Cell Reports Medicine最新文献_第4页

Leucine restriction ameliorates Fusobacterium nucleatum-driven malignant progression and radioresistance in nasopharyngeal carcinoma. 限制亮氨酸可改善分枝杆菌核酸瘤驱动的鼻咽癌恶性进展和放射抗性。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 Epub Date: 2024-10-01 DOI: 10.1016/j.xcrm.2024.101753

Songhe Guo, Shan Xing, ZhenYu Wu, Fangfang Chen, Xiaoyun Pan, Qifan Li, Wanli Liu, Ge Zhang

{"title":"Leucine restriction ameliorates Fusobacterium nucleatum-driven malignant progression and radioresistance in nasopharyngeal carcinoma.","authors":"Songhe Guo, Shan Xing, ZhenYu Wu, Fangfang Chen, Xiaoyun Pan, Qifan Li, Wanli Liu, Ge Zhang","doi":"10.1016/j.xcrm.2024.101753","DOIUrl":"10.1016/j.xcrm.2024.101753","url":null,"abstract":"Radiotherapy resistance is the main cause of treatment failure among patients with nasopharyngeal carcinoma (NPC). Recently, increasing evidence has linked the presence of intratumoral Fusobacterium nucleatum (Fn) with the malignant progression and therapeutic resistance of multiple tumor types, but its influence on NPC has remained largely unknown. We found that Fn is prevalent in the tumor tissue of patients with NPC and is associated with radioresistance. Fn invaded and proliferated inside NPC cells and aggravated tumor progression. Mechanistically, Fn slowed mitochondrial dysfunction by promoting mitochondrial fusion and decreasing ROS generation, preventing radiation-induced oxidative damage. Fn inhibited PANoptosis by the SLC7A5/leucine-mTORC1 axis during irradiation stress, thus promoting radioresistance. Treatment with the mitochondria-targeted antibiotics or dietary restriction of leucine reduced intratumoral Fn load, resensitizing tumors to radiotherapy in vivo. These findings demonstrate that Fn has the potential to be a predictive marker for radioresistance and to help guide individualized treatment for patients with NPC.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activated sympathetic nerve post stroke downregulates Toll-like receptor 5 and disrupts the gut mucosal barrier. 中风后激活的交感神经会下调 Toll 样受体 5，破坏肠道粘膜屏障。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 Epub Date: 2024-10-08 DOI: 10.1016/j.xcrm.2024.101754

Huidi Wang, Jie Li, Guangyan Wu, Xiaofei Lin, Jiaying Chen, Jingru Liang, Jiahui Zhang, Xiaoxia Luo, Hongyun Mao, Jiahui Xie, Zhuang Li, Hongwei Zhou, Kaiyu Xu, Jia Yin, Yan He

{"title":"Activated sympathetic nerve post stroke downregulates Toll-like receptor 5 and disrupts the gut mucosal barrier.","authors":"Huidi Wang, Jie Li, Guangyan Wu, Xiaofei Lin, Jiaying Chen, Jingru Liang, Jiahui Zhang, Xiaoxia Luo, Hongyun Mao, Jiahui Xie, Zhuang Li, Hongwei Zhou, Kaiyu Xu, Jia Yin, Yan He","doi":"10.1016/j.xcrm.2024.101754","DOIUrl":"10.1016/j.xcrm.2024.101754","url":null,"abstract":"The gut permeability significantly increases after ischemic stroke, partly due to disrupted mucosal barrier, but the mechanism remains elusive. Here, we found that the mucus disruption starts at 2 h post stroke, whereas goblet cell functions remain intact. Meanwhile, the flagellated bacteria Helicobacter thrives and penetrates in the mucus layer. Elimination of the mucosal microbiota or transplantation of Helicobacter in germ-free mice reveals an important role of the mucosal microbiota in mucus disruption. The bacterial invasion is due to downregulated Toll-like receptor 5 (TLR5) and its downstream products flagellin-specific IgA and antimicrobial peptides. Knockdown of intestinal TLR5 increases the abundance of flagellated bacteria and exacerbates mucus injury. Intestinal TLR5 is downregulated by the activation of sympathetic nerve. Serum noradrenaline level is positively associated with flagellin level in patients with stroke and patients' prognosis. These findings reveal a neural pathway in which the sympathetic nerve disrupts the mucosal barrier, providing potential therapeutic targets for stroke injury.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mast cell modulation: A novel therapeutic strategy for abdominal pain in irritable bowel syndrome. 调节肥大细胞：肠易激综合征腹痛的新型治疗策略。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 Epub Date: 2024-10-07 DOI: 10.1016/j.xcrm.2024.101780

