Journal of Advanced Research最新文献

{"title":"Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice","authors":"Shengjie Li ,&nbsp;Aoxiang Zhuge ,&nbsp;Hui Chen ,&nbsp;Shengyi Han ,&nbsp;Jian Shen ,&nbsp;Kaicen Wang ,&nbsp;Jiafeng Xia ,&nbsp;He Xia ,&nbsp;Shiman Jiang ,&nbsp;Youhe Wu ,&nbsp;Lanjuan Li","doi":"10.1016/j.jare.2024.03.026","DOIUrl":"10.1016/j.jare.2024.03.026","url":null,"abstract":"<div><h3>Introduction</h3><div>Inflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that sedanolide exerts anti-oxidative and anti-inflammatory effects as a natural phthalide, but its effects on IBD remain unclear.</div></div><div><h3>Objectives</h3><div>In this study, we investigated the impacts of sedanolide on dextran sodium sulfate (DSS)-induced colitis in mice.</div></div><div><h3>Methods</h3><div>The mice were administered sedanolide or vehicle followed by DSS administration, after which colitis symptoms, inflammation levels, and intestinal barrier function were evaluated. Transcriptome analysis, 16S rRNA sequencing, and targeted metabolomics analysis of bile acids and lipids were performed.</div></div><div><h3>Results</h3><div>Sedanolide protected mice from DSS-induced colitis, suppressed the inflammation, restored the weakened epithelial barrier, and modified the gut microbiota by decreasing bile salt hydrolase (BSH)-expressing bacteria. The downregulation of BSH activity by sedanolide increased the ratio of conjugated/unconjugated bile acids (BAs), thereby inhibiting the intestinal farnesoid X receptor (FXR) pathway. The roles of the FXR pathway and gut microbiota were verified using an intestinal FXR-specific agonist (fexaramine) and germ-free mice, respectively. Furthermore, we identified the key effector ceramide, which is regulated by sphingomyelin phosphodiesterase 3 (SMPD3). The protective effects of ceramide (d18:1/16:0) against inflammation and the gut barrier were demonstrated in vitro using the human cell line Caco-2.</div></div><div><h3>Conclusion</h3><div>Sedanolide could reshape the intestinal flora and influence BA composition, thus inhibiting the FXR-SMPD3 pathway to stimulate the synthesis of ceramide, which ultimately alleviated DSS-induced colitis in mice. Overall, our research revealed the protective effects of sedanolide against DSS-induced colitis in mice, which indicated that sedanolide may be a clinical treatment for colitis. Additionally, the key lipid ceramide (d18:1/16:0) was shown to mediate the protective effects of sedanolide, providing new insight into the associations between colitis and lipid metabolites.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 413-426"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of human astrocytes with potent therapeutic functions from human pluripotent stem cells using ventral midbrain patterning","authors":"Ye Rim Nam ,&nbsp;Minji Kang ,&nbsp;Minji Kim ,&nbsp;Min Jong Seok ,&nbsp;Yunseon Yang ,&nbsp;Young Eun Han ,&nbsp;Soo-Jin Oh ,&nbsp;Do Gyeong Kim ,&nbsp;Hyeon Son ,&nbsp;Mi-Yoon Chang ,&nbsp;Sang-Hun Lee","doi":"10.1016/j.jare.2024.03.012","DOIUrl":"10.1016/j.jare.2024.03.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Astrocytes are glial-type cells that protect neurons from toxic insults and support neuronal functions and metabolism in a healthy brain. Leveraging these physiological functions, transplantation of astrocytes or their derivatives has emerged as a potential therapeutic approach for neurodegenerative disorders.</div></div><div><h3>Methods</h3><div>To substantiate the clinical application of astrocyte-based therapy, we aimed to prepare human astrocytes with potent therapeutic capacities from human pluripotent stem cells (hPSCs). To that end, we used ventral midbrain patterning during the differentiation of hPSCs into astrocytes, based on the roles of midbrain-specific factors in potentiating glial neurotrophic/anti-inflammatory activity. To assess the therapeutic effects of human midbrain-type astrocytes, we transplanted them into mouse models of Parkinson's disease (PD) and Alzheimer's disease (AD).</div></div><div><h3>Results</h3><div>Through a comprehensive series of <em>in-vitro</em> and <em>in-vivo</em> experiments, we were able to establish that the midbrain-type astrocytes exhibited the abilities to effectively combat oxidative stress, counter excitotoxic glutamate, and manage pathological protein aggregates. Our strategy for preparing midbrain-type astrocytes yielded promising results, demonstrating the strong therapeutic potential of these cells in various neurotoxic contexts. Particularly noteworthy is their efficacy in PD and AD-specific proteopathic conditions, in which the midbrain-type astrocytes outperformed forebrain-type astrocytes derived by the same organoid-based method.