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The dopaminergic system and Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2495-2512页

作者： Yuhan Zhang Yuan Liang Yixue Gu International medical college Chongqing Medical UniversityChongqingChina college of pharmacy Chongqing Medical UniversityChongqingChina Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqingChina

Alzheimer's disease is a common neurodegenerative disorder in older *** its prevalence,its pathogenesis remains unclea *** addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this *** is a crucial catecholaminergic neurotransmitter in the human ***-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical *** r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive *** review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related *** aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

关键词： adverse drug reaction Alzheimer's disease catecholamine dopamine receptor dopamine receptor heterodimers dopaminergic system neurodegenerative disease neurotransmitter signaling pathways traditional Chinese medicine treatment

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

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Neural Regeneration Research 2025年第8期20卷 2420-2432页

作者： Lin Yin Yalan Xu Jie Mu Yu Leng Lei Ma Yu Zheng Ruizhi Li Yin Wang Peifeng Li Hai Zhu Dong Wang Jing Li Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina School of Basic Medicine Qingdao UniversityQingdaoShandong ProvinceChina college of Life Sciences and School of PharmacyMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina Department of Urology Qingdao Municipal Hospital Affiliated to Qingdao UniversityQingdaoShandong ProvinceChina

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding *** of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully *** has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic ***,the function of CNKSR2 in the cytoplasm remains to be *** this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of *** a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the *** also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker *** colocalization analysis confirmed the centrosomal localization of *** we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal *** manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and ***,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum *** findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

关键词： autism spectrum disorder centrosome CNKSR2 intellectual disability interactome mass spectrometry microtubule neurodevelopmental disease protein complexes protein-protein interactions

Evaluation of the therapeutic significance of Glehniae Radix polysaccharides on the ulcerative colitis through DSS-induced rat model

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Food Science and Human Wellness 2025年

作者： Jie Liu Xufang Geng Yuxin Yang Jiao Xu Haoran Feng Tianshuo Zhang Guangzhao Zhou Man Wang Changshun Wang Dongsheng Jia Yuting Chen Bin Cong Ding Zhao The Postdoctoral Mobile Station of Basic Medicine， Hebei medical university The Department of Pharmacognosy， School of pharmacy， Hebei medical university Hebei Key Laboratory of Forensic Medicine， college of Forensic Medicine， Hebei medical university

Glehniae Radix has a wide range of pharmaceutical applications， and research on its main components has mainly focused on coumarins， alkaloids， lignans， and flavonoids， while neglecting the research on polysaccharides. Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation， antioxidant， anti-inflammatory and other aspects. Herein， the rat model of ulcerative colitis (UC) was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide (GLP) from the perspectives of inflammatory factors， intestinal tissue morphology， and microflora changes. The polysaccharides are mainly composed of galacturonic acid， rhamnose， glucose， galactose， and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9， and GLP could downregulate the expression pro-inflammatory factors (interleukin-6， tumor necrosis factor-α， and interferon-γ) and significantly upregulate the expression of anti-inflammatory factor (interleukin-10). In addition， Glehniae Radix aqueous extract (GLA)， GLP with low dosage (GLPL) and GLP with high dosage (GLPH) could increase the number of goblet cells， enhance the integrity of crypt structure， and reverse the status of inflammatory infiltrating cells. Moreover， GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats， and appropriately downregulate Lachnospiraceae＿NK4A136＿group， thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment. Our findings not only be valuable as theoretical materials for the further clinical applications of GLP， but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.