Samuel Van Remoortel, Hind Hussein, Guy Boeckxstaens

引用次数: 0

Single-cell profiling reveals a conserved role for hypoxia-inducible factor signaling during human craniotomy infection. 单细胞图谱分析揭示了缺氧诱导因子信号在人类开颅手术感染过程中的保守作用。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 DOI: 10.1016/j.xcrm.2024.101790

Zachary Van Roy, Gunjan Kak, Lee E Korshoj, Joseph P Menousek, Cortney E Heim, Rachel W Fallet, James R Campbell, Carol R Geary, Bo Liu, Santhi Gorantla, Larisa Y Poluektova, Bin Duan, W Scott Campbell, William E Thorell, Tammy Kielian

{"title":"Single-cell profiling reveals a conserved role for hypoxia-inducible factor signaling during human craniotomy infection.","authors":"Zachary Van Roy, Gunjan Kak, Lee E Korshoj, Joseph P Menousek, Cortney E Heim, Rachel W Fallet, James R Campbell, Carol R Geary, Bo Liu, Santhi Gorantla, Larisa Y Poluektova, Bin Duan, W Scott Campbell, William E Thorell, Tammy Kielian","doi":"10.1016/j.xcrm.2024.101790","DOIUrl":"https://doi.org/10.1016/j.xcrm.2024.101790","url":null,"abstract":"Neurosurgeries complicated by infection are associated with prolonged treatment and significant morbidity. Craniotomy is a common neurosurgical procedure; however, the cellular and molecular signatures associated with craniotomy infection in human subjects are unknown. A retrospective study of over 2,500 craniotomies reveals diverse patient demographics, pathogen identity, and surgical landscapes associated with infection. Leukocyte profiling in patient tissues from craniotomy infection characterizes a predominance of granulocytic myeloid-derived suppressor cells that may arise from transmigrated blood neutrophils, based on single-cell RNA sequencing (scRNA-seq) trajectory analysis. Single-cell transcriptomic analysis identifies metabolic shifts in tissue leukocytes, including a conserved hypoxia-inducible factor (HIF) signature. The importance of HIF signaling was validated using a mouse model of Staphylococcus aureus craniotomy infection, where HIF inhibition increases chemokine production and leukocyte recruitment, exacerbating tissue pathology. These findings establish conserved metabolic and transcriptional signatures that may represent promising future therapeutic targets for human craniotomy infection in the face of increasing antimicrobial resistance.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity. Denosumab能刺激保留了Sertoli细胞能力的不育男性的精子生成。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 Epub Date: 2024-10-08 DOI: 10.1016/j.xcrm.2024.101783

Christine H Andreassen, Rune Holt, Li Juel Mortensen, Nadia Krarup Knudsen, John E Nielsen, Nadia Nicholine Poulsen, Sam K Yahyavi, Ida M Boisen, Zhihui Cui, Luisina Ongaro, Jasmin P Hjerresen, Birgitte G Toft, Thomas Hasselager, Niklas R Jørgensen, Daniel J Bernard, Anders Juul, Charles O'Brien, Anne Jørgensen, Martin Blomberg Jensen