</div></div><div><h3>Conclusion</h3><div>The enhanced functions of the midbrain-type astrocytes extended to their ability to release signaling molecules that inhibited neuronal deterioration and senescence while steering microglial cells away from a pro-inflammatory state. This success was evident in both <em>in-vitro</em> studies using human cells and <em>in-vivo</em> experiments conducted in mouse models of PD and AD. In the end, our human midbrain-type astrocytes demonstrated remarkable effectiveness in alleviating neurodegeneration, neuroinflammation, and the pathologies associated with the accumulation of α-synuclein and Amyloid β proteins.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 181-196"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kurarinone regulates Th17/Treg balance and ameliorates autoimmune uveitis via Rac1 inhibition","authors":"Chenyang Gu ,&nbsp;Yidan Liu ,&nbsp;Jianjie Lv ,&nbsp;Chun Zhang ,&nbsp;Zhaohao Huang ,&nbsp;Qi Jiang ,&nbsp;Yuehan Gao ,&nbsp;Tianyu Tao ,&nbsp;Yuhan Su ,&nbsp;Binyao Chen ,&nbsp;Renbing Jia ,&nbsp;Xiuxing Liu ,&nbsp;Wenru Su","doi":"10.1016/j.jare.2024.03.013","DOIUrl":"10.1016/j.jare.2024.03.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Autoimmune uveitis (AU) is a severe intraocular autoimmune disorder with a chronic disease course and a high rate of blindness. Kurarinone (KU), a major component of the traditional Chinese medicine Sophorae Flavescentis Radix, possesses a wide spectrum of activities and has been used to treat several inflammation-related diseases.</div></div><div><h3>Objective</h3><div>We aimed to investigate the effects of KU on AU and its modulatory mechanisms.</div></div><div><h3>Methods</h3><div>We used an experimental autoimmune uveitis (EAU) animal model and characterized the comprehensive immune landscape of KU-treated EAU mice using single-cell RNA sequencing (scRNA-seq). The retina and lymph nodes were analyzed. The siRNAs and selective inhibitors were used to study the signaling pathway. The effect of KU on peripheral blood mononuclear cells (PBMCs) from uveitis patients was also examined.</div></div><div><h3>Results</h3><div>We found that KU relieved chorioretinal lesions and immune cell infiltration in EAU model mice. Subsequent single-cell analysis revealed that KU downregulated the EAU-upregulated expression of inflammatory and autoimmune-related genes and suppressed pathways associated with immune cell differentiation, activation, and migration in a cell-specific manner. KU was implicated in restoring T helper 17 (Th17)/regulatory T (Treg) cell balance by alleviating inflammatory injury and elevating the expression of modulatory mediators in Tregs, while simultaneously ameliorating excessive inflammation by Th17 cells. Furthermore, Rac1 and the Id2/Pim1 axis potentiated the pathogenicity of Th17 cells during EAU, which was inhibited by KU treatment, contributing to the amelioration of EAU-induced inflammation and treatment of AU. In addition, KU suppressed inflammatory cytokine production in activated human PBMCs by inhibiting Rac1. Integration of the glucocorticoid-treated transcriptome suggests that KU has immunomodulatory effects on lymphocytes.</div></div><div><h3>Conclusion</h3><div>Our study constructed a high-resolution atlas of the immunoregulatory effects of KU treatment on EAU and identified its potential therapeutic mechanisms, which hold great promise in treating autoimmune disorders.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 381-398"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding multicomponent low molecular weight gels from gelators to networks","authors":"Liangchun Li ,&nbsp;Renlin Zheng ,&nbsp;Rongqin Sun","doi":"10.1016/j.jare.2024.03.028","DOIUrl":"10.1016/j.jare.2024.03.028","url":null,"abstract":"<div><h3>Background</h3><div>The construction of gels from low molecular weight gelators (LMWG) has been extensively studied in the fields of bio-nanotechnology and other fields. However, the understanding gaps still prevent the prediction of LMWG from the full design of those gel systems. Gels with multicomponent become even more complicated because of the multiple interference effects coexist in the composite gel systems.</div></div><div><h3>Aim of review</h3><div>This review emphasizes systems view on the understanding of multicomponent low molecular weight gels (MLMWGs), and summarizes recent progress on the construction of desired networks of MLMWGs, including self-sorting and co-assembly, as well as the challenges and approaches to understanding MLMWGs, with the hope that the opportunities from natural products and peptides can speed up the understanding process and close the gaps between the design and prediction of structures.