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The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui Department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina School of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

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Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration Research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei college of Pharmacy and First Clinical Medical college Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National Drug Clinical Trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

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Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

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Neural Regeneration Research 2025年第3期20卷 695-714页

作者： Beibei Wu Yuqing Liu Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng Department of Integrated traditional chinese&Western medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina Yangsheng college of traditional chinese medicine Guizhou University of Traditional Chinese MedicineGuiyangGuizhou ProvinceChina Qinhuangdao Shanhaiguan Pharmaceutical Co. LtdQinhuangdaoHebei ProvinceChina National Clinical Research Center for Mental Disorder The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary *** amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease *** abnormalities are commonly observed in patients with Alzheimer's *** liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's ***,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's *** this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol ***,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

关键词： ABCA1 Alzheimer's disease amyloid-beta apolipoprotein E cholesterol metabolism liver liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid

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Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

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Neural Regeneration Research 2025年第8期20卷 2245-2263页

作者： Run Song Shiyi Yin Jiannan Wu Junqiang Yan Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Neuromolecular Biology Laboratory The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and ***,excessive activation of regulated cell death may lead to the progression of aging-related *** review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related ***,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative *** forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein *** review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and *** instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis ***,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to *** insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death *** conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关键词： apoptosis autophagy cuproptosis disulfidptosis ferroptosis necroptosis neurodegenerative disease neurological aging diseases PANoptosis pyroptosis

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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina college of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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Cohort study on the treatment of BRAF V600E mutant metastatic colorectal cancer with integrated chinese and western medicine

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World Journal of Clinical Oncology 2025年第1期16卷 25-33页

作者： Jiang-Yu Bian Yu-Fang Feng Wen-Ting He Tong Zhang Department of Oncology Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China Department of Oncology The Fourth Clinical Medical College of Xinjiang Medical UniversityUrumqi 830001China Department of Oncology Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical UniversityUrumqi 830001China

BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor *** the previous cohort study on mCRC conducted by our team,it was observed that integrated chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal ***,we further explored the survival benefits in the population with BRAF V600E mutant *** To evaluate the efficacy of integrated chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal *** A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan hospital of China Academy of chinese Medical Sciences and traditional chinese medicine hospital of Xinjiang Uygur Autonomous Region from January 2016 to December *** patients were divided into two *** A total of 34 cases were included,with 23 in chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,*** analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(Pchinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.

关键词： Metastatic colorectal cancer BRAF V600E mutation Integrated chinese and Western medicine Cohort study

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Mechanism of action of Linggui Zhugan Decoction in treating non-alcoholic fatty liver disease using untargeted metabolomics approach

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traditional medicine Research 2025年第2期10卷 65-76页

作者： Huan Pei Ren-Lin Li Xin-Ran Song Qian-Qian Wan Yu-Ming Wang Han-Zhou Li Wei-Quan Xu Jia-Bao Liao Wei-Bo Wen Jing Miao Huan-Tian Cui School of Basic medicine Yunnan University of Chinese MedicineKunming 650599China School Clinical Medical college Yunnan University of Chinese MedicineKunming 650599China First School of Clinical medicine Yunnan University of Chinese MedicineKunming 650599China School of Integrative chinese and Western medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pharmacy Tianjin Second People's HospitalTianjin 300192China

Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver *** studies showed that metabolic dysfunction can promote NAFLD *** Zhugan Decoction(LGZGD)has therapeutic effects on *** mechanism of LGZGD still remains *** study was to examine the impact of LGZGD on the metabolic processes involved in the development of ***:A mice model of NAFLD was treated with *** therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of ***,this study also evaluated the influence of LGZGD on liver inflammation and oxidative ***:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD *** improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the *** metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate *** RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.

关键词： NAFLD LGZGD untargeted metabolomics glycerophospholipid metabolism citrate cycle

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Unraveling the mechanism of action of Shangxia Liangji formula for treating insomnia:a metabolomics and network pharmacology approach

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traditional medicine Research 2025年第2期10卷 16-29页

作者： Xia-Jie Quan Hao Liang Yong-Hong Tang Li Jiang Xiong-Ying Ji Feng-Ying Zhang Ping Zhang Bo Ouyang Department of Information The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Neurology The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of Gastroscopy The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China Department of traditional chinese medicine The Affiliated Nanhua HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421002China

Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of ***,the specific mechanism of action of SXLJF remains ***:The mouse model of insomnia was established by intraperitoneal injection of ***-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive *** open field test and pentobarbital-induced sleeping test were ***-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating ***,key targets were validated using ***:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep *** and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of ***,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,***-qPCR results supported the role of TH in the mechanism of SXLJF in treating ***:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.

关键词： Shangxia Liangji formula insomnia metabolomics network pharmacology tyrosine hydroxylase tyrosine metabolism

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Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi Ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The Clinical Medical college Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The Second Clinical Medical college Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

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Deciphering the molecular mechanisms of Simiaowan in the treatment of hyperuricemia: in vivo and in silico approaches

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traditional medicine Research 2025年第2期10卷 37-54页

作者： Yong-Chang Zeng Jun-Hong Wu Dan-Dan Xu Kang He Chang-Qing Liu Li-Fei Song Zheng-Zhi Wu Qian-Qian Jiang Shao-Yu Liang Department of Neurology The First Affiliated Hospital of Shenzhen UniversityShenzhen 518020China Pharmaceutical Department The Affiliated TCM Hospital of Guangzhou Medical UniversityGuangzhou 510000China School of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyang 550025China Guangzhou Zeli Medical Technology Co. Ltd.Guangzhou 510700China

Background:Simiaowan(SMW),a well-known traditional chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for ***,the bioactive components and underlying mechanisms have not been *** objective of this study was to identify the active components and potential mechanisms of SMW by integrating pharmacological experimentation,serum pharmacochemistry,network pharmacology and molecular ***:HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were used to evaluate the pharmacodynamic effects of ***-Q-Exactive-MS/MS was employed to detect the bioactive components present in SMW-containing *** pharmacology and molecular docking were utilized to elucidate the potential targets and underlying ***:SMW effectively ameliorated HUA rats via the inhibition of uric acid(UA)production,promotion of UA excretion,improvement of lipid and glucose metabolic abnormalities,antioxidant,anti-inflammatory and anti-insulin resistance effects.A total of 73 compounds detected in SMW-containing serum were identified as potential active components,with alkaloids,flavonoids,organic acids,and terpenoids emerging as the primary active *** 203 corresponding targets were obtained as SMW anti-HUA/gout targets,which mainly participated in apoptosis,insulin resistance,TNF,PI3K-Akt,HIF-1,NF-κB,MAPK,IL-17 and TLR signaling *** docking indicated that active compounds(***,phellodendrine,quercetin,formononetin,ferulic acid)had superior binding abilities to the key targets(*** carrier family 22 member 12(URAT1),solute carrier family 22 member 6(OAT1),ATP-binding cassette sub-family G member 2(ABCG2),solute carrier family 2,facilitated glucose transporter member 9(GLUT9),xanthine dehydrogenase/oxidase(XDH),transcription factor p65(RELA),toll-like receptor 4(TLR4),prostaglandin G/H synthase 2(PTGS2),caspase-3(CASP3),insulin(INS)).Conclusion:S

关键词： hyperuricemia network pharmacology serum pharmacochemistry Simiaowan UPLC-Q-Exactive-MS/MS

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