{"title":"Denosumab stimulates spermatogenesis in infertile men with preserved Sertoli cell capacity.","authors":"Christine H Andreassen, Rune Holt, Li Juel Mortensen, Nadia Krarup Knudsen, John E Nielsen, Nadia Nicholine Poulsen, Sam K Yahyavi, Ida M Boisen, Zhihui Cui, Luisina Ongaro, Jasmin P Hjerresen, Birgitte G Toft, Thomas Hasselager, Niklas R Jørgensen, Daniel J Bernard, Anders Juul, Charles O'Brien, Anne Jørgensen, Martin Blomberg Jensen","doi":"10.1016/j.xcrm.2024.101783","DOIUrl":"10.1016/j.xcrm.2024.101783","url":null,"abstract":"Sperm production depends on proper Sertoli-germ cell interaction, and we hypothesized that receptor activator of nuclear factor κB ligand (RANKL) activity in Sertoli cells may influence spermatogenesis. Treatment with the RANKL inhibitor denosumab, normally used to treat osteoporosis, increased testicular weight, inhibin B, and germ cell proliferation in ex vivo testis cultures and in vivo in a humanized RANKL mouse. The effect on germ cell proliferation was positively associated with baseline serum concentrations of anti-müllerian hormone (AMH). In accordance, denosumab increased germ cell proliferation in ex vivo human testis cultures with low/moderate but not severe impairment of Sertoli cell function. In a placebo-controlled randomized clinical trial, denosumab had no effect on semen quality but increased sperm concentration in a subgroup of infertile men with serum AMH ≥38 pmol/L at baseline. In conclusion, high serum AMH may increase the probability of a beneficial response to denosumab treatment in infertile men, thus suggesting a possible venue for precision medicine in male infertility.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep learning model with pathological knowledge for detection of colorectal neuroendocrine tumor. 利用病理学知识检测结直肠神经内分泌肿瘤的深度学习模型。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 DOI: 10.1016/j.xcrm.2024.101785

Ke Zheng, Jinling Duan, Ruixuan Wang, Haohua Chen, Haiyang He, Xueyi Zheng, Zihan Zhao, Bingzhong Jing, Yuqian Zhang, Shasha Liu, Dan Xie, Yuan Lin, Yan Sun, Ning Zhang, Muyan Cai

{"title":"Deep learning model with pathological knowledge for detection of colorectal neuroendocrine tumor.","authors":"Ke Zheng, Jinling Duan, Ruixuan Wang, Haohua Chen, Haiyang He, Xueyi Zheng, Zihan Zhao, Bingzhong Jing, Yuqian Zhang, Shasha Liu, Dan Xie, Yuan Lin, Yan Sun, Ning Zhang, Muyan Cai","doi":"10.1016/j.xcrm.2024.101785","DOIUrl":"10.1016/j.xcrm.2024.101785","url":null,"abstract":"Colorectal neuroendocrine tumors (NETs) differ significantly from colorectal carcinoma (CRC) in terms of treatment strategy and prognosis, necessitating a cost-effective approach for accurate discrimination. Here, we propose an approach for distinguishing between colorectal NET and CRC based on pathological images by utilizing pathological prior information to facilitate the generation of robust slide-level features. By calculating the similarity between morphological descriptions and patches, our approach selects only 2% of the diagnostically relevant patches for both training and inference, achieving an area under the receiver operating characteristic curve (AUROC) of 0.9974 on the internal dataset, and AUROCs of 0.9724 and 0.9513 on two external datasets. Our model effectively identifies NETs from CRCs, reducing unnecessary immunohistochemical tests and enhancing the precise treatment for patients with colorectal tumors. Our approach also enables researchers to investigate methods with high accuracy and low computational complexity, thereby advancing the application of artificial intelligence in clinical settings.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CDK12 loss drives prostate cancer progression, transcription-replication conflicts, and synthetic lethality with paralog CDK13. CDK12 的缺失会导致前列腺癌进展、转录-复制冲突以及与同系物 CDK13 的合成致死。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 Epub Date: 2024-10-04 DOI: 10.1016/j.xcrm.2024.101758