</div></div><div><h3>Key scientific concepts of review</h3><div>This review is focused on three key concepts. Firstly, understanding the complicated multicomponent gels systems requires a systems perspective on MLMWGs. Secondly, several protocols can be applied to control self-sorting and co-assembly behaviors in those multicomponent gels system, including the certain complementary structures, chirality inducing and dynamic control. Thirdly, the discussion is anchored in challenges and strategies of understanding MLMWGs, and some examples are provided for the understanding of multicomponent gels constructed from small natural products and subtle designed short peptides.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 91-106"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-Induced Reduction of IGF1R Sumoylation Attenuates Neuroinflammation in APP/PS1 Transgenic Mice","authors":"Yisheng Chen ,&nbsp;Xiaofeng Chen ,&nbsp;Zhiwen Luo ,&nbsp;Xueran Kang ,&nbsp;Yunshen Ge ,&nbsp;Renwen Wan ,&nbsp;Qian Wang ,&nbsp;Zhihua Han ,&nbsp;Fangqi Li ,&nbsp;Zhongcheng Fan ,&nbsp;Yuchun Xie ,&nbsp;Beijie Qi ,&nbsp;Xintao Zhang ,&nbsp;Zhenwei Yang ,&nbsp;John H Zhang ,&nbsp;Danping Liu ,&nbsp;Yuzhen Xu ,&nbsp;Dongyan Wu ,&nbsp;Shiyi Chen","doi":"10.1016/j.jare.2024.03.025","DOIUrl":"10.1016/j.jare.2024.03.025","url":null,"abstract":"<div><h3>Introduction</h3><div>Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R) and its post-translational modifications, especially sumoylation, is crucial in understanding the progression of AD and exploring novel therapeutic avenues.</div></div><div><h3>Objectives</h3><div>This study investigates the impact of exercise on the sumoylation of IGF1R and its role in ameliorating AD symptoms in APP/PS1 mice, with a specific focus on neuroinflammation and innovative therapeutic strategies.</div></div><div><h3>Methods</h3><div>APP/PS1 mice were subjected to a regimen of moderate-intensity exercise. The investigation encompassed assessments of cognitive functions, alterations in hippocampal protein expressions, neuroinflammatory markers, and the effects of exercise on IGF1R and SUMO1 nuclear translocation. Additionally, the study evaluated the efficacy of KPT-330, a nuclear export inhibitor, as an alternative to exercise.</div></div><div><h3>Results</h3><div>Exercise notably enhanced cognitive functions in AD mice, possibly through modulations in hippocampal proteins, including Bcl-2 and BACE1. A decrease in neuroinflammatory markers such as IL-1β, IL-6, and TNF-α was observed, indicative of reduced neuroinflammation. Exercise modulated the nuclear translocation of SUMO1 and IGF1R in the hippocampus, thereby facilitating neuronal regeneration. Mutant IGF1R (MT IGF1R), lacking SUMO1 modification sites, showed reduced SUMOylation, leading to diminished expression of pro-inflammatory cytokines and apoptosis. KPT-330 impeded the formation of the IGF1R/RanBP2/SUMO1 complex, thereby limiting IGF1R nuclear translocation, inflammation, and neuronal apoptosis, while enhancing cognitive functions and neuron proliferation.</div></div><div><h3>Conclusion</h3><div>Moderate-intensity exercise effectively mitigates AD symptoms in mice, primarily by diminishing neuroinflammation, through the reduction of IGF1R Sumoylation. KPT-330, as a potential alternative to physical exercise, enhances the neuroprotective role of IGF1R by inhibiting SUMOylation through targeting XPO1, presenting a promising therapeutic strategy for AD.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 279-297"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140399653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginger exosome-like nanoparticle-derived miRNA therapeutics: A strategic inhibitor of intestinal inflammation","authors":"Ling Yan ,&nbsp;Yaqi Cao ,&nbsp;Linhai Hou ,&nbsp;Tianyu Luo ,&nbsp;Meiqi Li ,&nbsp;Shengjie Gao ,&nbsp;Lei Wang ,&nbsp;Kangliang Sheng ,&nbsp;Lei Zheng","doi":"10.1016/j.jare.2024.04.001","DOIUrl":"10.1016/j.jare.2024.04.001","url":null,"abstract":"<div><h3>Introduction</h3><div>MicroRNAs (miRNAs) involve in destabilising messenger RNA or repressing translation of target molecules. Ginger-derived exosome-like nanoparticles (GELNs) play a crucial role in modulating intestinal inflammation. Moreover, GELNs contain highly heterogeneous miRNA. However, the role of miRNAs derived from GELNs in immunomodulation remains unclear.