Vol. 30 (2025)
| No. 01 | DOI: 10.1186/s11658-025-00827-2 Volume 31 (2026) - 30:01 | |
| Title | LOSS OF ALPHA-KINASE 1 CONTRIBUTES TO THE FORMATION OF CONGENITAL CATARACTS IN MICE | |
| Authors | Hui-Shan Wang1†, Yu-Xin Yang1†, Shang-Shang Duan1†, Fang-Yi Long2, Ting Wu1, Nai-Hong Yan1, Xiao-Hong Li1* and Jun-Rong Du1* | |
| Abstract | Background:
Alpha-kinase 1 (ALPK1), a cytosolic receptor involved in innate immune activation, promotes apical trafficking in epithelial cells. While its role in autoinflammatory disorders is known, its function in epithelial homeostasis remains unexplored. This study investigates ALPK1’s role in murine lens development and its pathological relevance to congenital cataracts (CCs). Methods: We utilized ALPK1-deficient (ALPK1−/−) C57BL/6 mice and primary lens epithelial cells (LECs) with ALPK1 knockout (via lentiviral sgRNA) to analyze lens histo-morphological alterations and cellular and molecular pathologies, including apical protein transport and localization, endoplasmic reticulum (ER) stress, apoptosis, and LEC differentiation. Results: We observed strong ALPK1 immunoreactivity in the LECs of C57BL/6 mice. ALPK1−/− mice developed CCs with combined Y-suture and cortical opacities, disrupted lens cell architecture, and vacuolar degeneration. Molecular dysregulation included reduced phosphorylation of myosin Ia, mislocalization of zonula occludens-1 (ZO-1) from apical tight junctions to cytoplasmic aggregates, upregulation of the endoplasmic reticulum (ER) stress marker C/EBP-homologous protein (CHOP), increased apoptosis (evidenced by TUNEL-positive cells), and disorganized interlocking patterns in lens fiber cells. Lentiviral ALPK1 re-expression in ALPK1−/− mice significantly restored lens transparency and ZO-1 apical localization, reduced CHOP expression, and suppressed apoptosis. Conclusions: This study first demonstrates that ALPK1 is critical for maintaining LEC homeostasis by regulating myosin Ia phosphorylation-dependent apical trafficking and tight junction integrity. ALPK1 deficiency disrupts these processes, leading to loss of apical polarity, ER stress-induced apoptosis, and ultimately CC formation. | |
| Keywords | ALPK1, Apical transport, Congenital cataracts, Lens epithelial cells, Myosin Ia | |
| Address and Contact Information |
1 West China School of Pharmacy, West China School of Public Health, Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China 2 Laboratory Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu 610032, Sichuan, China *Corresponding author: Xiao-Hong Li li_xiaohong@scu.edu.cn Jun-Rong Du dujunrong@scu.edu.cn † Hui-Shan Wang, Yu-Xin Yang and Shang-Shang Duan have contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 03 | DOI: 10.1186/s11658-025-00831-6 Volume 31 (2026) - 30:03 | |
| Title | TRIGEMINAL NERVE ROOT COMPRESSION INDUCED NEUROINFLAMMATORY RESPONSE PROMOTES MECHANICAL ALLODYNIA THROUGH THE CGRP/SP-Piezo2 AXIS VIA Ca2+ SIGNALING | |
| Authors | Xinyue Liao1†, Zhaoke Luo1†, Feng Huang1†, Yiqian Wang1, Zhangying Zeng1, Weihang Liao1, Yating Ou1, Xuemei Wu1, Feng Wang1,2* and Daoshu Luo1,2* | |
| Abstract | Trigeminal neuralgia (TN) is one of the most severe types of neuropathic pain, but its pathological mechanisms remain unknown. In this study, we identified a unique neuroinflammatory response induced by chronic compression of trigeminal root entry zone (TREZ) in a TN rat model, establishing a connection between ATP-driven intracellular pathways and Piezo2-mediated mechanotransduction. Piezo2, the pain-related neuropeptide calcitonin gene-related peptide (CGRP) receptor complex CRLR-RAMP1 and the neuropeptide substance-P (SP) receptor NK1R are co-expressed on rat Merkel cells. Protein kinase C (PKC) plays a crucial role in upregulating Piezo2 and CGRP/SP expression in both the trigeminal ganglion (TG) and whisker pad, thereby facilitating orofacial mechanical allodynia in TN rats. Furthermore, the inhibition of cAMP signaling in the whisker pads effectively alleviated mechanical allodynia, while Piezo2 knockdown in both the TG and whisker pads significantly reversed db cAMP-induced allodynia. In vitro studies demonstrated that extracellular ATP not only enhances CGRP and SP expression but also induces Piezo2 expression through Ca2+-dependent activation of ERK1/2 and p38 MAPK cascades, mediated by specific transcription factors. These findings reveal that peripheral sensitization in TN is mediated through a Ca2+-CGRP/SP-Piezo2 positive feedback loop, dependent on the neuroinflammatory response along the TG neuron–Merkel cell axis as a prerequisite condition. This discovery provides a novel insight into the pathogenesis of TN. | |
| Keywords | Piezo2, CGRP/SP, Neuroinflammation, Trigeminal neuralgia, Ca2+-PKC | |
| Address and Contact Information | 1 Laboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Key Laboratory of Brain Aging and Neurodegenerative Diseases of Fujian Province, Fujian Medical University, 350122 Fuzhou, China 2 Department of Human Anatomy, The School of Basic Medical Sciences, Fujian Medical University, No. 1 Xuefu North Road, University Town 350122, Fuzhou, China *Corresponding author: Feng Wang fjwf95168@163.com Daoshu Luo luods2004@fjmu.edu.cn † Xinyue Liao, Zhaoke Luo and Feng Huang contributed equally to this work. | |
| Read full article at BMC | ||
| No. 04 | DOI: 10.1186/s11658-025-00816-5 Volume 31 (2026) - 30:04 | |
| Title | tsRNA-3040b ACCUMULATES R-LOOP TO REGULATe Trim35 TRANSCRIPTION, WHICH LEADS TO DISORDERED GLYCOLYSIS AND PROMOTES PAECS PROLIFERATION | |
| Authors | Xu Wang1†, Songyue Li1†, Jianli Hou1, Shukun Cao2, Yibin Zhang1, Jingya Zhang1, Xinru Wang1, Xinyue Song3, Ya Xu3, Jing Qi1, Yan Xing1,4* and Xiaodong Zheng2,4* | |
| Abstract | Background:
Hypoxia significantly influences the development of pulmonary hypertension (PH). However, the role of transfer RNA-derived small RNAs (tsRNAs) produced by nuclease cleavage on PH, particularly their impact on the proliferation of pulmonary artery endothelial cells (PAECs), remains unclear. Methods: To detect tsRNA expression, panoramic RNA display by overcoming RNA modification aborted sequencing (PANDORA-seq) sequencing analysis and quantitative polymerase chain reaction (qPCR) were employed. The formation of R-loops between tsRNA and genomic DNA was confirmed through chromatin immunoprecipitation followed by polymerase chain reaction (ChIP-PCR) and Dot-blot analyses. Mouse PAECs and lung tissue were manipulated to either overexpress or inhibit tsRNA-3040b, followed by assessments of cell proliferation, RT-qPCR, and enzyme activity assays on three key glycolytic rate-limiting enzymes. Molecular docking, immunofluorescence and endogenous coprecipitation were used to demonstrate the colocalization of Trim35 and Wnt3a. Results: The expression of tsRNA-Asp-GTC-3040b (termed tsRNA-3040b) was significantly increased in the lung tissue of a hypoxia-induced PH mouse model. By integrating database prediction with RNA sequencing, Trim35 was identified as a downstream target of tsRNA-3040b. ChIP-PCR and Dot-blot analyses using S9.6 indicated that tsRNA-3040b promoted R-loops in the genomic DNA of Trim35, thus inhibiting its transcription. Further investigation revealed that the Trim35 affected glucose metabolism levels through ubiquitinated substrate Wnt3a. Ultimately, it was elucidated that the tsRNA-3040b–Trim35–Wnt3a–glucose metabolism signaling pathway exacerbated the progression of PH. Conclusions: This study highlights the role of tsRNA-3040b in promoting PH by influencing glucose metabolism processes. These results offer a new approach to treating PH and suggest that tsRNA-3040b could serve as a potential target for diagnosing PH and related conditions. | |
| Keywords | Pulmonary hypertension, Glucose metabolism reprogramming, tRNA-derived small RNAs, R-loops, Trim35, Wnt3A, Cell proliferation | |
| Address and Contact Information |
1 Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, Heilongjiang, People’s Republic of China 2 Department of Medical Genetics, Harbin Medical University-Daqing, Daqing 163319, Heilongjiang, People’s Republic of China 3 Central Laboratory, Harbin Medical University-Daqing, Daqing 163319, Heilongjiang, People’s Republic of China 4 Engineering Technology Research Center for Precision Diagnosis and Treatment of Frigid Zone-Related Diseases in Heilongjiang Province, Daqing, Heilongjiang 163319, People’s Republic of China *Corresponding author: Yan Xing xingyan@hmudq.edu.cn Xiaodong Zheng zhengxiaodong@hmudq.edu.cn † Xu Wang and Songyue Li contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 06 | DOI: 10.1186/s11658-025-00835-2 Volume 31 (2026) - 30:06 | |
| Title | A NOVEL tRF-Gly IS ASSOCIATED WITH OBESITY DEVELOPMENT THROUGH POST-TRANSCRIPTIONAL REGULATION OF LIPID METABOLISM | |