Jean Ching-Yi Tien, Jie Luo, Yu Chang, Yuping Zhang, Yunhui Cheng, Xiaoju Wang, Jianzhang Yang, Rahul Mannan, Somnath Mahapatra, Palak Shah, Xiao-Ming Wang, Abigail J Todd, Sanjana Eyunni, Caleb Cheng, Ryan J Rebernick, Lanbo Xiao, Yi Bao, James Neiswender, Rachel Brough, Stephen J Pettitt, Xuhong Cao, Stephanie J Miner, Licheng Zhou, Yi-Mi Wu, Estefania Labanca, Yuzhuo Wang, Abhijit Parolia, Marcin Cieslik, Dan R Robinson, Zhen Wang, Felix Y Feng, Jonathan Chou, Christopher J Lord, Ke Ding, Arul M Chinnaiyan

{"title":"CDK12 loss drives prostate cancer progression, transcription-replication conflicts, and synthetic lethality with paralog CDK13.","authors":"Jean Ching-Yi Tien, Jie Luo, Yu Chang, Yuping Zhang, Yunhui Cheng, Xiaoju Wang, Jianzhang Yang, Rahul Mannan, Somnath Mahapatra, Palak Shah, Xiao-Ming Wang, Abigail J Todd, Sanjana Eyunni, Caleb Cheng, Ryan J Rebernick, Lanbo Xiao, Yi Bao, James Neiswender, Rachel Brough, Stephen J Pettitt, Xuhong Cao, Stephanie J Miner, Licheng Zhou, Yi-Mi Wu, Estefania Labanca, Yuzhuo Wang, Abhijit Parolia, Marcin Cieslik, Dan R Robinson, Zhen Wang, Felix Y Feng, Jonathan Chou, Christopher J Lord, Ke Ding, Arul M Chinnaiyan","doi":"10.1016/j.xcrm.2024.101758","DOIUrl":"10.1016/j.xcrm.2024.101758","url":null,"abstract":"Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a metastatic castration-resistant prostate cancer (mCRPC) subtype. It remains unclear, however, whether CDK12 loss drives prostate cancer (PCa) development or uncovers pharmacologic vulnerabilities. Here, we show Cdk12 ablation in murine prostate epithelium is sufficient to induce preneoplastic lesions with lymphocytic infiltration. In allograft-based CRISPR screening, Cdk12 loss associates positively with Trp53 inactivation but negatively with Pten inactivation. Moreover, concurrent Cdk12/Trp53 ablation promotes proliferation of prostate-derived organoids, while Cdk12 knockout in Pten-null mice abrogates prostate tumor growth. In syngeneic systems, Cdk12/Trp53-null allografts exhibit luminal morphology and immune checkpoint blockade sensitivity. Mechanistically, Cdk12 inactivation mediates genomic instability by inducing transcription-replication conflicts. Strikingly, CDK12-mutant organoids and patient-derived xenografts are sensitive to inhibition or degradation of the paralog kinase, CDK13. We therein establish CDK12 as a bona fide tumor suppressor, mechanistically define how CDK12 inactivation causes genomic instability, and advance a therapeutic strategy for CDK12-mutant mCRPC.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pig-to-human kidney xenotransplants using genetically modified minipigs. 利用转基因小猪进行猪-人肾脏异种移植。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 Epub Date: 2024-09-23 DOI: 10.1016/j.xcrm.2024.101744

Yi Wang, Gang Chen, Dengke Pan, Hui Guo, Hongtao Jiang, Jianli Wang, Hao Feng, Songzhe He, Jiaxiang Du, Man Zhang, Tao Li, Yong Wang, Hang Yu, Huiling Gan, Quan Wen, Zhian Song, Desheng Li, Yifan Yu, Huanliang Wang, Bing Li, Yong You, Shen Zhou, Mingfa Wang, Lili Liu, Liang Xu, Meng Yang, Hua Pei, Kang Zhang, Zhonghua K Chen