</div></div><div><h3>Objectives</h3><div>This study aimed to elucidate the molecular basis of the unique biological effects mediated by miRNA derived from GELNs on macrophages.</div></div><div><h3>Methods</h3><div>GELNs were isolated using a combination of commercial exosome isolation kits and the differential centrifugation method, and the lipid composition of GELNs was determined using liquid chromatography-mass spectrometry. Subsequently, PKH26 labelled GELNs were taken up by macrophages. Furthermore, the modulation of inflammatory and immune responses by GELNs or osa-miR164d was assessed through the RNA-seq, RT-qPCR, online databases, and dual luciferase reporter assays to explore the underlying mechanisms of osa-miR164d. Biomimetic exosomes loaded with osa-miR164d were prepared using a microfluidic mixing device and systematically characterized. The therapeutic effects of osa-miR164d on relieving colitis were evaluated.</div></div><div><h3>Results</h3><div>We report for the first time that GELNs-derived osa-miR164d is a regulatory factor of reprogramming macrophage polarization, thereby inhibiting the intestinal inflammatory response. Mechanistically, osa-miR164d directly targets the 3′-UTRs of TAB1, which regulates macrophage polarization through the downregulation of NF-κB expression. In addition, We have designed a biomimetic exosome mimicking GELNs to deliver osa-miR164d (osa-miR164d-MGELNs). Notably, the osa-miR164d-MGELNs can efficiently reprogram macrophages to alleviate colitis-related symptoms.</div></div><div><h3>Conclusion</h3><div>Our findings enhance the systematic understanding of how GELNs-derived osa-miR164d mediates cross-kingdom communication and provide an original engineering paradigm for mimicking GELNs to transfer miRNA.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 1-15"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating β-Catenin nuclear translocation","authors":"Bin Liu ,&nbsp;Ihtisham Bukhari ,&nbsp;Fazhan Li ,&nbsp;Feifei Ren ,&nbsp;Xue Xia ,&nbsp;Baitong Hu ,&nbsp;Haipeng Liu ,&nbsp;Thomas F Meyer ,&nbsp;Barry J. Marshall ,&nbsp;Alfred Tay ,&nbsp;Yuming Fu ,&nbsp;Wanqing Wu ,&nbsp;Youcai Tang ,&nbsp;Yang Mi ,&nbsp;Peng-Yuan Zheng","doi":"10.1016/j.jare.2024.04.002","DOIUrl":"10.1016/j.jare.2024.04.002","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Helicobacter pylori (H. pylori)</em> infection has been associated with gastric carcinogenesis. However, the precise involvement of LRP8, the low-density lipoprotein receptor-related protein 8, in <em>H. pylori</em> pathogenesis and gastric cancer (GC) remains poorly understood.</div></div><div><h3>Objectives</h3><div>To investigate the potential role of LRP8 in <em>H. pylori</em> infection and gastric carcinogenesis.</div></div><div><h3>Methods</h3><div>Three-dimensional human-derived gastric organoids (hGO) and gastric cancer organoids (hGCO) were synthesized from the tissues obtained from human donors. In this work, multi-omics combined with <em>in vivo and in vitro</em> studies were conducted to investigate the potential involvement of LRP8 in <em>H. pylori-</em>induced GC.</div></div><div><h3>Results</h3><div>We found that <em>H. pylori</em> infection significantly upregulated the expression of LRP8 in human GC tissues, cells, organoids, and mouse gastric mucous. In particular, LRP8 exhibited a distinct enrichment in cancer stem cells (CSC). Functionally, silencing of LRP8 affected the formation and proliferation of tumor spheroids, while increased expression of LRP8 was associated with increased proliferation and stemness of GC cells and organoids. Mechanistically, LRP8 promotes the binding of E-cadherin to β-catenin, thereby promoting nuclear translocation and transcriptional activity of β-catenin. Furthermore, LRP8 interacts with the cytotoxin-associated gene A (CagA) to form the CagA/LRP8/β-catenin complex. This complex further amplifies <em>H. pylori</em>-induced β-catenin nuclear translocation, leading to increased transcription of inflammatory factors and CSC markers. Clinical analysis demonstrated that abnormal overexpression of LRP8 is correlated with a poor prognosis and resistance to 5-Fluorouracil in patients with GC.</div></div><div><h3>Conclusion</h3><div>Our findings provide valuable information on the molecular intricacies of <em>H. pylori</em>-induced gastric carcinogenesis, offering potential therapeutic targets and prognostic markers for GC.