Autoimmune and inflammatory diseases are characterized by multifaceted pathogenesis, demanding effective therapeutic strategies.
Objectives
TNFSF10 is typically regarded as a pro-apoptotic ligand, yet its functions under physiological and pathological conditions remain elusive.
Methods
scRNA-seq analysis of immune cells from patients with aplastic anemia (AA) was performed to identify the crucial DEGs,with TNFSF10 being highlighted as a key regulator. Tnfsf10-deficient mice were used to establish an AA mouse model, and other mouse models, such as ER stress, aGVHD, radiation-induced aging, and IBD, which facilitated the exploration of the biological function of TNFSF10.
Results
Here, we show that TNFSF10 contributes to the imbalance of immune homeostasis and immunogenic cell death (ICD) under pathological circumstances. The ICD-provoking effect and proinflammatory property of TNFSF10 is associated with the activation of the NF-κB pathway and NLRP3 inflammasome. Additionally, TNFSF10 is a crucial amplifier of endoplasmic reticulum stress by enhancing the expression of PPP1R15A, thereby contributing to NLRP3 inflammasome activation. Moreover, TNFSF10-associated ER stress is a driver of surface Calreticulin (CALR) exposure, which transmits an “eat me” signal to hyperactivated immune cells and accelerates the clearance of hematopoietic cells. We also found that AA-specific exosomes may contribute to ER stress and the expression of TNFSF10.
Conclusion
Collectively, our study reveals the key role of TNFSF10 in autoimmune and inflammatory diseases, integrating the NF-κB, NLRP3 inflammasome, and ER stress pathways, and further accelerating the disease process.
{"title":"TNFSF10 drives hyperactive immune responses via NLRP3 inflammasome and endoplasmic reticulum stress in autoimmune and inflammatory diseases","authors":"Huilin Zhang, Yaoyao Chen, Yingmei Li, Chang Chen, Bingjie Wang, Fanxiang Yin, Yunling Zhu, Jiani Li, Jin Li, Ping Tang, Juanxia Zhou, Shaohua Yan, Bo Qin, Qingxuan Xin, Shuya Wang, Qiankun Yang, Baohong Yue, Yong Jiang, Rongqun Guo","doi":"10.1016/j.jare.2026.01.029","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.029","url":null,"abstract":"<h3>Introduction</h3>Autoimmune and inflammatory diseases are characterized by multifaceted pathogenesis, demanding effective therapeutic strategies.<h3>Objectives</h3>TNFSF10 is typically regarded as a pro-apoptotic ligand, yet its functions under physiological and pathological conditions remain elusive.<h3>Methods</h3>scRNA-seq analysis of immune cells from patients with aplastic anemia (AA) was performed to identify the crucial DEGs,with TNFSF10 being highlighted as a key regulator. Tnfsf10-deficient mice were used to establish an AA mouse model, and other mouse models, such as ER stress, aGVHD, radiation-induced aging, and IBD, which facilitated the exploration of the biological function of TNFSF10.<h3>Results</h3>Here, we show that TNFSF10 contributes to the imbalance of immune homeostasis and immunogenic cell death (ICD) under pathological circumstances. The ICD-provoking effect and proinflammatory property of TNFSF10 is associated with the activation of the NF-κB pathway and NLRP3 inflammasome. Additionally, TNFSF10 is a crucial amplifier of endoplasmic reticulum stress by enhancing the expression of PPP1R15A, thereby contributing to NLRP3 inflammasome activation. Moreover, TNFSF10-associated ER stress is a driver of surface Calreticulin (CALR) exposure, which transmits an “eat me” signal to hyperactivated immune cells and accelerates the clearance of hematopoietic cells. We also found that AA-specific exosomes may contribute to ER stress and the expression of TNFSF10.<h3>Conclusion</h3>Collectively, our study reveals the key role of TNFSF10 in autoimmune and inflammatory diseases, integrating the NF-κB, NLRP3 inflammasome, and ER stress pathways, and further accelerating the disease process.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"70 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-16DOI: 10.1016/j.jare.2026.01.034
Niklas Roeder, Antje Geiken, Vivian Schaarschmidt, Louisa Pannenbeckers, Stefan Dussling, Louise Holtmann, Julia Jensen-Kroll, Fynn Brix, Tim Hollstein, Tobias Demetrowitsch, Helen Gorges, Stanislav N. Gorb, Frank Will, Dominik M. Schulte, Mario Hasler, Ralf Schweiggert, Christof Dörfer, Karin Schwarz
Introduction
Excessive consumption of sugar-sweetened beverages is a major contributor to dental caries and a global public health concern due to its negative effects on oral health. Phenolic compounds found in edible plants have shown promising effects on caries prevention. Several studies indicate that these bioactive substances can inhibit caries formation through various mechanisms. However, studies which consider the complex interplay of the various factors are missing. In particular, human studies on the caries reducing effects of phenolic compounds in the co-presence of fermentable sugars are lacking.