{"title":"Pig-to-human kidney xenotransplants using genetically modified minipigs.","authors":"Yi Wang, Gang Chen, Dengke Pan, Hui Guo, Hongtao Jiang, Jianli Wang, Hao Feng, Songzhe He, Jiaxiang Du, Man Zhang, Tao Li, Yong Wang, Hang Yu, Huiling Gan, Quan Wen, Zhian Song, Desheng Li, Yifan Yu, Huanliang Wang, Bing Li, Yong You, Shen Zhou, Mingfa Wang, Lili Liu, Liang Xu, Meng Yang, Hua Pei, Kang Zhang, Zhonghua K Chen","doi":"10.1016/j.xcrm.2024.101744","DOIUrl":"10.1016/j.xcrm.2024.101744","url":null,"abstract":"This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, β4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The μ-opioid receptor differentiates two distinct human nociceptive populations relevant to clinical pain. μ-阿片受体可区分与临床疼痛相关的两种不同的人类痛觉群体。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 DOI: 10.1016/j.xcrm.2024.101788

Ellen S Staedtler, Matthew R Sapio, Diana M King, Dragan Maric, Andre Ghetti, Andrew J Mannes, Michael J Iadarola

{"title":"The μ-opioid receptor differentiates two distinct human nociceptive populations relevant to clinical pain.","authors":"Ellen S Staedtler, Matthew R Sapio, Diana M King, Dragan Maric, Andre Ghetti, Andrew J Mannes, Michael J Iadarola","doi":"10.1016/j.xcrm.2024.101788","DOIUrl":"10.1016/j.xcrm.2024.101788","url":null,"abstract":"The shortfall in new analgesic agents is a major impediment to reducing reliance on opioid medications for control of severe pain. In both animals and man, attenuating nociceptive transmission from primary afferent neurons with a μ-opioid receptor agonist yields highly effective analgesia. Consequently, deeper molecular characterization of human nociceptive afferents expressing OPRM1, the μ-opioid receptor gene, is a key component for advancing analgesic drug discovery and understanding clinical pain control. A co-expression matrix for the μ-opioid receptor and a variety of nociceptive channels as well as δ- and κ-opioid receptors is established by multiplex in situ hybridization. Our results indicate an OPRM1-positive population with strong molecular resemblance to rodent peptidergic C-nociceptors associated with tissue damage pain and an OPRM1-negative population sharing molecular characteristics of murine non-peptidergic C-nociceptors. The empirical identification of two distinct human nociceptive populations that differ profoundly in their presumed responsiveness to opioids provides an actionable translational framework for human pain control.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combinatorial leaky probiotic for anticancer immunopotentiation and tumor eradication. 用于抗癌免疫增强和肿瘤根除的组合型渗漏性益生菌。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-10-15 DOI: 10.1016/j.xcrm.2024.101793

Cheng-Hao Liu, Yi-Chung Pan, See-Khai Lim, Chung-Yuan Mou, Che-Ming Jack Hu, Kurt Yun Mou

{"title":"Combinatorial leaky probiotic for anticancer immunopotentiation and tumor eradication.","authors":"Cheng-Hao Liu, Yi-Chung Pan, See-Khai Lim, Chung-Yuan Mou, Che-Ming Jack Hu, Kurt Yun Mou","doi":"10.1016/j.xcrm.2024.101793","DOIUrl":"https://doi.org/10.1016/j.xcrm.2024.101793","url":null,"abstract":"Combination therapies present a compelling therapeutic regimen against the immunosuppressive and heterogeneous microenvironment of solid tumors. However, incorporating separate therapeutic modalities in regimen designs can be encumbered by complex logistical, manufacturing, and pharmacokinetic considerations. Herein, we demonstrate a single-vector combinational anticancer therapy using an lpp gene knockout leaky probiotic for simultaneous secretion of immunotherapeutic and oncolytic effector molecules. Through fusion protein design and vector optimization, a Nissle1917 (EcN) bacteria vector is engineered to secrete Neoleukin-2/15 (Neo-2/15) cytokine-functionalized anti-PDL1 nanobody (aPDL1-Neo2/15) and anti-mesothelin-functionalized hemolysin E (HlyE-aMSLN). The multifunctional leaky probiotic enables synchronous immune activation and tumor-targeted cytolytic activity for effective tumor suppression, elevation of tumor immune cell infiltration, and establishment of anticancer immunological memory. lpp gene knockout is further shown to improve probiotic tolerability and intravenous applicability, offering a therapeutically viable approach for combination regimen development.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0