1.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
2.Guidelines for vaccination of kidney transplant candidates and recipients in China
Jian Zhang ; Jun Lin ; Weijie Zhang ; Xiaoming Ding ; Xiaopeng Hu ; Wujun Xue
Organ Transplantation 2025;16(2):177-190
In order to further standardize the vaccination of kidney transplant candidates and recipients in China, the Branch of Organ Transplantation of Chinese Medical Association has organized experts in kidney transplantation and infectious diseases. Based on the "Vaccination of Solid Organ Transplant Candidates and Recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice", and in combination with the clinical reality of infectious diseases and vaccination after organ transplantation in China, as well as referring to relevant recommendations from home and abroad in recent years, these guidelines are formulated from aspects such as epidemiology, types of vaccines, vaccination principles, target population, and specific vaccine administration. The "Guidelines for Vaccination of Kidney Transplant Candidates and Recipients in China" aims to provide theoretical reference for medical workers in the field of kidney transplantation in China, regarding the vaccination of kidney transplant candidates and recipients. It is expected to better guide the vaccination of kidney transplant candidates and recipients, reduce the risk of postoperative infection, and improve survival outcomes.
3.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
4.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
5.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
6.Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study
Yu Meng TIAN ; Wei Sen ZHANG ; Chao Qiang JIANG ; Feng ZHU ; Ya Li JIN ; Shiu Lun Au YEUNG ; Jiao WANG ; Kar Keung CHENG ; Tai Hing LAM ; Lin XU
Diabetes & Metabolism Journal 2025;49(1):60-79
Background:
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods:
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results:
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.
7.Effect of lncRNA MANCR on Proliferation, Migration, and Epithelial Mesenchymal Transition of Gastric Cancer Cells by Regulating miR-150-5p/GPNMB Axis
Chao LI ; Shihui WANG ; Jie LIN ; Fanke WANG ; Rui ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):135-142
ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA (lncRNA MANCR) on the proliferation,migration, and epithelial mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating the microRNA-50-5p (miR-150-5p)/non-metastatic melanoprotein B (GPNMB) axis. MethodsThe mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro, and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group (routine culture),sh-NC group (with sh-NC transfected),sh-MANCR group (with sh-MANCR transfected),sh-MANCR + anti-NC group (with sh-MANCR and anti-NC both transfected),and sh-MANCR + anti-miR-150-5p group (with sh-MANCR and anti-miR-150-5p both transfected). The mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin,N-cadherin,Vimentin, and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue,and the expression of miR-150-5p was lower than that in adjacent tissue (P<0.05). Compared with that in GES-1,lncRNA MANCR expression in BGC-823 cells was increased (P<0.05). Compared with those in the sh-NC group and control group,the EdU-positive cell rate,migration number,invasion number,the mRNA expressions of lncRNA MANCR and GPNMB, and the expressions of protein,N-cadherin protein, and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ,and the protein expressions of miR-150-5p and E-cadherin were higher (P<0.05). Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group,the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate,migration number,invasion number,mRNA expressions of GPNMB, and expressions of protein,N-cadherin protein, and Vimentin protein were increased (P<0.05). lncRNA MANCR could target the negative regulation of miR-150-5p,and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation,migration, and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.
8.Effect of lncRNA MANCR on Proliferation, Migration, and Epithelial Mesenchymal Transition of Gastric Cancer Cells by Regulating miR-150-5p/GPNMB Axis
Chao LI ; Shihui WANG ; Jie LIN ; Fanke WANG ; Rui ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):135-142
ObjectiveTo investigate the effects of mitotically-associated long non-coding RNA (lncRNA MANCR) on the proliferation,migration, and epithelial mesenchymal transition (EMT) of gastric cancer (GC) cells by regulating the microRNA-50-5p (miR-150-5p)/non-metastatic melanoprotein B (GPNMB) axis. MethodsThe mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in 42 cases of GC tissue and adjacent tissue resected during surgery in the First Hospital of Hebei Medical University from June 2022 to September 2023 were detected by Real-time PCR. Human gastric mucosal epithelial cells GES-1 and human GC cells BGC-823 were cultured in vitro, and their lncRNA MANCR expression was detected. BGC-823 cells were randomly separated into control group (routine culture),sh-NC group (with sh-NC transfected),sh-MANCR group (with sh-MANCR transfected),sh-MANCR + anti-NC group (with sh-MANCR and anti-NC both transfected),and sh-MANCR + anti-miR-150-5p group (with sh-MANCR and anti-miR-150-5p both transfected). The mRNA expressions of lncRNA MANCR,miR-150-5p, and GPNMB in the BGC-823 cells of all groups were analyzed. EdU staining was used to detect the proliferation of BGC-823 cells. Transwell assay was used to detect the migration and invasion of BGC-823 cells. The expressions of EMT-related proteins E-cadherin,N-cadherin,Vimentin, and GPNMB were detected by Western blot. The interactions between lncRNA MANCR and miR-150-5p and between miR-150-5p and GPNMB were analyzed by dual luciferase reporter assay. ResultsThe mRNA expressions of lncRNA MANCR and GPNMB in GC tissue were higher than those in adjacent tissue,and the expression of miR-150-5p was lower than that in adjacent tissue (P<0.05). Compared with that in GES-1,lncRNA MANCR expression in BGC-823 cells was increased (P<0.05). Compared with those in the sh-NC group and control group,the EdU-positive cell rate,migration number,invasion number,the mRNA expressions of lncRNA MANCR and GPNMB, and the expressions of protein,N-cadherin protein, and Vimentin protein in the BGC-823 cells in the sh-MANCR group were lower ,and the protein expressions of miR-150-5p and E-cadherin were higher (P<0.05). Compared with those in the sh-MANCR group and the sh-MANCR + anti-NC group,the protein expressions of miR-150-5p and E-cadherin in the sh-MANCR + anti-miR-150-5p group were decreased. The EdU-positive cell rate,migration number,invasion number,mRNA expressions of GPNMB, and expressions of protein,N-cadherin protein, and Vimentin protein were increased (P<0.05). lncRNA MANCR could target the negative regulation of miR-150-5p,and miR-150-5p could target the negative regulation of GPNMB. ConclusionKnockout of lncRNA MANCR can inhibit the proliferation,migration, and EMT of GC cells by regulating the miR-150-5p/GPNMB axis.
