Clinical translation of a novel FAPI dimer [ < sup > 68 < /sup > Ga]Ga-LNC1013
CONCLUSION: Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over its monomeric counterpart. We demonstrated that [68Ga]Ga-LNC1013, the lead compound without any piperazine moiety, had superior diagnostic potential over [68Ga]Ga-FAPI-46 and 18F-FDG, suggesting the future potential of LNC1013 for radioligand therapy of FAP-positive cancers.PMID:38561515 | DOI:10.1007/s00259-024-06703-z (Source: Molecular Medicine)
Source: Molecular Medicine - April 1, 2024 Category: Molecular Biology Authors: Yue Tan Jian Li Tianzhi Zhao Ming Zhou Kehuang Liu Shijun Xiang Yongxiang Tang Vivianne Jakobsson Pengfei Xu Xiaoyuan Chen Jingjing Zhang Source Type: research
Disrupted gut microecology after high-dose < sup > 131 < /sup > I therapy and radioprotective effects of arachidonic acid supplementation
CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.PMID:38561516 | DOI:10.1007/s00259-024-06688-9 (Source: Molecular Medicine)
Source: Molecular Medicine - April 1, 2024 Category: Molecular Biology Authors: Ganghua Lu Dingwei Gao Wen Jiang Xiaqing Yu Junyu Tong Xiaoyan Liu Tingting Qiao Ru Wang Mengyu Zhang Shaoping Wang Jianshe Yang Dan Li Zhongwei Lv Source Type: research
CRISPR/Cas9n-mediated ELANE promoter editing for gene therapy of severe congenital neutropenia
Mol Ther. 2024 Mar 30:S1525-0016(24)00215-6. doi: 10.1016/j.ymthe.2024.03.037. Online ahead of print.ABSTRACTSevere congenital neutropenia (CN) is an inherited pre-leukemia bone marrow failure syndrome commonly caused by autosomal-dominant ELANE mutations (ELANE-CN). ELANE-CN patients are treated with daily injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF). However, some patients do not respond to rhG-CSF, and approximately 15% of ELANE-CN patients develop myelodysplasia or acute myeloid leukemia. Here, we report the development of a curative therapy for ELANE-CN through inhibition of ELANE mR...
Source: Molecular Medicine - April 1, 2024 Category: Molecular Biology Authors: Masoud Nasri Malte Ritter Perihan Mir Benjamin Dannenmann Masako M Kaufmann Patricia Arreba-Tutusaus Yun Xu Natalia Borbaran-Bravo Maksim Klimiankou Claudia Lengerke Cornelia Zeidler Toni Cathomen Karl Welte Julia Skokowa Source Type: research
DNA methylation in necrotizing enterocolitis
Expert Rev Mol Med. 2024 Apr 1:1-20. doi: 10.1017/erm.2024.16. Online ahead of print.NO ABSTRACTPMID:38557638 | DOI:10.1017/erm.2024.16 (Source: Molecular Medicine)
Source: Molecular Medicine - April 1, 2024 Category: Molecular Biology Authors: Lauren C Frazer Yukihiro Yamaguchi Dhirendra K Singh Natalia S Akopyants Misty Good Source Type: research
The status of nuclear medicine in China: the first official national survey
CONCLUSION: These results of the first official survey towards current status of nuclear medicine in China are the foundation for the establishment of the quality control management system.PMID:38561514 | DOI:10.1007/s00259-024-06687-w (Source: Molecular Medicine)
Source: Molecular Medicine - April 1, 2024 Category: Molecular Biology Authors: Haiqiong Zhang Jin Zheng Nan Hu Yu Liu Guangjie Yang Meixi Liu Hongli Jing Li Huo Source Type: research
Clinical translation of a novel FAPI dimer [ < sup > 68 < /sup > Ga]Ga-LNC1013
CONCLUSION: Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over its monomeric counterpart. We demonstrated that [68Ga]Ga-LNC1013, the lead compound without any piperazine moiety, had superior diagnostic potential over [68Ga]Ga-FAPI-46 and 18F-FDG, suggesting the future potential of LNC1013 for radioligand therapy of FAP-positive cancers.PMID:38561515 | DOI:10.1007/s00259-024-06703-z (Source: Molecular Medicine)
Source: Molecular Medicine - April 1, 2024 Category: Molecular Biology Authors: Yue Tan Jian Li Tianzhi Zhao Ming Zhou Kehuang Liu Shijun Xiang Yongxiang Tang Vivianne Jakobsson Pengfei Xu Xiaoyuan Chen Jingjing Zhang Source Type: research