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 299-312"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140772557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease","authors":"Won-Kyu Rhim ,&nbsp;Jiwon Woo ,&nbsp;Jun Yong Kim ,&nbsp;Eun Hye Lee ,&nbsp;Seung-Gyu Cha ,&nbsp;Da-Seul Kim ,&nbsp;Seung-Woon Baek ,&nbsp;Chun Gwon Park ,&nbsp;Bum Soo Kim ,&nbsp;Tae Gyun Kwon ,&nbsp;Dong Keun Han","doi":"10.1016/j.jare.2024.03.018","DOIUrl":"10.1016/j.jare.2024.03.018","url":null,"abstract":"<div><h3>Introduction</h3><div>With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function <em>via</em> tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging.</div></div><div><h3>Objectives</h3><div>To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds.</div></div><div><h3>Methods</h3><div>Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)₂ (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold.</div></div><div><h3>Results</h3><div>With functionalities of Mg(OH)₂ and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD.</div></div><div><h3>Conclusion</h3><div>Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 75-89"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding and reconstructing disease relations between dry eye and depression: a multimodal investigation comprising meta-analysis, genetic pathways and Mendelian randomization","authors":"Kao-Jung Chang ,&nbsp;Hsin-Yu Wu ,&nbsp;Pin-Hsuan Chiang ,&nbsp;Yu-Tien Hsu ,&nbsp;Pei-Yu Weng ,&nbsp;Ting-Han Yu ,&nbsp;Cheng-Yi Li ,&nbsp;Yu-Hsiang Chen ,&nbsp;He-Jhen Dai ,&nbsp;Han-Ying Tsai ,&nbsp;Yu-Jung Chang ,&nbsp;You-Ren Wu ,&nbsp;Yi-Ping Yang ,&nbsp;Cheng-Ta Li ,&nbsp;Chih-Chien Hsu ,&nbsp;Shih-Jen Chen ,&nbsp;Yu-Chun Chen ,&nbsp;Ching-Yu Cheng ,&nbsp;Ai-Ru Hsieh ,&nbsp;Shih-Hwa Chiou","doi":"10.1016/j.jare.2024.03.015","DOIUrl":"10.1016/j.jare.2024.03.015","url":null,"abstract":"<div><h3>Introduction</h3><div>The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined.</div></div><div><h3>Objectives</h3><div>To this end, we set up a three-segment study that employed multimodality results (<em>meta</em>-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP.</div></div><div><h3>Methods</h3><div>A <em>meta</em>-analysis comprising 26 case−control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP.</div></div><div><h3>Results</h3><div>Our <em>meta</em>-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (r_G = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein−protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (<em>p</em> value &lt;0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained.</div></div><div><h3>Conclusion</h3><div>With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 197-213"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-frequency magnetic field therapy for glioblastoma: Current advances, mechanisms, challenges and future perspectives","authors":"Yinlong Liu ,&nbsp;Qisheng Tang ,&nbsp;Quan Tao ,&nbsp;Hui Dong ,&nbsp;Zhifeng Shi ,&nbsp;Liangfu Zhou","doi":"10.1016/j.jare.2024.03.024","DOIUrl":"10.1016/j.jare.2024.03.024","url":null,"abstract":"<div><h3>Background</h3><div>Glioblastoma (GBM) is the most common malignant tumour of the central nervous system. Despite recent advances in multimodal GBM therapy incorporating surgery, radiotherapy, systemic therapy (chemotherapy, targeted therapy), and supportive care, the overall survival (OS) remains poor, and long-term survival is rare. Currently, the primary obstacles hindering the effectiveness of GBM treatment are still the blood-brain barrier and tumor heterogeneity. In light of its substantial advantages over conventional therapies, such as strong penetrative ability and minimal side effects, low-frequency magnetic fields (LF-MFs) therapy has gradually caught the attention of scientists.</div></div><div><h3>Aim of Review</h3><div>In this review, we shed the light on the current status of applying LF-MFs in the treatment of GBM. We specifically emphasize our current understanding of the mechanisms by which LF-MFs mediate anticancer effects and the challenges faced by LF-MFs in treating GBM cells. Furthermore, we discuss the prospective applications of magnetic field therapy in the future treatment of GBM.</div><div><em>Key scientific concepts of review:</em> The review explores the current progress on the use of LF-MFs in the treatment of GBM with a special focus on the potential underlying mechanisms of LF-MFs in anticancer effects. Additionally, we also discussed the complex magnetic field features and biological characteristics related to magnetic bioeffects. Finally, we proposed a promising magnetic field treatment strategy for future applications in GBM therapy.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"69 ","pages":"Pages 531-543"},"PeriodicalIF":11.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}