| Authors | Yuhang Lei1,2,3†, Mailin Gan1,2,3†, Kai Wang1,2,3†, Tianci Liao1,2,3, Yiting Yang1,2,3, Xue Zhao1,2,4, Xin Zhang1,2,3, Dujun Chen1,2,3, Xinyi Wang1,2,3, Jianfeng Ma1,2,3, Lili Niu1,2,3, Ye Zhao1,2,3, Lei Chen1,2,3, Xiaofeng Zhou1,2,3, Yan Wang1,2,3, Mingzhou Li1,2,3, Li Zhu1,2,3* and Linyuan Shen1,2,3* | |
| Abstract | Background:
Obesity, characterized by excessive fat accumulation, represents a global health crisis closely linked to metabolic disorders such as type 2 diabetes, hypertension, and atherosclerosis. tRNA-derived small RNAs (tsRNAs) have recently emerged as important epigenetic regulators, yet their roles in fat deposition remain poorly characterized. This study aims to identify tsRNAs that influence fat accumulation and to elucidate their molecular mechanisms, with a focus on tRF‑Gly‑GCC‑037 (tRF‑Gly) as a candidate regulator of adipocyte differentiation. Methods: Visceral adipose tissue was collected from obese and lean pigs for comprehensive tRF and tiRNA sequencing. Differential expression analysis identified tRF‑Gly as a highly abundant candidate in obese samples. Functional assays in 3T3‑L1 preadipocytes included both overexpression and knockdown of tRF‑Gly, followed by lipid accumulation measurements and assessment of key adipogenic markers (CEBPα and PPARγ) by quantitative real-time PCR (qRT‑PCR) and western blot. Mechanistically, dual‑luciferase reporter assays, RNA immunoprecipitation (RIP), and nuclear–cytoplasmic protein fractionation were performed to examine how tRF‑Gly modulates the RAC1/JNK2/β‑catenin signaling axis. Results: tRF‑Gly was significantly upregulated in visceral adipose tissue from obese pigs and ranked among the most abundant tsRNAs. Overexpression of tRF‑Gly in 3T3‑L1 cells and in C57BL/6 mice promoted lipid accumulation and increased CEBPα and PPARγ expression, whereas tRF‑Gly knockdown reduced lipid deposition. Mechanistically, tRF-Gly was suggested to bind RAC1 mRNA with AGO3 involvement, leading to RAC1 silencing. Consistently, RAC1 knockdown phenocopied the adipogenic effects of tRF-Gly, whereas RAC1 overexpression reversed these effects. Furthermore, RAC1 deficiency disrupted the RAC1/JNK2/β‑catenin complex, impaired β‑catenin nuclear translocation, and suppressed Wnt/β‑catenin signaling. Conclusions: Our findings demonstrate that tRF‑Gly functions as a key regulator of fat accumulation. By silencing RAC1 via AGO3, tRF‑Gly disrupts RAC1/JNK2/β‑catenin complex assembly, prevents β‑catenin nuclear translocation, and downregulates Wnt/β‑catenin signaling, thereby promoting lipid deposition. This study uncovers a novel epigenetic mechanism by which tRF‑Gly controls fat accumulation and suggests that targeting tRF‑Gly may represent a therapeutic strategy for obesity and related metabolic disorders. | |
| Keywords | tRF-Gly, RAC1, RAC1/JNK2/β-catenin transport complex, Wnt/β-catenin signaling pathway, Fat deposition | |
| Address and Contact Information |
1 Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China 2 State Key Laboratory of Swine and Poultry Breeding Industry, Sichuan Agricultural University, Chengdu 611130, China 3 Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, China 4 Animal Disease Prevention and Green Development Key Laboratory of Sichuan Province, College of Life Sciences, Sichuan University, 610065 Chengdu, China *Corresponding author: Li Zhu zhuli@sicau.edu.cn Linyuan Shen shenlinyuan@sicau.edu.cn † Yuhang Lei, Mailin Gan and Kai Wang have contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 07 | DOI: 10.1186/s11658-025-00832-5 Volume 31 (2026) - 30:07 | |
| Title | CDCP1 ALLOSTERICALLY REGULATES THE AMPK α1 SUBUNIT TO ENHANCE FATTY ACID OXIDATION IN OSTEOBLASTS | |
| Authors | Xiang Li1,2†, Weichun Zhu3,4†, Jinlong Ma1,2, Zhenqian Sun1,2, Limin Wang5, Guangjun Jiao1,2*† and Yunzhen Chen1,2*† | |
| Abstract | Background:
Lipid metabolism disorders in osteoblasts may lead to osteoporosis. CUB domain-containing protein 1 (CDCP1) is associated with various intracellular signaling pathways. We investigated how CDCP1 regulates lipid metabolism and osteoblast function. Methods: This study utilized gene overexpression (via lentivirus) and loss-of-function (CRISPR/Cas9-mediated knockout) techniques to investigate the involvement of CDCP1 in lipid metabolism and osteogenesis. Transcriptomic and metabolomic analyses were performed to examine the mechanism of action of CDCP1. Furthermore, proximity ligation assays, GST pull-down, and molecular docking were employed to identify the interaction between CDCP1 and AMP-activated protein kinase (AMPK). Results: CDCP1 alleviated bone loss in mice. In vitro, CDCP1 promoted the phosphorylation of AMPK. Phosphorylated AMPK can enhance the activity of carnitine palmitoyltransferase, leading to increased fatty acid oxidation and promoting osteogenesis. Mechanistically, CDCP1 prevents the formation of the autoinhibitory conformation of the autoinhibitory domain by binding to the α3 helix, thereby protecting AMPK phosphorylation from self-inhibition. Conclusions: Our research revealed a new molecular mechanism linking CDCP1 and allosteric control of AMPK. These findings reveal for the first time the mechanism by which CDCP1 affects osteogenesis through lipid metabolism regulation, suggesting its potential as a therapeutic target for osteoporosis. | |
| Keywords | CDCP1, AMPK, Allosteric control, Fatty acid oxidation, Osteoblastic function | |
| Address and Contact Information |
1 Department of Orthopedics, Qilu Hospital of Shandong University, No.107, Wenhuaxi Road, Lixia District, Jinan 250000, China 2 The First Clinical College of Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China 3 State Key Laboratory for Innovation and Transformation of Luobing Theory, Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province, Jinan, Shandong, China 4 Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China 5 Department of Human Anatomy, Binzhou Medical University, Yantai, Shandong, China *Corresponding author: Guangjun Jiao jiaoguangjun@sdu.edu.cn Yunzhen Chen qilucyz@yeah.net † Guangjun Jiao and Yunzhen Chen have contributed equally as corresponding authors. † Xiang Li and Weichun Zhu have contributed equally as first authors. |
|
| Read full article at BMC | ||
| No. 14 | DOI: 10.1186/s11658-025-00840-5 Volume 31 (2026) - 30:14 | |
| Title | THE CANCER-TESTIS lncRNA LINC01940 PROMOTES GASTRIC CANCER MALIGNANT PROGRESSION AND CHEMORESISTANCE BY ENHANCING RIBOSOME BIOGENESIS VIA TAF15-MEDIATED NOL11 SUMOYLATION | |
| Authors | Weijie Zang1,2,3, Debiao Fan1,2,3, Zhuang Lu1,2,3,5, Xian Gao1,2,3, Danjie Xing1,2,3,6, Guangze Zhang1,2,3, Lei Liu2,4, Jianfeng Yi1,2,3, Junjie Chen2,3*, Yilin Hu1,2,3* and Wanjiang Xue1,2,3* | |
| Abstract | Background:
Aberrant ribosome biogenesis promotes gastric cancer (GC) progression and contributes to chemoresistance by sustaining protein synthesis, upon which GC cell survival depends. However, the regulatory role of cancer-testis-associated long noncoding RNAs (CT-lncRNAs) in modulating ribosome biogenesis in GC remains largely unexplored. Methods: First, we performed a screening of lncRNAs and identified CT-lncRNA LINC01940 on the basis of integrated expression and survival analyses using The Cancer Genome Atlas (TCGA) data. Subsequently, the impact of LINC01940 on GC progression and chemosensitivity was evaluated using in vitro cell functional assays, patient-derived organoid models, and in vivo subcutaneous tumor xenograft experiments. To further elucidate the underlying mechanisms, we employed a comprehensive approach combining bioinformatics analyses, RNA sequencing, fluorescence in situ hybridization, translation assays, ribosomal DNA (rDNA) transcription assays, methylated RNA immunoprecipitation, co-immunoprecipitation mass spectrometry, fluorescence multiplex immunohistochemistry, and RNA pull-down mass spectrometry. Results: Normally, testis-specific LINC01940 is aberrantly upregulated in GC and associated with poor prognosis. Functional assays demonstrated that LINC01940 promotes GC cell proliferation and invasion and confers resistance to cisplatin. Mechanistically, LINC01940 is stabilized by methyltransferase 16 (METTL16)/ insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3)-mediated N6-methyladenosine (m6A) modification, which enhances its ability to act as a scaffold promoting the interaction between the small ubiquitin-like modifier 2 (SUMO2) E3 ligase TATA-box binding protein associated factor 15 (TAF15) and Nucleolar protein 11 (NOL11), promoting the SUMOylation of NOL11 and enhancing its protein stability. This, in turn, increases ribosomal DNA transcription and ribosome biogenesis, thereby promoting GC progression and chemoresistance. Conclusions: LINC01940 is a cancer-testis lncRNA that promotes GC progression and cisplatin resistance by enhancing ribosome biogenesis via the METTL16/IGF2BP3–TAF15–NOL11 axis. These findings suggest its potential as a prognostic biomarker and therapeutic target in GC. | |