Disrupted gut microecology after high-dose < sup > 131 < /sup > I therapy and radioprotective effects of arachidonic acid supplementation
CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.PMID:38561516 | DOI:10.1007/s00259-024-06688-9 (Source: Molecular Medicine)
Source: Molecular Medicine - April 1, 2024 Category: Molecular Biology Authors: Ganghua Lu Dingwei Gao Wen Jiang Xiaqing Yu Junyu Tong Xiaoyan Liu Tingting Qiao Ru Wang Mengyu Zhang Shaoping Wang Jianshe Yang Dan Li Zhongwei Lv Source Type: research
Age-dependent loss of Crls1 causes myopathy and skeletal muscle regeneration failure
This study investigated the crucial role of mitochondrial cardiolipin and cardiolipin synthase 1 (Crls1) in age-related muscle deterioration and myogenesis. Our findings demonstrated that cardiolipin and Crls1 are downregulated in aged skeletal muscle. Moreover, the knockdown of Crls1 in myoblasts reduced mitochondrial mass, activity, and OXPHOS complex IV expression and disrupted the structure of the mitochondrial cristae. AAV9-shCrls1-mediated downregulation of Crls1 impaired muscle regeneration in a mouse model of cardiotoxin (CTX)-induced muscle damage, whereas AAV9-mCrls1-mediated Crls1 overexpression improved regener...
Source: Molecular Medicine - March 31, 2024 Category: Molecular Biology Authors: Youngbum Yoo MyeongHoon Yeon Won-Kyung Kim Hyeon-Bin Shin Seung-Min Lee Mee-Sup Yoon Hyunju Ro Young-Kyo Seo Source Type: research
Recent advances in extracellular vesicles for therapeutic cargo delivery
Exp Mol Med. 2024 Apr 1. doi: 10.1038/s12276-024-01201-6. Online ahead of print.ABSTRACTExosomes, which are nanosized vesicles secreted by cells, are attracting increasing interest in the field of biomedical research due to their unique properties, including biocompatibility, cargo loading capacity, and deep tissue penetration. They serve as natural signaling agents in intercellular communication, and their inherent ability to carry proteins, lipids, and nucleic acids endows them with remarkable therapeutic potential. Thus, exosomes can be exploited for diverse therapeutic applications, including chemotherapy, gene therapy...
Source: Molecular Medicine - March 31, 2024 Category: Molecular Biology Authors: Hyo In Kim Jinbong Park Yin Zhu Xiaoyun Wang Yohan Han Duo Zhang Source Type: research
Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2
Exp Mol Med. 2024 Apr 1. doi: 10.1038/s12276-024-01203-4. Online ahead of print.ABSTRACTAcute liver injury is the basis of the pathogenesis of diverse liver diseases. However, the mechanism underlying liver injury is complex and not completely understood. In our study, we revealed that CERK, which phosphorylates ceramide to produce ceramide-1-phosphate (C1P), was the sphingolipid pathway-related protein that had the most significantly upregulated expression during acute liver injury. A functional study confirmed that CERK and C1P attenuate hepatic injury both in vitro and in vivo through antioxidant effects. Mechanistic st...
Source: Molecular Medicine - March 31, 2024 Category: Molecular Biology Authors: Wei Dong Qing Li Xing Lu Jianfeng Lan Zhidong Qiu Xuehong Wang Junnan Wang Xiaojiao Zheng Sifan Chen Chong Zhang Junfei Jin Source Type: research
Experimental capture of miRNA targetomes: disease-specific 3'UTR library-based miRNA targetomics for Parkinson's disease
Exp Mol Med. 2024 Apr 1. doi: 10.1038/s12276-024-01202-5. Online ahead of print.ABSTRACTThe identification of targetomes remains a challenge given the pleiotropic effect of miRNAs, the limited effects of miRNAs on individual targets, and the sheer number of estimated miRNA-target gene interactions (MTIs), which is around 44,571,700. Currently, targetome identification for single miRNAs relies on computational evidence and functional studies covering smaller numbers of targets. To ensure that the targetome analysis could be experimentally verified by functional assays, we employed a systematic approach and explored the targ...