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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

Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology Research 2025年第1期33卷 67-81页

作者： XIANG LI WENKE JIN LIFENG WU HUAN WANG XIN XIE WEI HUANG BO LIU State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

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(P<0.05).CONCLUSION Integrated Chinese 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

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

Engendered nanoparticles for treatment of brain tumors

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Oncology Research 2025年第1期33卷 15-26页

作者： SOROUSH SOLEYMANI MOHAMMAD DOROUDIAN MAHDIEH SOEZI ALI BELADI KIARASH ASGARI ASO MOBARAKSHAHI ARYANA AGHAEIPOUR RONAN MACLOUGHLIN Department of Cell and Molecular Biology School of Biological SciencesUniversity of LeicesterLeicesterLE17RHUK Department of Cell and Molecular Biology Faculty of Biological SciencesKharazmi UniversityTehran15719-14911Iran Cancer Epidemiology Research Center Aja University of Medical SciencesTehran14117-18541Iran medical Biotechnology Research Center Aja University of Medical SciencesTehran14117-18541Iran Department of Life Sciences Faculty of Natural SciencesImperial College LondonLondonSW72AZUK School of pharmacy and Biomolecular Sciences Royal College of Surgeons in Ireland(RCSI)DublinD02 YN77Ireland Research and Development Science and Emerging TechnologiesAerogen Ltd.Galway Business ParkGalwayH91 HE94Ireland School of pharmacy and Pharmaceutical Sciences Trinity CollegeDublinD02 PN40Ireland

Brain metastasis and primary glioblastoma multiforme represent the most common and lethal malignant brain *** median survival time is typically less than a year after *** of the major challenges in treating these cancers is the efficiency of the transport of drugs to the central nervous *** blood-brain barrier is cooperating with advanced stages of *** blood-brain barrier poses a significant challenge to delivering systemic medications to brain *** delivery systems have emerged as promising tools for effectively crossing this ***,the development of smart nanoparticles brings new hope for cancer diagnosis and *** nanoparticles improve drug delivery efficiency,allowing for the creation of targeted and stimuli-responsive delivery *** review highlights recent advancements in nanoparticle and smart nanoparticle technologies for brain cancer treatment,exploring the range of nanoparticles under development,their applications,targeting strategies,and the latest progress in enhancing transport across the blood-brain *** also addresses the ongoing challenges and potential benefits of these innovative approaches.

关键词： Nanoparticles Smart nanoparticles Stimuli responsive nanoparticles Targeted nanoparticles Blood-brain barrier(BBB) Brain cancer

An magnetic resonance-based plasma metabonomic investigation on abnormal Savda in different complicated diseases

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Journal of Traditional Chinese Medicine 2014年第2期34卷 166-172页

作者： Batur Mamtimin Mawlanjan Hizbulla Nazuk Kurbantay Li You Xinghai Yan Halmurat Upur college of pharmacy Xinjiang Medical University college of Traditional Chinese Medicine Xinjiang Medical University

OBJECTIVE： To provide existence of abnormal potential evidence for the Savda, we assessed host metabonomic responses and dynamic changes oc- curring in various diseases using 1H nuclear mag- netic resonance （NMR）-based metabonomics. METHODS： Plasma samples taken from patients with complicated diseases with abnormal Savda （n= 140, including 35 cases each of diabetes, asthma, breast cancer, and cervical carcinoma） and from healthy controls （n=35） were analyzed by ~H NMR （600 MHz）, and the spectral profiles were analyzed by multivariate analysis using orthogonal projec- tion to latent structure with discriminant analysis. RESULTS： Supervised modeling of the data provid- ed very good discrimination between patients and healthy controls. Compared with ,the healthy controls, the patient groups with different disease con- ditions displayed similar metabolic changes, characterized by lower creatine, creatinine, lactate, and amino acid levels （including isoleucine, leucine, va- line, alanine, and 1-methylhistidine） and higher lip- id levels （very low-density lipoproteins and unsatu- rated lipids）. Additionally, cancer patients （breast and cervical） showed decreased myo-inositol, a-glucose, and 13-glucose, and increased pyruvate and carnitine in plasma. CONCLUSION： The data indicate that decreased ox- idative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of complicated diseas- es, which may be related to the formation of abnor- mal Savda.

关键词： Metabonomics Magnetic resonancespectroscopy Abnormal Savda