| Keywords | LINC01940, SUMOylation, Gastric cancer, Ribosome biogenesis, Cancer drug resistance | |
| Address and Contact Information |
1 Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Street, Nantong 226001, Jiangsu, China 2 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 Xisi Street, Nantong 226001, Jiangsu, China 3 Nantong Key Laboratory of Gastrointestinal Oncology, Nantong 226001, China 4 Department of Pathology, Affiliated Hospital of Nantong University, Nantong 226001, China 5 Department of Graduate School, Dalian Medical University, Dalian 116000, China 6 Department of General Surgery, Qidong People’s Hospital/Qidong Liver Cancer Institute/Affiliated Qidong Hospital of Nantong University, Nantong 226200, China *Corresponding author: Junjie Chen ntfyCJJ@ntu.edu.cn Yilin Hu hyl510@ntu.edu.cn Wanjiang Xue xuewanjiang@ntu.edu.cn † Weijie Zang, Debiao Fan, and Zhuang Lu contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 09 | DOI: 10.1186/s11658-025-00838-z Volume 31 (2026) - 30:09 | |
| Title | PCSK9 INHIBITION AMELIORATES MICROPLASTIC-INDUCED ENDOTHELIAL REDOX IMBALANCE VIA SIRT6 MODULATION | |
| Authors | Nunzia D’Onofrio1,5†, Isabella Donisi1†, Vitale Del Vecchio2, Francesco Prattichizzo3, Valeria Pellegrini3, Michelangela Barbieri4,5, Antonio Ceriello3, Raffaele Marfella4,5, Giuseppe Paolisso4,5† and Maria Luisa Balestrieri1,5*† | |
| Abstract | Background:
Microplastics (MPs) have emerged as significant environmental pollutants, posing a threat to ecosystems and humans. The presence of MPs in atherosclerotic plaques, exacerbating cardiovascular risk, has been recently reported. However, the molecular mechanism underlying the effects of MPs on the vascular endothelium are still undefined. In this regard, this study aims to investigate the effects of MPs on endothelial cell function and redox state and the underlying mechanisms. Methods: Immortalized human aortic endothelial cells (teloHAEC), human umbilical vein endothelial cells (HUVEC), and human coronary artery endothelial cells (HCAEC) were treated with MPs in the form of polyethylene (PE) and polyvinyl chloride (PVC) alone (70 µg/mL) or combined PE (30 µg/mL) + PVC (30 µg/mL) (PE + PVC) for up to 48 h. The effects of MPs on cell viability were evaluated using CCK-8, and its role in endothelial function was evaluated by flow cytometric analyses, enzyme-linked immunosorbent assays (ELISA), and XF HS Seahorse bioanalyzer. Proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and immunoblotting. Molecular involvement of sirtuin 6 (SIRT6) was investigated through gene silencing. Results: Our study demonstrated that PE and PVC, alone or in combination, upregulated inflammatory mediators monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM1), and intercellular adhesion molecule-1 (ICAM1) (p < 0.001), modulated the expression of autophagy markers anti-autophagy related 5 (ATG5) and p62, impaired mitochondrial metabolism by reducing maximal and basal respiration and adenosine triphosphate (ATP) production (p < 0.001), promoted reactive oxygen species (ROS) accumulation (p < 0.001) and cell cycle perturbations (p < 0.01), and increased apoptosis cell death (p < 0.001). These events were accompanied by a downregulation of sirtuin 6 (SIRT6) expression (p < 0.01) and an upregulation of PCSK9, at protein and messenger RNA (mRNA) levels (p < 0.01). Treatment with the PCSK9 inhibitor (iPCSK9) evolocumab ameliorated MP-induced cellular redox state imbalance, mitochondrial metabolism alteration, and SIRT6 downregulated levels (p < 0.01). SIRT6 transient silencing experiments denied the beneficial effects of iPCSK9 treatment, indicating that the pleiotropic functions of iPCSK9 may occur, at least in part, via modulation of SIRT6 and Forkhead box O3 (FOXO3A) expression levels. Conclusions: Overall, the results indicate that PCSK9 inhibition via evolocumab exhibits substantial promise in the prevention of MP-induced endothelial dysfunction, suggesting the PCSK9–SIRT6 axis as a new promising pathway to target in preventive strategies for cardiovascular risk caused by plastic pollution. | |
| Keywords | Microplastics, PCSK9 inhibition, Endothelial dysfunction, SIRT6, Inflammation | |
| Address and Contact Information |
1 Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy 2 Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Via Luciano Armanni 5, 80138 Naples, Italy 3 IRCCS MultiMedica, Via Fantoli 16/15, 20138 Milan, Italy 4 Department of Advanced Clinical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia, 80138 Naples, Italy 5 Research Center for Environmental Pollution and Cardiovascular Diseases, University of Campania Luigi Vanvitelli, Piazza Miraglia, 80138 Naples, Italy *Corresponding author: Maria Luisa Balestrieri marialuisa.balestrieri@unicampania.it † Nunzia D’Onofrio and Isabella Donisi share first authorship. † Giuseppe Paolisso and Maria Luisa Balestrieri contributed equally to this work and share last authorship. |
|
| Read full article at BMC | ||
| No. 10 | DOI: 10.1186/s11658-025-00836-1 Volume 31 (2026) - 30:10 | |
| Title | BEYOND THE MUTATIONS: SPATIOTEMPORAL REGULATION OF CFTR BY cAMP AND CALCIUM SIGNALING IN EPITHELIAL PHYSIOLOGY AND CYSTIC FIBROSIS | |
| Authors | Arpad Varga1,2,3, Aletta Kiss1,2,3, Tim Crul1,2,3, Tamara Madácsy1,2,3, Petra Pallagi1,2,3 and József Maléth1,2,3* | |
| Abstract | Cystic fibrosis (CF) is a life-shortening monogenic disease caused by mutations in the CFTR gene, but the functional expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl−/HCO3− channel is determined by more than its genetic sequence. Beyond the well-known folding defect of the common F508del mutation, CFTR activity is dynamically modulated by a network of intracellular signaling pathways that control the channel’s gating, trafficking to, and retention at the apical membrane. Foremost is the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway, which drives CFTR opening via phosphorylation of its regulatory (R) domain and coordination by scaffolding proteins (e.g., A-kinase anchoring proteins (AKAPs) and Na+/H+ exchanger regulatory factor 1 (NHERF1)). Equally important, Ca2+-dependent signaling cascades provide complementary fine-tuning: Ca2+-bound calmodulin can directly bind and increase the CFTR open probability, Ca2+-activated kinases such as Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the tyrosine kinase Pyk2 (with Src) can phosphorylate CFTR through noncanonical routes, and signaling intermediates such as IP3 receptor binding protein released with IP3(IRBIT) connect Ca2+ release to CFTR activation. These cAMP- and Ca2+-driven pathways intersect in specialized subcellular nanodomains, enabling precise spatiotemporal regulation of CFTR function. Clinically, although new CFTR modulator drugs have greatly improved outcomes, their effectiveness is limited by mutation-specific responses and incomplete restoration of channel activity. Understanding how cAMP–Ca2+ crosstalk governs CFTR in context can reveal novel therapeutic strategies targeting the channel’s regulatory microenvironment. This review highlights how compartmentalized cAMP and Ca2+ signals orchestrate CFTR function and discusses emerging approaches to harness this insight for better therapies across CF-affected organs. | |
| Keywords | Cystic fibrosis, CFTR regulation, cAMP signaling, Calcium signaling | |
| Address and Contact Information |
1 First Department of Medicine, University of Szeged, Szeged 6720, Hungary 2 HAS-USZ Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged 6720, Hungary 3 HCEMM-USZ Molecular Gastroenterology Research Group, University of Szeged, Szeged 6720, Hungary *Corresponding author: József Maléth jozsefmaleth1@gmail.com; maleth.jozsef@med.u-szeged.hu |
|
| Read full article at BMC | ||
| No. 12 | DOI: 10.1186/s11658-025-00833-4 Volume 31 (2026) - 30:12 | |
| Title | GPR43 DEFICIENCY AGGRAVATES SEPSIS BY PROMOTING GUT MICROBIOTA–DEPENDENT BARRIER DISRUPTION AND HIF-1α–ENO1 AXIS–MEDIATED M1 POLARIZATION OF MACROPHAGES | |
| Authors | Mingyang Tang1,2†, Hongru Li3†, Fei Tang4†, Yuanlong Shu1,2†, Bao Meng1,2, Qingyue Zhang1,2, Chengcheng Li1,2, Yuexin Xu1,2, Ying Xu1,2, Jingjing Pan1,2, Yanyan Liu1,2, Lifen Hu1,2, Cui Wang5*, Ting Wu1,2* and Jiabin Li1,2* | |
| Abstract | Background:
GPR43, a receptor for short-chain fatty acids (SCFAs), is broadly expressed in intestinal epithelial and immune cells and is essential for preserving barrier integrity and immune homeostasis. Nevertheless, how GPR43 influences gut microbiota composition and intestinal barrier integrity while also regulating macrophage immunometabolism in the context of sepsis remains poorly understood. Methods: A cecal ligation and puncture model was used to induce sepsis in mice. Survival, histopathology, and immune responses were compared between Gpr43−/− and wild-type mice; 16S ribosomal RNA (rRNA) sequencing and untargeted metabolomics were performed to evaluate gut microbiota composition and metabolic profiles. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation were used to assess functional impacts. Bone marrow-derived macrophages were employed to investigate the effects of GPR43 deficiency on macrophage polarization. RNA sequencing, metabolic flux analysis, and Western blotting were conducted to explore the molecular mechanisms involved. Peripheral blood mononuclear cell samples from patients with sepsis were analyzed for clinical correlation. Results: Gpr43−/− mice exhibited significantly reduced survival following CLP, along with impaired intestinal barrier function and elevated proinflammatory cytokine levels. Microbiota diversity and SCFA-producing bacteria were markedly decreased, accompanied by reduced SCFA levels in fecal metabolites. Fecal microbiota transplantation (FMT) partially restored gut function and survival in Gpr43−/− mice. GPR43-deficient macrophages displayed a strong M1-polarized phenotype with the upregulation of the glycolytic enzyme ENO1 and its upstream regulator HIF-1α. The inhibition of either ENO1 or HIF-1α reversed the proinflammatory phenotype. A clinical data analysis revealed that GPR43 expression was negatively correlated with IL-6, ENO1, and lactate levels. Conclusions: GPR43 exerts a dual protective role in sepsis by maintaining gut microbiota homeostasis and barrier integrity and by modulating macrophage metabolism and polarization via the HIF-1α–ENO1 axis. This study provides novel insights into the GPR43 in pathogenesis of sepsis and suggests potential therapeutic targets for intervention. | |
| Keywords | GPR43, Macrophage, Sepsis, Glycolysis, ENO1 | |
| Address and Contact Information |
1 Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China 2 Anhui Province Key Laboratory of Infectious Diseases, Anhui Medical University, Hefei 230022, China 3 Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China 4 Department of Interventional Pulmonology and Endoscopic Diagnosis and Treatment Center, Anhui Chest Hospital, Hefei 230022, China 5 Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China *Corresponding author: Cui Wang colorfulday23@126.com Ting Wu wutingf88945@163.com Jiabin Li lijiabin@ahmu.edu.cn † Mingyang Tang, Hongru Li, Fei Tang, and Yuanlong Shu contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 02 | DOI: 10.1186/s11658-025-00825-4 Volume 31 (2026) - 30:02 | |
| Title | MPP7 INHIBITS TUMOR METASTASIS THROUGH PROMOTING SNAIL DEGRADATION IN CLEAR CELL RENAL CELL CARCINOMA | |
| Authors | Mi Zhang1, Juan Zhang1, Yan Zhou1, Andi Zhao2, Hui Wang3, Bo Wang4, Juan Li4, Peijun Liu4* and Jin Yang1,3,5,6* | |
| Abstract | Background:
Tumor metastasis is a major factor of high recurrence and mortality in clear cell renal cell carcinoma (ccRCC), but its underlying mechanism remains elusive. This study focuses on investigating the impact and underlying molecular mechanisms of MAGUK p55 subfamily member 7 (MPP7) on the metastasis of ccRCC. Methods: The clinical significance of MPP7 in patients with ccRCC was investigated based on The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx) databases and clinical tissue samples. Slow aggregation, microscopic photography and immunofluorescence (IF) assay were applied to assess the effect of MPP7 on intercellular adhesion, cell morphology, and cytoskeletal F-actin, respectively. Transwell and wound-healing assays were used to detect cell migration and invasion. The quantitative real-time polymerase chain reaction (qRT-PCR), western blot, IF, co-immunoprecipitation (Co-IP), and immunoprecipitation-mass spectrometry (IP-MS) were applied to elucidate the underlying molecular mechanism. Conclusions: Our work elucidated the role and molecular mechanism of MPP7 in migration and invasion regulation of ccRCC. | |
| Keywords | Clear cell renal cell carcinoma, Ubiquitin–proteasome system, Epithelial–mesenchymal transition, MPP7, Snail | |
| Address and Contact Information |
1 Phase I Clinical Trial Ward, The First Affiliated Hospital of Xi’an Jiaotong University, No 277 Yanta West Road, Xi’an 710061, Shaanxi, China 2 Department of General Practice, The First Affiliated Hospital of Xi’an Jiaotong University, No 277 Yanta West Road, Xi’an 710061, Shaanxi, China 3 Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No 277 Yanta West Road, Xi’an 710061, Shaanxi, China 4 Translational Medicine Center, The First Affiliated Hospital of Xi’an Jiaotong University, No 277 Yanta West Road, Xi’an 710061, Shaanxi, China 5 Cancer Center, The First Affiliated Hospital of Xi’an Jiaotong University, No 277 Yanta West Road, Xi’an 710061, Shaanxi, China 6 Precision Medicine Center, The First Affiliated Hospital of Xi’an Jiaotong University, No 277 Yanta West Road, Xi’an 710061, Shaanxi, China *Corresponding author: Peijun Liu liupeijun@xjtu.edu.cn Jin Yang yangjin@xjtu.edu.cn |
|
| Read full article at BMC | ||
| No. 15 | DOI: 10.1186/s11658-025-00839-y Volume 31 (2026) - 30:15 | |
| Title | G-QUADRUPLEX STRUCTURES ARE KEY REGULATORS OF MAMMALIAN SPERMATOGENESIS | |
| Authors | Shuo Li1, Yixiao Ma1, Haoxin Shi1, Ruoyu Wang1, Chen Li1, Tian Zhang1, Chunyu Zhu3, Yanan Gu4, Ziyao Song1, Haoran Guo1, Mohan Dong2, Yu Li3, Zhen Li5, Ming-Qi Wang6, Weihong Wen7*, Fa Yang1* and Weijun Qin1* | |
| Abstract | Background:
Male infertility, impacting 8–12% of couples globally, often lacks clear etiology. G-quadruplexes (G4s), noncanonical DNA structures, are implicated in genomic regulation but remain underexplored in spermatogenesis. This study investigates G4 dynamics and their roles in male fertility. Methods: We employed antibody-based staining, cleavage under targets and tagmentation (CUT&Tag) sequencing, and a novel nanobody-based proximity labeling system (nanoG4BPL) to map G4 distribution and interacting proteins in mouse testicular cells. In vivo G4 stabilization with pyridostatin and clinical analysis of testicular tissues from patients with nonobstructive azoospermia (NOA) were conducted. Results: G4 structures are enriched in testicular tissues, displaying stage-specific dynamics during spermatogonial differentiation, meiosis, and spermiogenesis. Genome-wide profiling revealed the dual roles of G4s in coordinating gene expression with active epigenetic marks and facilitating genome architecture via CTCF interactions. G4 stabilization disrupted double-strand break repair during meiosis, with nanoG4BPL identifying Nijmegen breakage syndrome 1 (NBS1) as a G4-interacting protein promoting phase separation for homologous recombination. Clinically, patients with NOA exhibited significantly elevated G4 levels in spermatocytes. Conclusion: G4 structures are critical regulators of spermatogenesis, orchestrating gene expression, chromatin remodeling, and meiotic fidelity. Their dysregulation, particularly in patients with NOA, suggests a mechanistic link to male infertility, providing novel insights into its pathogenesis and highlighting potential avenues for future diagnostic or therapeutic exploration. | |
| Keywords | G-quadruplex, Spermatogenesis, DSB, HR, Male Infertility | |
| Address and Contact Information |
1 Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China 2 Department of Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China 3 Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, Shaanxi, China 4 Assisted Reproduction Center, Northwest Women and Children’s Hospital, Xi’an 710061, Shaanxi, China 5 Department of Human Anatomy, Histology and Embryology, Air Force Medical University, Xi’an 710032, Shaanxi, China 6 School of Pharmacy, Jiangsu University, Zhenjiang 212013, Jiangsu, China 7 Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, Shaanxi, China *Corresponding author: Weihong Wen weihongwen@nwpu.edu.cn Fa Yang yangfa@fmmu.edu.cn Weijun Qin qinwj@fmmu.edu.cn |
|
| Read full article at BMC | ||
| No. 16 | DOI: 10.1186/s11658-025-00848-x Volume 31 (2026) - 30:16 | |
| Title | MANY FACES OF MAMMALIAN NSD METHYLTRANSFERASES | |
| Authors | Eugenia A. Tiukacheva1,2, Yegor Vassetzky2,3*, Sergey V. Razin1,4, Dong Fang5 and Sergey V. Ulianov1,4* | |
| Abstract | Nuclear receptor-binding SET domain (NSD) proteins have been initially described as methyltransferases specific to lysine-36 in histone H3 and associated with active chromatin. However, their role in the regulation of transcription and in overall cellular physiology is much more complex, especially in mammals. The emerging diversity of their targets and, accordingly, the processes in which NSD proteins are involved, shows the importance of their noncanonical functions. A wide functionality apparently requires a complicated control system ensuring proper spatial and temporal activation of NSD methyltransferases. In this review, we discuss the role of NSD proteins in transcription, genome topology, mitosis, oncogenesis, immunity, DSB repair, and known mechanisms regulating their activity.
