of mice in the tea polyphenols group was significantly prolonged.(2)No abnormality was found in the hematoxylin-eosin staining results of brain tissues of mice in each group.(3)Compared with the quiet control group,the expression levels of inflammatory factors tumor necrosis factor α protein,interleukin-1β protein,M1 activated microglia marker-inducible nitric oxide synthase protein,nuclear factor-κB p65 protein and mRNA,and p-STAT3 protein and STAT3 mRNA in the fatigue model group were significantly increased,while the expression levels of anti-inflammatory factor interleukin-10 protein and M2 activated microglia marker-arginase 1 protein were significantly decreased.Compared with the fatigue model group,the inflammatory reaction,microglia types and signal molecules showed opposite obvious changes in the tea polyphenols group.(4)The expression levels of tumor necrosis factor α,interleukin 1β,interleukin-10 in peripheral plasma and brain tissue were consistent in mice of each group.(5)To sum up,exercise fatigue can trigger inflammatory reaction of nerve center,and tea polyphenols can alleviate this inflammatory reaction,and then enhance the fatigue resistance time of mice.The effects of exercise-induced fatigue and tea polyphenols on the inflammatory reaction in the brain may be completed through STAT3/nuclearfactor-κB p65 pathway.

BACKGROUND:Studies have shown that tea polyphenols have anti-inflammatory effects on multiple organs,but there are few studies on the effects of tea polyphenols on central nervous system inflammation caused by exercise fatigue.OBJECTIVE:To explore the central anti-inflammatory effect and mechanism of tea polyphenols in exercise fatigue.METHODS:7-week-old male Kunming mice were divided into quiet control group,fatigue model group,and tea polyphenols group.In the fatigue model group,mice were given exhaustive swimming at one time.In the tea polyphenols group,tea polyphenols were injected into abdominal cavity half an hour before exhaustive swimming.The exhaustive swimming time in mice of fatigue model group and tea polyphenols group was recorded.Samples were taken from mice in each group after two hours of exhaustive swimming.The changes of brain tissue morphology and structure in each group were observed by hematoxylin-eosin staining.Western blot assay or real-time fluorescence quantitative polymerase chain reaction were used to detect the expression of inflammation-related factors,the activation of microglia,and the activation of STAT3/nuclear factor-κB p65 inflammatory pathway in the brain tissue of mice.Enzyme-linked immunosorbent assay was used to detect the levels of plasma inflammatory factors.RESULTS AND CONCLUSION:(1)Compared with the fatigue model group,the swimming exhaustion time of mice in the tea polyphenols group was significantly prolonged.(2)No abnormality was found in the hematoxylin-eosin staining results of brain tissues of mice in each group.(3)Compared with the quiet control group,the expression levels of inflammatory factors tumor necrosis factor α protein,interleukin-1β protein,M1 activated microglia marker-inducible nitric oxide synthase protein,nuclear factor-κB p65 protein and mRNA,and p-STAT3 protein and STAT3 mRNA in the fatigue model group were significantly increased,while the expression levels of anti-inflammatory factor interleukin-10 protein and M2 activated microglia marker-arginase 1 protein were significantly decreased.Compared with the fatigue model group,the inflammatory reaction,microglia types and signal molecules showed opposite obvious changes in the tea polyphenols group.(4)The expression levels of tumor necrosis factor α,interleukin 1β,interleukin-10 in peripheral plasma and brain tissue were consistent in mice of each group.(5)To sum up,exercise fatigue can trigger inflammatory reaction of nerve center,and tea polyphenols can alleviate this inflammatory reaction,and then enhance the fatigue resistance time of mice.The effects of exercise-induced fatigue and tea polyphenols on the inflammatory reaction in the brain may be completed through STAT3/nuclearfactor-κB p65 pathway.

BACKGROUND:The α7 nicotinic acetylcholine receptor is highly expressed in the cerebral cortex and hippocampus,and has been shown to play an important regulatory role in the pathological development of Alzheimer's disease,making it a potential therapeutic target for Alzheimer's disease.OBJECTIVE:To summarize the close relationship and interaction mechanism between α7 nicotinic acetylcholine receptor and Alzheimer's disease.METHODS:Retrieve relevant literature was searched in CNKI and PubMed databases using the search terms of"alpha7 nicotinic acetylcholine receptor,Alzheimer's disease,beta amyloid protein,agonist,positive allosteric modulator,antagonist"in Chinese and English,respectively.The search time was from database inception to July 2024.According to the inclusion criteria,the search results were accepted or excluded,and ultimately 83 articles that met the criteria were included for review.RESULTS AND CONCLUSION:The α7 nicotinic acetylcholine receptor interacts with β-amyloid protein to reduce the neurotoxicity of β-amyloid protein,such as promoting synaptic plasticity and rapid transmission of cholinergic synapses in Alzheimer's disease,alleviating central nervous system inflammation induced by β-amyloid protein,resisting neuronal apoptosis,and thus having a protective effect on the brain of patients with Alzheimer's disease.The α7 nicotinic acetylcholine receptor has great potential as a therapeutic target for Alzheimer's disease,but there are still a series of issues that need to be addressed,such as desensitization of α7 nicotinic acetylcholine receptor,stability of moderate activity,and gene polymorphism.Screening for drugs with high specificity,safety and multi-target binding action centered on the α7 nicotinic acetylcholine receptor will be a future direction for the treatment of Alzheimer's disease.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