Objective
This human intervention study investigated the effect of daily consumption of an apple juice-based drink enriched with phenolic compounds on caries development, compared to the exact same drink without phenolic compounds.
Methods
30 healthy male participants were enrolled in a double-blind, randomized, cross-over design. Caries development was measured using lesion depth in bovine tooth enamel samples installed in a removable dental appliance. A mixed model was used to analyze the data, including treatment effects, various oral parameters and interaction terms.
Results
The analysis showed that consumption of the drink enriched with phenolic compounds resulted in a significant reduction in enamel lesion depth compared to the control, after adjustment for oral parameters and their interactions.
Conclusion
Enrichment of phenolic compounds could be a promising strategy to mitigate the cariogenic effects of fermentable sugars in beverages. Analyzing the complex interactions between the oral parameters and treatment we bridge the translational gap of in vitro studies and achieve physiological relevance.
{"title":"Apple phenolic compounds enhance dental remineralization in human: a multifactorial in situ study","authors":"Niklas Roeder, Antje Geiken, Vivian Schaarschmidt, Louisa Pannenbeckers, Stefan Dussling, Louise Holtmann, Julia Jensen-Kroll, Fynn Brix, Tim Hollstein, Tobias Demetrowitsch, Helen Gorges, Stanislav N. Gorb, Frank Will, Dominik M. Schulte, Mario Hasler, Ralf Schweiggert, Christof Dörfer, Karin Schwarz","doi":"10.1016/j.jare.2026.01.034","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.034","url":null,"abstract":"<h3>Introduction</h3>Excessive consumption of sugar-sweetened beverages is a major contributor to dental caries and a global public health concern due to its negative effects on oral health. Phenolic compounds found in edible plants have shown promising effects on caries prevention. Several studies indicate that these bioactive substances can inhibit caries formation through various mechanisms. However, studies which consider the complex interplay of the various factors are missing. In particular, human studies on the caries reducing effects of phenolic compounds in the co-presence of fermentable sugars are lacking.<h3>Objective</h3>This human intervention study investigated the effect of daily consumption of an apple juice-based drink enriched with phenolic compounds on caries development, compared to the exact same drink without phenolic compounds.<h3>Methods</h3>30 healthy male participants were enrolled in a double-blind, randomized, cross-over design. Caries development was measured using lesion depth in bovine tooth enamel samples installed in a removable dental appliance. A mixed model was used to analyze the data, including treatment effects, various oral parameters and interaction terms.<h3>Results</h3>The analysis showed that consumption of the drink enriched with phenolic compounds resulted in a significant reduction in enamel lesion depth compared to the control, after adjustment for oral parameters and their interactions.<h3>Conclusion</h3>Enrichment of phenolic compounds could be a promising strategy to mitigate the cariogenic effects of fermentable sugars in beverages. Analyzing the complex interactions between the oral parameters and treatment we bridge the translational gap of <em>in vitro</em> studies and achieve physiological relevance.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"19 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.jare.2026.01.020
Parvaiz Ahmad Naik, Bijal M. Yeolekar, Kolade M. Owolabi, Mahesh Yeolekar