| |
| Keywords | NSD1, NSD2, NSD3, Histone methylation, H3K36me2, Chromatin structure | |
| Address and Contact Information |
1 Institute of Gene Biology, Moscow 119334, Russia 2 Koltzov Institute of Developmental Biology, Moscow 119334, Russia 3 CNRS UMR9018, Institut Gustave Roussy, 94805 Villejuif, France 4 Department of Molecular Biology, Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, Russia 5 Life Sciences Institute, Zhejiang University, Hangzhou 310058, Zhejiang, China *Corresponding author: Yegor Vassetzky yegor.vassetzky@gustaveroussy.fr Sergey V. Ulianov sergey.v.ulyanov@gmail.com |
|
| Read full article at BMC | ||
| No. 17 | DOI: 10.1186/s11658-025-00842-3 Volume 31 (2026) - 30:17 | |
| Title | TARGETING INTEGRIN αVβ3–Ptgs2–mTOR SIGNALING RESCUES BONE FORMATION IN OSTEOPOROSIS: FROM MOLECULAR MECHANISM TOWARD THERAPY | |
| Authors | Changshun Chen1,2,3†, Jinyi Gu4†, Chenhui Yang1,2†, Fei Yang1,2, Zirui Liu1,2, Lei Wen1,2,3, Rongjing Chen1,2, Bin Geng1,2* and Yayi Xia1,2* | |
| Abstract | Background:
Integrin αVβ3, a key ECM receptor, is essential for bone metabolism, yet its role in postmenopausal osteoporosis (PMOP) remains unclear. This study investigates the molecular mechanisms by which integrin αVβ3 regulates osteoblast function and bone homeostasis in PMOP. Methods: Using clinical samples, OVX mice, and in vitro models, we analyzed integrin αVβ3 expression and its impact on osteogenesis. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated knockout, multi-omics profiling, and protein interaction assays (Co-IP, BLI, and structural modeling) were employed to dissect the underlying pathway. An AAV9-based in vivo overexpression system was developed to evaluate therapeutic potential. Results: Integrin αVβ3 was downregulated in PMOP patients and OVX mice, correlating with osteoblast dysfunction and reduced bone formation. Mechanistically, integrin αVβ3 deficiency upregulated Ptgs2, which directly bound to mammalian target of rapamycin (mTOR) via a hydrogen bond between Ptgs2-Glu52 and mTOR-Ser2159, inhibiting mTOR phosphorylation. This suppression disrupted mTORC1-S6K/4EBP1 signaling, impairing osteoblast proliferation and survival. Notably, AAV9-mediated integrin αVβ3 overexpression rescued bone loss in OVX mice. Conclusions: Our findings unveil a novel integrin αVβ3–Ptgs2–mTOR axis in PMOP pathogenesis: estrogen deficiency reduces integrin αVβ3, enabling Ptgs2-mediated mTOR inhibition and osteogenic decline. This study identifies integrin αVβ3 as a potential therapeutic target to restore bone formation in osteoporosis. | |
| Keywords | Integrin αVβ3, Ptgs2, MTOR signaling, Postmenopausal osteoporosis, Osteoblast dysfunction | |
| Address and Contact Information |
1 Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China 2 Orthopedic Clinical Medical Research Center and Intelligent Orthopedic Industry Technology Center of Gansu Province, Lanzhou 730030, China 3 Department of Orthopedics and Trauma Surgery, Affiliated Hospital of Yunnan University, Kunming 650032, China 4 Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730030, China *Corresponding author: Bin Geng gengbing2024@163.com Yayi Xia xiayay@163.com † Changshun Chen, Jinyi Gu, Chenhui Yang contributed equally to this work and shared the first authorship. |
|
| Read full article at BMC | ||
| No. 18 | DOI: 10.1186/s11658-025-00834-3 Volume 31 (2026) - 30:18 | |
| Title | THE NEURO-IMMUNE INSIGHTS OF ITCH: PERIPHERAL MECHANISMS AND CENTRAL GLIAL CONTRIBUTIONS | |
| Authors | Zhe Li1,2†, Ning Yu3,4†, Sidi Feng5†, Xinrui Wang6†, Yu-Xia Chu7* and Xiaowen Liu1* | |
| Abstract | Itch is a common symptom of inflammatory, systemic, and neurological conditions and is often driven by persistent neuroinflammatory processes. This review explores the intricate mechanisms underlying itch, focusing on interactions among sensory neurons, immune mediators, and glial cells. Key peripheral pathways include activation of pruriceptors by histamine, interleukins, and chemokines, as well as inflammatory pathways dependent on Toll-like receptors (TLRs). These pathways promote the release of mediators such as interleukin-6 (IL-6) and C–C motif chemokine ligand 2 (CCL2). In the spinal cord, astrocytes and microglia contribute to itch amplification by releasing proinflammatory cytokines and activating signaling pathways such as signal transducer and activator of transcription 3 (STAT3) and TLR4. These processes drive central sensitization and facilitate the transition from acute to chronic itch in conditions such as atopic dermatitis, psoriasis, and allergic contact dermatitis. By summarizing advances in neuroimmune crosstalk and glial–neuronal interactions, this review identifies potential molecular targets for therapeutic strategies aimed at alleviating itch and improving patient outcomes. | |
| Keywords | Itch, Pruriceptors, Immune receptors, Glial cells | |
| Address and Contact Information |
1 Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, China 2 Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China 3 State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Human Anatomy, Histology and Embryology, Joint Laboratory of Anesthesia and Pain, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Neuroscience Center, Union Medical College, Beijing, China 4 Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China 5 Dalian Medical University, Dalian, China 6 Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China 7 Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Institute of Acupuncture Research, Institutes of Integrative Medicine, Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Shanghai Medical College, Fudan University, Shanghai 200032, China *Corresponding author: Yu-Xia Chu yuxiachu@fudan.edu.cn Xiaowen Liu liuxiaowen@cjfh.org.cn † Zhe Li, Ning Yu, Sidi Feng, and Xinrui Wang have contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 19 | DOI: 10.1186/s11658-025-00844-1 Volume 31 (2026) - 30:19 | |
| Title | THE MULTIPLE ROLES OF gt1-Cre IN THE GENERATION OF TRANSGENIC MICE | |
| Authors | Ze-Sen Feng1†, Jie Luo1†, Xiao-Cui Chen1†, Ping-Ping Zhao1, Shi-Tong Qiu1, Chun-Yu Wu1, Xiao-Rong Huang1, Bing-Chun Sun2, Xiao-Jun Guo1, Zhen-Nan Ye1*, Chen Yang1*, Hua-Feng Liu1* and Ji-Xin Tang1* | |
| Abstract | The Cre/loxP system continues to serve as a well-established and widely adopted strategy for generating conditional gene knockout or knock-in mouse models, facilitating precise genetic manipulations. The Ggt1 gene, which exhibits specific expression in proximal tubular epithelial cells (TECs) of the kidney, has been extensively employed as a Cre driver for tissue-specific gene targeting within these cells. In this study, to achieve conditional Fam134b knockout in proximal TECs, we generated Fam134b floxed mice and crossed them with Ggt1-Cre transgenic mice. After several generations of selective breeding, we successfully obtained conditional Fam134b knockout mice, which displayed specific deletion of the target gene in proximal TECs. This was confirmed by western blot analysis, which demonstrated a marked deficiency of the FAM134B protein in the renal cortex of these mice. During the mating experiments, we unexpectedly found that we could obtain systematic Fam134b knockout mice, suggesting that Ggt1-Cre might be expressed and functional in germ cells. Genomic and transcriptomic sequencing analysis unequivocally confirmed the deletion of exon 4, while western blot analysis revealed complete absence of FAM134B protein in both heart and kidney tissues of these knockout mice. Through the implementation of different mating strategies, we determined that Ggt1-Cre mediated gene knockout occurs in germ cells that have completed the first meiotic division, rather than in germ cells prior to this developmental stage. Furthermore, qPCR and western blot analyses demonstrated the expression of Cre driven by the Ggt1 promoter in both testes and ovaries, providing additional evidence for its germline activity. Lineage tracing experiments revealed that Ggt1-Cre is expressed in both the kidneys and testes of B6-G/R f/+; Ggt1-Cre transgenic mice, where it effectively catalyzes Cre recombinase activity, leading to the conversion of green fluorescent protein-expressing cells to red fluorescent protein-expressing cells. These findings collectively highlight that Ggt1-Cre is not only a reliable proximal TEC-specific Cre driver but also an effective germline-specific Cre driver. Consequently, it can be utilized to achieve gene knockout or overexpression in both proximal TECs and post-first meiotic division germ cells, thereby enabling in-depth in vivo functional studies of genes in these distinct cell types. | |