9.circFSCN1 regulates malignant behaviors of gastric cancer MGC803 cells via the miR-429/GPNMB axis
LI Chao ; WANG Shihui ; LIN Jie ; WANG Fanke ; ZHANG Rui
Chinese Journal of Cancer Biotherapy 2025;31(8):831-838
[摘 要] 目的:探究环状RNA肌动蛋白束蛋白1(circFSCN1)调节miR-429/非转移性黑色素蛋白B(GPNMB)轴对胃癌细胞恶性生物学行为的影响及机制。方法:收集2022年9月至2023年9月期间在河北医科大学第一医院手术切除的54例胃癌组织及相应癌旁组织,用qPCR法检测胃癌组织中circFSCN1、miR-429和GPNMB mRNA的表达。常规培养胃癌细胞MGC803,将其分为对照组、sh-NC组、sh-circFSCN1组、sh-circFSCN1 + anti-NC组、sh-circFSCN1 + anti-miR-429组。qPCR法各组MGC803细胞中circFSCN1、miR-429和GPNMB mRNA的表达。CCK-8法、克隆形成实验、Transwell实验和流式细胞术分别检测各组MGC803细胞的增殖、迁移、侵袭和凋亡。免疫荧光法检测各组细胞中GPNMB蛋白的表达。WB法检测各组MGC803细胞中PCNA、MMP-2、GPNMB、cleaved caspase-3蛋白的表达。双萤光素酶报告基因实验和RNA结合蛋白免疫共沉淀(RIP)实验验证circFSCN1与miR-429和miR-429与GPNMB之间的结合调控关系。结果:circFSCN1、GPNMB mRNA在胃癌组织中均呈高表达(均P < 0.05),miR-429呈低表达(P < 0.05)。敲减circFSCN1可促进miR-429表达,抑制GPNMB mRNA表达,抑制miR-429则可促进GPNMB mRNA表达。敲减circFSCN1可显著抑制MGC803细胞的增殖、迁移、侵袭能力,并促进其凋亡,抑制miR-429可部分逆转敲减circFSCN1的作用。敲减circFSCN1可抑制MGC803细胞中PCNA、MMP-2和GPNMB蛋白表达,抑制cleaved caspase-3蛋白表达,抑制miR-429可部分逆转敲减circFSCN1的作用。circFSCN1与miR-429和miR-429与GPNMB mRNA之间存在靶向结合负向调控关系。结论:敲减circFSCN1通过miR-429/GPNMB轴抑制胃癌细胞的恶性生物学行为,circFSCN1是胃癌潜在的治疗靶点。
10.Effects of LINC00894 regulating miR-205-5p/GPNMB axis on proliferation, migration, and invasion of gastric cancer cells
LI Chao ; WANG Shihui ; LIN Jie ; WANG Fanke ; ZHANG Rui
Chinese Journal of Cancer Biotherapy 2025;32(9):912-919
[摘 要] 目的:探究长链非编码RNA00894(LINC00894)调节微小RNA-205-5p(miR-205-5p)/糖蛋白非转移性黑色素瘤蛋白B(GPNMB)轴对胃癌细胞恶性生物学行为的影响。方法:收集2022年11月至2023年9月在河北医科大学第一医院手术切除的25例胃癌组织及相应癌旁组织,常规培养BGC823细胞,随机将其分为对照组、sh-NC组、sh-LINC00894组、sh-LINC00894 + anti-NC组、sh-LINC00894 + anti-miR-205-5p组,用转染试剂将相应质粒转染至各组细胞中。qPCR法检测各组BGC823细胞和癌组织中LINC00894、miR-205-5p和GPNMB mRNA表达,双萤光素酶报告基因实验和AGO2-RNA免疫共沉淀验证LINC00894与miR-205-5P和miR-205-5p与GPNMB间的靶向结合关系。克隆形成实验、EdU染色、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、迁移和侵袭能力。WB法检测各组细胞中CDK1、MMP-2和MMP-9蛋白的表达。裸鼠移植瘤实验检测敲减LINC00894对移植瘤生长的影响,免疫组化法检测移植瘤组织中GPNMB蛋白的表达。结果:胃癌组织和细胞中LINC00894、GPNMB呈高表达,miR-205-5p呈低表达(均P < 0.05)。LINC00894与miR-205-5p和miR-205-5p与GPNMB之间存在靶向结合负向调控关系(均P < 0.05)。敲减LINC00894可促进BGC823细胞中miR-205-5p表达并抑制GPNMB表达(均P < 0.05),敲减LINC00894可抑制BGC823细胞的增殖、迁移和侵袭能力,以及抑制CDK1、MMP-2和MMP-9蛋白的表达(均P < 0.05),抑制miR-205-5p则可逆转此作用(均P < 0.05)。敲减LINC00894可抑制BGC823细胞移植瘤的生长、促进miR-205-5p表达、抑制GPNMB蛋白表达(均P < 0.05)。结论:在胃癌组织及细胞中LINC00894呈高表达,miR-205-5p呈低表达,敲减LINC00894表达可调控BGC823细胞中miR-205-5p/GPNMB通路蛋白表达并抑制其恶性生物学行为。

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