{"title":"Modeling and analyzing glucose-insulin interactions during diabetes through fractional dynamics in presence of glucagon","authors":"Parvaiz Ahmad Naik, Bijal M. Yeolekar, Kolade M. Owolabi, Mahesh Yeolekar","doi":"10.1016/j.jare.2026.01.020","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.020","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"55 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-13DOI: 10.1016/j.jare.2026.01.031
Yuchuan Li, Hong Zhang, Mingle Wang, Fei Guo, Pu Wang, Xia Wang, Yuqiong Chen, Xiaoting Zhai, Xiaochun Wan, Dejiang Ni
{"title":"Study on the formation mechanism of the key fresh aroma component (Z)-3-hexen-1-ol during the spreading process of lu’an Guapian green tea","authors":"Yuchuan Li, Hong Zhang, Mingle Wang, Fei Guo, Pu Wang, Xia Wang, Yuqiong Chen, Xiaoting Zhai, Xiaochun Wan, Dejiang Ni","doi":"10.1016/j.jare.2026.01.031","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.031","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"84 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/j.jare.2026.01.032
Bin Qian, Shuya Mao, Yang Chen, Ying Liu, Mingchao Zhang, Dihan Zhu, Ke Zen, Yu Wang, Zhihong Liu, Limin Li
Minimal Change Disease (MCD) represents a prevalent pathological cause of nephrotic syndrome. While podocyte injury is recognized as the direct cause of proteinuria in MCD, aberrant T-cell activation is a key driver of this podocyte damage. However, the absence of T-cell infiltration in renal biopsies and ineffectiveness of immunosuppressive therapy in a subset of patients suggest the existence of undiscovered key mechanisms underlying MCD immunopathogenesis.
{"title":"Podocyte-derived exosomes instruct dendritic cell-dependent CD8+ T cell activation and proliferation in renal inflammation","authors":"Bin Qian, Shuya Mao, Yang Chen, Ying Liu, Mingchao Zhang, Dihan Zhu, Ke Zen, Yu Wang, Zhihong Liu, Limin Li","doi":"10.1016/j.jare.2026.01.032","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.032","url":null,"abstract":"Minimal Change Disease (MCD) represents a prevalent pathological cause of nephrotic syndrome. While podocyte injury is recognized as the direct cause of proteinuria in MCD, aberrant T-cell activation is a key driver of this podocyte damage. However, the absence of T-cell infiltration in renal biopsies and ineffectiveness of immunosuppressive therapy in a subset of patients suggest the existence of undiscovered key mechanisms underlying MCD immunopathogenesis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"15 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ferroptosis significantly compromises diabetic wound healing and represents a promising therapeutic target for clinical intervention. Baicalein (Bai), a natural flavonoid, has been considered to own ferroptosis-regulating properties, while the underlying mechanisms remain understood.
Pseudomonas syringae pv. tabaci, a Gram-negative bacterial pathogen, causes devastating tobacco wildfire disease with global economic impacts. While its pathogenicity is well documented, the dynamic defense mechanisms of tobacco against infection remain poorly understood.
{"title":"Time-series transcriptome and metabolome profiling Uncovers WRKY6 and WRKY23 as critical regulators in tobacco response to Pseudomonas syringae infection","authors":"Xinhua Tian, Peng Lu, Zechao Qu, Huan Su, Qiao Wang, Jiemeng Tao, Qian Sun, Shuaibin Wang, Lijun Meng, Peijian Cao, Yuanhu Xuan, Jingjing Jin","doi":"10.1016/j.jare.2026.01.036","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.036","url":null,"abstract":"<ce:italic>Pseudomonas syringae</ce:italic> pv. <ce:italic>tabaci</ce:italic>, a Gram-negative bacterial pathogen, causes devastating tobacco wildfire disease with global economic impacts. While its pathogenicity is well documented, the dynamic defense mechanisms of tobacco against infection remain poorly understood.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"11 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：