| Keywords | Cre/loxP system, CRISPR/Cas9, FAM134B, Gene knockout, Gene knock-in, Ggt1-Cre | |
| Address and Contact Information |
1 Department of Nephrology, National Clinical Key Specialty Construction Program (2023), Institute of Nephrology, Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China 2 Department of Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China *Corresponding author: Zhen-Nan Ye yezhennan12@mails.ucas.ac.cn Chen Yang yangchen307@126.com Hua-Feng Liu liuhf@gdmu.edu.cn Ji-Xin Tang tangjixin@gdmu.edu.cn † Ze-Sen Feng, Jie Luo and Xiao-Cui Chen have contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 13 | DOI: 10.1186/s11658-025-00809-4 Volume 31 (2026) - 30:13 | |
| Title | MITOCHONDRIA–ENDOPLASMIC RETICULUM CONTACT SITES IN HEPATOCYTIC SENESCENCE | |
| Authors | Pavitra Kumar1, Mohsin Hassan1, Frank Tacke1 and Cornelius Engelmann1,2* | |
| Abstract | Inter-organelle communication via membrane contact sites (MCSs) is essential for the efficient functioning of eukaryotic cells, facilitating coordination among approximately 20 distinct organelles, each with unique metabolic profiles. Among these interactions, mitochondria–endoplasmic reticulum (ER) contacts (MERCs) are particularly significant, encompassing about 5% of the mitochondrial surface. Key proteins involved in MERCs include inositol 1,4,5-trisphosphate receptor (IP3R), voltage-dependent anion channel (VDAC), glucose-regulated protein 75 (GRP75), Sigma1 receptor (Sig-1R), vesicle-associated membrane protein (VAMP)-associated protein B (VAPB), protein deglycase DJ-1, and protein tyrosine phosphatase interacting protein 51 (PTPIP51), with new proteins continually being identified for their roles in these structures. At these contact sites, metabolic exchanges involve calcium (Ca2+), lipids, reactive oxygen species (ROS), and proteins. MERCs enable efficient molecular exchanges through temporary bridges mainly formed by the ER, the organelle with the largest surface area. These contacts are crucial for maintaining mitochondrial dynamics, which is essential for cellular homeostasis, and they are notably impacted in pathological states such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver diseases (ALD), and viral hepatitis. Dysfunctional MERCs can lead to mitochondrial fragmentation, increased ROS production, impaired autophagy, and disrupted protein trafficking, thereby exacerbating senescence and cellular aging. Senescence is a cell fate initiated by stress, characterized by stable cell-cycle arrest and a hypersecretory state, and is an underlying cause of aging and many chronic conditions, including liver diseases. The hallmarks of senescence—such as macromolecular damage, cell cycle withdrawal, deregulated metabolism, and a secretory phenotype—are well established. However, recent studies have demonstrated that senescence is a heterogeneous process, with molecular markers varying according to the stressors that induce it. This review focuses on the functional aspects of MERCs in hepatic senescence and their impact on liver diseases, and explores the potential of targeting MERCs to address hepatocytic senescence. | |
| Keywords | Mitochondria, ER, Contact sites, MERCs, Calcium, Hepatocyte, Senescence | |
| Address and Contact Information |
1 Department of Hepatology and Gastroenterology, Medizinische Klinik M. S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin - Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany 2 Berlin Institute of Health (BIH), 10178 Berlin, Germany *Corresponding author: cornelius.engelmann@charite.de |
|
| Read full article at BMC | ||
| No. 05 | DOI: 10.1186/s11658-025-00818-3 Volume 31 (2026) - 30:05 | |
| Title | METHYLATION-INDUCED SILENCING OF AZGP1 ENHANCES PROSTATE CANCER METASTASIS BY STIMULATING TUMORAL GLYCOLYSIS | |
| Authors | Lu Li1†, Jinguang Luo2†, Linyue Zhao1†, Lu Tian3†, Jianfeng Wang4*, Yifei Cheng5* and Xiao Li6,7* | |
| Abstract | Background:
Metastasis is the primary cause of mortality in patients with prostate cancer (PCa), yet effective treatments remain scarce. Identifying reliable biomarkers and understanding their underlying mechanisms is crucial for advancing clinical management. Methods: Firstly, we integrated single-cell and bulk transcriptomic data and employed the Scissor tool to characterize tumor cells with metastatic advantages (termed metastatic cells). Then, independent predictive genes for metastasis were identified through univariate and multivariate regression analyses. The role of hub genes in PCa metastasis was further validated using multiple large datasets, malignant phenotype experiments, in vivo metastatic models, and a clinical-sample-based immunohistochemical cohort. Further, we explored the metabolic characteristics related to hub genes through unbiased functional annotation, and validated the upregulated glycolysis by measuring l-lactic acid production, extracellular acidification rates (ECAR), and oxygen consumption rates (OCR). Finally, multi-omics data were employed to investigate the promoter-methylation-dependent regulation of alpha-2-glycoprotein 1 (AZGP1) transcription, with methylation confirmed through PCa cell-based methylation-specific PCR (MSP) assays. Results: AZGP1 was identified as an independent protective predictor of metastasis, which was validated in vitro and in vivo. Metabolic functional annotation revealed that glycolysis was upregulated in AZGP1-positive luminal cells. Consistently, overexpression of AZGP1 in PCa cells was associated with lower l-lactic acid levels, reduced ECAR, and increased OCR. In addition, DNA methylation at the cg26429636 region was linked to decreased transcriptional expression of AZGP1. MSP assays revealed an unmethylated pattern in PCa cells with high AZGP1 expression, and higher methylation levels in AZGP1-low cells. Conclusions: Promoter methylation of AZGP1 leads to reduced transcriptional expression, thereby promoting glycolysis in tumor cells and facilitating metastasis. The detection of AZGP1 methylation levels offers a valuable reference for dynamic surveillance of PCa metastasis. | |
| Keywords | Prostate cancer, Metastasis, AZGP1, Glycolysis | |
| Address and Contact Information |
1 Department of Pathology, Nanjing Drum Tower Hospital, Affliated Hospital of Medical School, Nanjing University, Nanjing 210008, China 2 Department of Urology, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China 3 State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau 999078, China 4 Department of Urology, China–Japan Friendship Hospital, Beijing 100029, China 5 Department of Urology, Southeast University Zhongda Hospital, Nanjing 210009, China 6 Department of Urologic Surgery, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China 7 Department of Scientific Research, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China *Corresponding author: Jianfeng Wang zryhyy1@126.com Yifei Cheng yifei_cheng@163.com Xiao Li leex91@163.com † Lu Li, Jinguang Luo, Linyue Zhao, Lu Tian contributed equally to this work. |
|
| Read full article at BMC | ||
| No. 21 | DOI: 10.1186/s11658-025-00853-0 Volume 31 (2026) - 30:21 | |
| Title | TGFβ PATHWAY REPRESSES HEPATIC RIBOSOME BIOGENESIS AND PROTEIN SYNTHESIS BY REGULATING p70S6K–S6RP PROTEINS | |
| Authors | Athanasios Stavropoulos1*, Vassiliki Stamatopoulou2, Eleftherios Pavlos1,3, Maria Manioudaki1, Stratigoula Sakellariou4, Constantinos Stathopoulos2 and Maria Xilouri1 | |
| Abstract | Background:
Transforming growth factor-beta (TGFβ)-superfamily signaling has been implicated in the regulation of hepatocyte growth and regeneration after acute or chronic liver injury. However, the precise mechanisms underlying TGFβ signaling in the distinct hepatic cell types during the progression of liver fibrosis remain largely unknown. We aim to identify the downstream molecular mechanisms of TGFβ-signaling modulation on hepatocytes. Methods: To modulate TGFβ-superfamily signaling in vivo, Smad3 or Smad7 were adenovirally overexpressed in mouse liver. Parallelly, hepatosphere cultures were treated with recombinant TGFβ1 and subjected to transcriptomic analysis. These data were compared with transcriptomes from Smad7-overexpressing livers. To broaden the analysis, publicly available RNA-seq datasets from TGFβ-treated hepatic stellate cells and hepatocellular carcinoma lines were meta-analyzed. Finally, human liver tissues from cirrhotic and healthy individuals were examined for fibrosis and ribosome biogenesis markers to validate murine findings. Results: Acute hepatic overexpression of Smad3 induced a transient fibrotic phenotype in the mouse liver. In hepatosphere cultures, TGFβ1 treatment suppressed key components of ribosomal assembly, whereas Smad7 overexpression exerted the opposite effect in the mouse liver, thus highlighting ribosome biogenesis as a major cellular process negatively regulated by the TGFβ superfamily. Inhibition of TGFβ signaling via Smad7 increased hepatic protein content (a critical parameter for restoring hepatic homeostasis upon liver damage), activated the nucleolus, and prompted the production of ribosomal pre-mRNAs without affecting p53 levels. Mechanistically, SMAD7-mediated inactivation of TGFβ signaling triggered selectively the p70S6K–S6RP regulatory axis, independently of cellular myelocytomatosis oncogene (c-MYC), mechanistic target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK) pathways. Importantly, analysis of hepatic tissue from cirrhotic patients and controls unveiled a negative association between TGFβ signaling and ribosome biogenesis in fibrotic livers. Complementary meta-analysis of RNA-seq data demonstrated that TGFβ regulates ribosome biogenesis in a cell type-specific manner, suppressing it in hepatocytes while enhancing it in hepatic stellate cells, consistent with their distinct functional states and transcriptional landscapes. Conclusions: Collectively, our data reveal a SMAD-dependent regulatory role of TGFβ-superfamily signaling on hepatocytes that is tightly connected with hepatic growth to ensure proper energy homeostasis and metabolism. This is a critical regeneration parameter, which is closely related to the restoration of hepatic mass, especially following liver injury and fibrosis. | |
| Keywords | Cell signaling, Cirrhosis, Liver growth, Regeneration, Ribosome, Smads, Translation | |
| Address and Contact Information |
1 Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece 2 Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece 3 Division of Basic Sciences, School of Medicine, University of Crete, Heraklion, Greece 4 First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece *Corresponding author: Athanasios Stavropoulos astavrop@bioacademy.gr |
|
| Read full article at BMC | ||
| No. 08 | DOI: 10.1186/s11658-025-00837-0 Volume 31 (2026) - 30:08 | |
| Title | HETEROGENEITY OF GLUCOSE METABOLISM AND UPTAKE IDENTIFIES DISTINCT CANCER CELL AND CANCER STEM CELL PHENOTYPES | |
| Authors | Zuzana Tylichova1*, Martin Krkoska1, Vaclav Hrabal1, Michaela Stenckova1, Borivoj Vojtesek1 and Philip J. Coates1* | |
| Abstract | Background:
Tumor cells show phenotypic heterogeneity, including a small subpopulation of cancer stem-like cells (CSCs) that are responsible for maintaining tumor growth and metastasis. Altered glucose metabolism is a characteristic feature of cancer cells, which often display increased aerobic glycolysis alongside mitochondrial oxidative respiration (the Warburg effect). However, there is evidence that CSCs exhibit distinct glucose metabolism compared with the tumor cell bulk, with increased mitochondrial activity and oxidative respiration. Thus, identifying individual cells with different modes of glucose metabolism may serve as a common identifier of CSCs, and these metabolic differences would allow selective therapeutic targeting. Methods: We investigated the levels of enzymes involved in glycolysis and oxidative respiration, together with glucose uptake and mitochondrial membrane potential in individual cancer cells. These parameters were correlated with each other and with CSC markers. Results: We show considerable heterogeneity of metabolic markers in individual tumor cells. Surprisingly, high glucose uptake correlates with high mitochondrial membrane potential, indicating that increased oxidative respiration and aerobic glycolysis coexist rather than showing an inverse correlation. We also show that colonies derived from cells with high mitochondrial membrane potential exhibit heterogeneous metabolic parameters, demonstrating that metabolic profiles are not hard-wired. Public gene expression profiling data indicated similar inconsistent metabolic features of CSCs. Conclusions: The data reveal inherent heterogeneity and plasticity of glucose metabolism and mitochondrial membrane potential in tumor cells, with evidence for a subpopulation that possesses both increased glucose uptake and increased mitochondrial membrane potential, with implications for therapeutic targeting of metabolism in cancer. | |
| Keywords | Glucose metabolism, Cancer stem cells, Mitochondria, ALDH, LDH, SDH, GLUT1 | |
| Address and Contact Information |
1 RECAMO, Masaryk Memorial Cancer Institute, Zluty Kopec 7, Brno 656 53, Czech Republic *Corresponding author: Zuzana Tylichova zuzana.tylichova@mou.cz Philip J. Coates philip.coates@mou.cz |
|
| Read full article at BMC | ||
| No. 11 | DOI: 10.1186/s11658-025-00846-z Volume 31 (2026) - 30:11 | |
| Title | INHIBITION OF THE RORC/GPX4 MEDIATED FERROPTOSIS REGULATORY AXIS SUPPRESSES TUMOR GROWTH AND ALLEVIATES ENZALUTAMIDE RESISTANCE IN PROSTATE CANCER | |
| Authors | Yan Li1,2†, Bingqi Zhang2†, Zhongmin Zhang1,2, Wei Yan1,2, Haoyu Wang1,2, Xun Xu1,2, Anqi Lv2, Zhengming Liao1,2* and Lang Guo1,2* | |
| Abstract | Background:
Patients with castration-resistant prostate cancer (CRPC) often develop resistance following long-term enzalutamide treatment. Building upon previous research, we aims to further explore the effect of ilicicolin A (ili-A) on enzalutamide resistance and to elucidate the underlying resistance mechanisms. Methods: Proliferation, migration, and invasion of prostate cancer (PCa) cells were evaluated by 5-ethynyl-2′-deoxyuridine (EdU) assays, colony formation, scratch, and Transwell. Cell Counting Kit 8 (CCK-8) was used to assess the efficacy of drug inhibition in CRPC cells. The expression of tumor cell apoptotic proteins and ferroptosis was assessed using western blot (WB) analysis. Coimmunoprecipitation (Co-IP) and proximity ligation assay (PLA) were used to identify the mechanism of interaction between ilicicolin A and ferroptosis. Tumor transplantation experiments with mice were conducted to confirm findings. Results: Ili-A showed dose-dependent inhibition of PCa cells including C4-2B and 22Rv1 cell lines. The overexpression of the RORC gene activated the expression of ferroptosis-related proteins, such as FTH1, GPX4 and SLC7A11, and enhanced proliferation of PCa cells. WB experiments indicated that RORC upregulated AR and AR-V7. An enzalutamide-resistant C4-2B cell line revealed that RORC serves as a gene target for enzalutamide resistance. Finally, it was observed that ili-A could suppress CRPC cells proliferation by downregulating RORC expression, thereby promoting ferroptosis and enhancing the sensitivity to enzalutamide. Conclusions: Ili-A inhibited RORC expression, increased malondialdehyde (MDA) content, suppressed glutathione (GSH) production, released free Fe2+, increased reactive oxygen species (ROS), activated the ferroptosis pathway, enhanced enzalutamide sensitivity, and inhibited CRPC cell proliferation. Furthermore, ili-A enhances the interaction between ROR-γ and GPX4.