Objective: To analyze the effects of blue light on the formation of kidney stones. Methods: A total of 40 rats were randomly divided into 4 groups：A，B，C，and D，with 10 rats in each group.Rats in groups C and D were administered with a mixture of 10 g/L ethylene glycol，20 g/L ammonium chloride，and 100 g/L calcium gluconate via gavage (2 mL per mouse)，while rats in groups A and B received an equal volume of physiological saline via gavage.From the second day after gavage，rats in groups A and C were subjected to twice-daily blue light irradiation (one hour per session) as an intervention，while rats in groups B and D were subjected to fluorescent lamp irradiation using the same method.After 4 weeks of intervention，the 24-hour urine samples were collected，and the rats were then euthanized for the collection of blood and kidney tissue samples.Serum levels of antidiuretic hormone (ADH)，urinary Ca ，and urinary oxalate (Oxa) were measured.Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney tissues were detected using ELISA.Von Kossa staining was performed to observe pathological changes in kidney tissues and the presence of calcium salt crystals in the kidneys. Results: Compared with groups A and B，groups C and D showed higher accumulation of calcium salt crystals in renal tissues，as well as elevated levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues, additionally，the SOD level in renal tissues was lower (P<0.05).Compared with group D，group C exhibited higher accumulation of calcium salt crystals in renal tissues，along with increased levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues；conversely，the SOD level in renal tissues was lower (P<0.05). Conclusion: Blue light may increase the formation of kidney stones in rats by promoting the secretion of ADH in serum and oxidative stress in kidney tissues through the brain-kidney axis.

Objective To investigate the correlation between insulin resistance and interleukin-6 (IL-6), chemerin, total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low density lipoprotein cholesterol (LDL-C)/HDL-C ratio and insulin resistance in obese patients with type 2 diabetes mellitus (T2DM), and to provide scientific basis for T2DM prevention and control. Methods A total of 355 obese T2DM patients in Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine were selected from January 2021 to December 2023. IL-6, chemerin and lipids were detected, and the assessment of insulin resistance was conducted through the homeostasis model assessment of insulin resistance (HOMA-IR). Results Among the 355 obese T2DM patients, there were 280 cases of insulin resistance, with the incidence rate of 78.87%. The BMI, IL-6, chemerin, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C in the insulin resistance group were higher than those in the non-insulin resistance group (P<0.05). The above insulin resistant patients were divided into 4 subgroups by means of insulin resistance, and there were significant differences in BMI, IL-6, chemerin, and TG/HDL-C among the subgroups (P<0.05). IL-6, chemerin, and TG/HDL-C were positively correlated with HOMA-IR in obese T2DM patients (P<0.05), while TC/HDL-C and LDL-C/HDL-C had no significant correlation with HOMA-IR (P>0.05). BMI, IL-6, chemerin, and TG/HDL-C were all influencing factors of insulin resistance in obese T2DM patients (P<0.05). Conclusion IL-6, chemerin and TG/HDL-C are correlated with insulin resistance in obese patients with T2DM and are influencing factors for the occurrence of insulin resistance.

OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.

Astrocytes in the spinal dorsal horn (SDH) exhibit diverse reactive phenotypes under neuropathic conditions, yet the mechanisms driving this diversity and its implications in chronic pain remain unclear. Here, we report that spared nerve injury (SNI) induces marked upregulation of both complement component 3 (C3⁺, A1-like) and S100 calcium-binding protein A10 (S100A10⁺, A2-like) astrocyte subpopulations in the SDH, with elevated microglial cytokines including interleukin-1α, tumor necrosis factor-α, and complement component 1q. Transcriptomic, immunohistochemical, and Western blot analyses reveal co-activation of multiple reactive astrocyte states over a unidirectional shift toward an A1-like phenotype. Fibroblast growth factor 8 (FGF8), a neuroprotective factor via FGFR3, mitigated microglia-induced C3⁺ astrocyte reactivity in vitro and suppressed spinal C3 expression and mechanical allodynia following intrathecal administration in SNI mice. These findings reveal a microglia-astrocyte signaling axis that promotes A1 reactivity and position FGF8 as a promising therapeutic candidate for neuropathic pain by modulating astrocyte heterogeneity.
Animals ; Astrocytes/drug effects* ; Neuralgia/pathology* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Signal Transduction/physiology* ; Male ; Mice ; Microglia/drug effects* ; Fibroblast Growth Factor 8/pharmacology* ; Mice, Inbred C57BL ; Hyperalgesia/drug therapy* ; Spinal Cord/drug effects* ; Complement C3/metabolism* ; Spinal Cord Dorsal Horn/metabolism*