Source: Molecular Medicine - March 31, 2024 Category: Molecular Biology Authors: Martin Hart Fabian Kern Claudia Fecher-Trost Lena Krammes Ernesto Aparicio Annika Engel Pascal Hirsch Viktoria Wagner Verena Keller Georges Pierre Schmartz Stefanie Rheinheimer Caroline Diener Ulrike Fischer Jens Mayer Markus R Meyer Veit Flockerzi Andrea Source Type: research
Transcriptome-based deep learning analysis identifies drug candidates targeting protein synthesis and autophagy for the treatment of muscle wasting disorder
This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved mu...
Source: Molecular Medicine - March 31, 2024 Category: Molecular Biology Authors: Min Hak Lee Bada Lee Se Eun Park Ga Eul Yang Seungwoo Cheon Dae Hoon Lee Sukyeong Kang Ye Ji Sun Yongjin Kim Dong-Sub Jung Wonwoo Kim Jihoon Kang Yi Rang Kim Jin Woo Choi Source Type: research
Methyl-CpG binding domain protein 2 (Mbd2) drives breast cancer progression through the modulation of epithelial-to-mesenchymal transition
Exp Mol Med. 2024 Apr 1. doi: 10.1038/s12276-024-01205-2. Online ahead of print.ABSTRACTMethyl-CpG-binding domain protein 2 (Mbd2), a reader of DNA methylation, has been implicated in different types of malignancies, including breast cancer. However, the exact role of Mbd2 in various stages of breast cancer growth and progression in vivo has not been determined. To test whether Mbd2 plays a causal role in mammary tumor growth and metastasis, we performed genetic knockout (KO) of Mbd2 in MMTV-PyMT transgenic mice and compared mammary tumor progression kinetics between the wild-type (PyMT-Mbd2+/+) and KO (PyMT-Mbd2-/-) group...
Source: Molecular Medicine - March 31, 2024 Category: Molecular Biology Authors: Niaz Mahmood Ani Arakelian Moshe Szyf Shafaat A Rabbani Source Type: research
Recent advances in CRISPR-based functional genomics for the study of disease-associated genetic variants
Exp Mol Med. 2024 Apr 1. doi: 10.1038/s12276-024-01212-3. Online ahead of print.ABSTRACTAdvances in sequencing technology have greatly increased our ability to gather genomic data, yet understanding the impact of genetic mutations, particularly variants of uncertain significance (VUSs), remains a challenge in precision medicine. The CRISPR‒Cas system has emerged as a pivotal tool for genome engineering, enabling the precise incorporation of specific genetic variations, including VUSs, into DNA to facilitate their functional characterization. Additionally, the integration of CRISPR‒Cas technology with sequencing tools a...
Source: Molecular Medicine - March 31, 2024 Category: Molecular Biology Authors: Heon Seok Kim Jiyeon Kweon Yongsub Kim Source Type: research
Cargo specificity, regulation, and therapeutic potential of cytoplasmic dynein
Exp Mol Med. 2024 Apr 1. doi: 10.1038/s12276-024-01200-7. Online ahead of print.ABSTRACTIntracellular retrograde transport in eukaryotic cells relies exclusively on the molecular motor cytoplasmic dynein 1. Unlike its counterpart, kinesin, dynein has a single isoform, which raises questions about its cargo specificity and regulatory mechanisms. The precision of dynein-mediated cargo transport is governed by a multitude of factors, including temperature, phosphorylation, the microtubule track, and interactions with a family of activating adaptor proteins. Activating adaptors are of particular importance because they not onl...
Source: Molecular Medicine - March 31, 2024 Category: Molecular Biology Authors: Jin-Gyeong Park Hanul Jeon Kwang Yeon Hwang Sun-Shin Cha Rafael T Han Hyesung Cho In-Gyun Lee Source Type: research