| |
| Keywords | Castration-resistant prostate cancer, Ilicicolin A, Ferroptosis, Enzalutamide, Drug resistance, Orphan nuclear receptor | |
| Address and Contact Information |
1 Department of Urology, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Sizhen Laboratory, Hubei University of Chinese Medicine, Wuhan 430000, Hubei, China 2 Hubei University of Chinese Medicine, No.1, Tanhualin, Wuchang District, Wuhan 430000, Hubei, China *Corresponding author: Zhengming Liao lzmwhu@163.com Lang Guo guol199110@163.com † Yan Li and Bingqi Zhang contributed equally to this work and are co-first authors for this paper. |
|
| Read full article at BMC | ||
| No. 20 | DOI: 10.1186/s11658-026-00859-2 Volume 31 (2026) - 30:20 | |
| Title | TSP50 ATTENUATES METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE VIA SCD1 DEGRADATION-MEDIATED SUPPRESSION OF HEPATOCYTE LIPOGENESIS | |
| Authors | Jiujia Liang1,2,3, Zhihui Luan4, Rong Jin2, Rina Su1, Jiarong Ge4, Xiao Tian1, Chunxue Niu1, Jiawei Li1, Xiaoli Li2, Feng Gao3, Zhenbo Song1, Luguo Sun1, Guannan Wang3, Lihua Zheng3, Ying Sun2, Lei Liu3, Yongli Bao3, Shuyue Wang1 & Xiaoguang Yang2 | |
| Abstract | Background:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to chronic liver disease worldwide, yet the molecular mechanisms driving its pathogenesis remain incompletely defined. Although dysregulated hepatic lipogenesis is a well-established driver of MASLD progression, the role of testes-specific protease 50 (TSP50)—an enzyme with demonstrated oncogenic functions in multiple cancers—in hepatic lipid metabolism and its potential involvement in the development of MASLD remains unexplored. Methods: The study utilized the STelic Animal Model (STAM) along with high-fat/high-cholesterol plus fructose (HFF) and methionine-choline deficient (HFMCD) dietary models to evaluate the functional role of TSP50 in MASLD progression. Hepatocyte-specific knockout and AAV-mediated TSP50 reconstitution were performed to assess cell-autonomous effects. Mechanistic insights were gained through biochemical analyses of lipid metabolism pathways and protein interaction studies. Results: TSP50 deficiency markedly accelerated MASLD progression across all experimental models, promoting hepatic steatosis, inflammation and fibrosis while increasing susceptibility to hepatocellular carcinoma (HCC). Conversely, TSP50 supplementation exerted protective effects against MASLD development. Furthermore, we identified a novel regulatory mechanism whereby TSP50 directly interacts with and degrades stearoyl-CoA desaturase 1 (SCD1) through its catalytic hydrolase activity, thereby suppressing de novo lipogenesis. The inhibitor of SCD1 rescued hepatic TSP50 knockout induced lipid accumulation and liver injury during MASLD. Conclusions: Our study reveals the role of TSP50 in hepatic lipid metabolism, identifying it as a novel regulator of hepatic de novo lipogenesis that exerts protective effects against MASLD through catalytic degradation of SCD1. These findings not only advance our understanding of MASLD pathogenesis but also offer novel insights for developing therapeutic strategies. | |
| Keywords | TSP50, SCD1, Protease, MASLD, Hepatocyte lipid accumulation | |
| Address and Contact Information |
1 National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China 2 China International Joint Research Center for Human Stem Cell Bank, Northeast Normal University, Changchun 130024, China 3 Key Laboratory of Molecular Epigenetics, Institute of Genetics and Cytology, Ministry of Education, Northeast Normal University, Changchun 130024, China 4 School of Life Sciences, Changchun Normal University, Changchun 130032, China *Corresponding author: Shuyue Wang wangsy171@nenu.edu.cn Xiaoguang Yang yangxg168@nenu.edu.cn |
|
| Read full article at BMC | ||
| No. 22 | DOI: 10.1186/s11658-026-00867-2 Volume 31 (2026) - 30:22 | |
| Title | THE PROMOTING ROLES OF GLP1R AND GIPR IN STEMNESS MAINTENANCE AND MULTIPLE LINEAGE-SPECIFIC DIFFERENTIATION OF PDLSCs | |
| Authors | Yifen Shen1†, Mengjie Zhang3†, Tao Yang4, Yuxiang Wu5, Yinfeng Qiu6, Le Zhang2,7, Fei Li8, Minjie Chen3, Qili Chen9*, Wenbin Wei3*, Hua Li2,7* and Yihang Shen1* | |
| Abstract | Background:
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adverse factors in the periodontal microenvironment. Therefore, identifying novel therapeutic targets and elucidating the underlying molecular mechanisms to protect the proliferative and differentiation potential of PDLSCs is of significant importance. Methods: PDLSCs were exposed to electronic cigarette extract and various common oral stressors to evaluate the expression of glucagon such as peptide 1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR). PDLSCs isolated from patients with periodontitis and PDLSCs from a mouse periodontitis model were also analyzed. Functional studies were performed by GLP1R or GIPR knockdown, overexpression, and treatment with single or dual receptor agonists, followed by assessment of cell proliferation and multilineage differentiation capacities. Transcriptome (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and RNA immunoprecipitation sequencing (RIP-seq) were applied to delineate downstream signaling pathways and RNA–protein interactions. Protein synthesis regulation was further investigated by immunoprecipitation of interferon induced protein with tetratricopeptide repeats (IFIT)-associated translation initiation factors. For in vivo validation, wild-type and GLP1R/GIPR double-knockout periodontitis mice were transplanted with CRISPR-Cas9 mCherry-labeled PDLSCs and treated with receptor agonists. Disease severity and PDLSC fate were evaluated by histology and lineage tracing. Finally, a questionnaire-based survey was conducted in 150 patients with periodontitis, including 74 individuals with long-term use (> 1 month) of GLP1R or GLP1R/GIPR dual agonists (e.g., semaglutide, liraglutide, tirzepatide), to assess their periodontal outcomes. Results: GLP1R and GIPR expression were markedly downregulated in PDLSCs exposed to multiple stressors and in PDLSCs isolated from periodontitis specimens. RNA-seq, ChIP-seq, and RIP-seq identified downstream pathways and RNA–protein interactions implicated in receptor-mediated regulation. Functionally, GIPR agonism promoted PDLSC proliferation via activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, whereas GLP1R agonist enhanced multilineage differentiation capacity in vitro. Mechanistically, GLP1R knockdown induced robust upregulation of IFIT1/2/3, while GLP1R agonist suppressed IFIT expression. IFIT1/2/3 were shown to interact with eIF3C and to inhibit translation of differentiation-related mRNAs, linking GLP1R signaling to translational control of PDLSC fate. In vivo, transplantation experiments in both wild-type and GLP1R/GIPR double-knockout periodontitis mice demonstrated that single and dual receptor agonists significantly improved endogenous and exogenous PDLSC-mediated periodontal regeneration. Consistently, a clinical survey of 150 patients with periodontitis (74 receiving GLP1R or dual agonists) revealed significantly better periodontal staging and grading in treated individuals, with longer agonist exposure associated with greater improvement. Conclusions: Our findings uncover the different molecular roles of GIPR and GLP1R in self-renewal capacity and multipotency of PDLSCs, and open new avenues for developing therapeutic targets and strategies in oral tissue engineering and regenerative medicine. | |
| Keywords | PDLSC, GLP1R, GIPR, MAPK/ERK, IFIT | |
| Address and Contact Information |
Central Laboratory, Suzhou Ninth People’s Hospital, Soochow University, 2666 Ludang Road, Suzhou 215200, Jiangsu, China 2 Jiangsu Province Engineering Research Center of Development and Translation of Key Technologies for Chronic Disease Prevention and Control, Suzhou Vocational Health College, 28 Kehua Road, Suzhou 215009, Jiangsu, China 3 Department of Oral Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People’s Hospital; National Center for Stomatology, and National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, 639 Zhizaoju Road, Shanghai 200023, China 4 Department of Medical Cosmetology, Suzhou Ninth People’s Hospital, Soochow University, Suzhou 215200, Jiangsu, China 5 Department of Pathology, Suzhou Ninth People’s Hospital, Soochow University, Suzhou 215200, Jiangsu, China 6 Department of Stomatology, Suzhou Ninth People’s Hospital, Soochow University, Suzhou 215200, Jiangsu, China 7 Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China 8 Department of Preventive Dentistry, Shanghai Jiao Tong University School of Medicine Affiliated Ninth People’s Hospital; National Center for Stomatology, and National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, 639 Zhizaoju Road, Shanghai 200023, China 9 School of Pharmacy, China Medical University, 77 Puhe Road, Shenyang 110122, Liaoning, China *Corresponding author: Qili Chen qlchen@cmu.edu.cn Wenbin Wei tian_qian_cool@126.com Hua Li kaikaixinxin@sjtu.edu.cn Yihang Shen devbrother@sjtu.edu.cn † Yifen Shen and Mengjie Zhang have contributed equally to this work. |
|
| Read full article at BMC | ||