Article
Gastroenterology & Hepatology
Allyson J. Merrell, Tao Peng, Jinyang Li, Kathryn Sun, Bin Li, Takeshi Katsuda, Markus Grompe, Kai Tan, Ben Z. Stanger
Summary: Hepatocytes undergo extensive chromatin and transcriptional changes during biliary reprogramming, resulting in altered gene expression profiles including robust induction of biliary genes and weaker repression of hepatocyte genes. Single-cell analysis revealed that Smad4 mutation can significantly increase reprogramming.
Article
Medicine, Research & Experimental
Hongmei Zhao, Hongqin Yang, Chi Geng, Yang Chen, Yaqin Tang, Zhiwei Li, Junling Pang, Ting Shu, Yu Nie, Yongshuo Liu, Kegang Jia, Jing Wang
Summary: Research shows that elevated IgE promotes pathological cardiac fibrosis by modulating miR-486a-5p and downstream factors, such as Smad1, providing new targets for intervention in pathological cardiac fibrosis.
Article
Cardiac & Cardiovascular Systems
Quan Liu, Hua-Yang Li, Shun-Jun Wang, Sui-Qing Huang, Yuan Yue, Adilai Maihemuti, Yi Zhang, Lin Huang, Li Luo, Kang-Ni Feng, Zhong-Kai Wu
Summary: The ROCK2-specific inhibitor, belumosudil, effectively alleviates cardiac hypertrophy, fibrosis, and dysfunction induced by TAC through inhibiting cardiac fibroblast activation. The mechanism underlying cardiac fibrosis involves the interaction of ROCK2 with the TGF-β1/Smad2 pathway.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ming-an Sun, Gernot Wolf, Yejun Wang, Anna D. Senft, Sherry Ralls, Jinpu Jin, Caitlin E. Dunn-Fletcher, Louis J. Muglia, Todd S. Macfarlan
Summary: The study identified numerous lineage-specific gene expression in different mammalian placentae, shedding light on the evolutionary process of placenta. The overlap between specific families of endogenous retroviruses and lineage-specific placental enhancers likely facilitates the lineage-specific evolution of the mammalian placenta.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Cardiac & Cardiovascular Systems
Tatsuya Aonuma, Bruno Moukette, Satoshi Kawaguchi, Nipuni P. Barupala, Marisa N. Sepulveda, Kyle Frick, Yaoliang Tang, Maya Guglin, Subha Raman, Chenleng Cai, Suthat Liangpunsakul, Shinichi Nakagawa, Il-man Kim
Summary: In this study, the functional interaction among MIAT, miR-150, and Hoxa4 in ischemic heart failure was investigated. The findings provide valuable insights into the regulatory mechanism of these noncoding RNAs in cardiac protection.
CIRCULATION-HEART FAILURE
(2022)
Article
Cell Biology
Hanane Akboua, Kaveh Eghbalzadeh, Ugur Keser, Thorsten Wahlers, Adnana Paunel-Gorgulu
Summary: The activation of TGF-beta in the infarcted heart can lead to adverse cardiac remodeling and heart failure by persistently activating cardiac fibroblasts. PAD4 plays a role in regulating non-canonical TGF-beta signaling, affecting the functional characteristics of CFs and myofibroblast transdifferentiation.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Astronomy & Astrophysics
S. Spezzano, O. Sipilae, P. Caselli, S. S. Jensen, S. Czakli, L. Bizzocchi, J. Chantzos, G. Esplugues, A. Fuente, F. Eisenhauer
Summary: Deuteration plays a crucial role in understanding the interstellar chemical processes, and this study focuses on the D/H ratio in H2CS across the L1544 prototypical pre-stellar core. The results show that the maximum deuterium fractionation for the first deuteration of H2CS is around 30% and is located at a distance of about 10,000 AU from the dust peak. The second deuteration of H2CS and H2CO is more efficient, leading to a higher deuterium fractionation. The large deuteration of H2CO and H2CS observed in protostellar cores and comets is likely inherited from the pre-stellar phase. However, the reaction network for the formation of doubly deuterated H2CS and H2CO is not yet complete according to the comparison with state-of-the-art chemical models.
ASTRONOMY & ASTROPHYSICS
(2022)
Article
Plant Sciences
Meizhong Peng, Meiling Yang, Yan Lu, Shan Lin, Huajian Gao, Lingling Xie, Bin Huang, Daxin Chen, Aling Shen, Zhiqing Shen, Jun Peng, Jianfeng Chu
Summary: Huoxin Pill (HXP) can suppress ISO-induced cardiac fibrosis and CFs transdifferentiation by inhibiting the activation of the TGF-beta/Smads pathway, potentially serving as a new therapeutic tool for cardiac fibrosis.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Cell Biology
Wuming Gong, Satyabrata Das, Javier E. Sierra-Pagan, Erik Skie, Nikita Dsouza, Thijs A. Larson, Mary G. Garry, Edgar Luzete-Monteiro, Kenneth S. Zaret, Daniel J. Garry
Summary: Gong et al. report that ETV2 functions as a pioneer factor in regulating endothelial genes and remodeling chromatin, which provides potential therapeutic applications for cardiovascular diseases and solid tumors.
NATURE CELL BIOLOGY
(2022)
Article
Cell Biology
Glynnis A. Garry, Svetlana Bezprozvannaya, Kenian Chen, Huanyu Zhou, Hisayuki Hashimoto, Maria Gabriela Morales, Ning Liu, Rhonda Bassel-Duby, Eric N. Olson
Summary: The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super enhancers to increase accessibility to core cardiac transcription factors, facilitating direct cardiac reprogramming.
NATURE CELL BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Yawen Tang, Sajesan Aryal, Xiaoxiao Geng, Xinyue Zhou, Vladimir G. Fast, Jianyi Zhang, Rui Lu, Yang Zhou
Summary: The addition of TBX20 to the MGT133 reprogramming cocktail promotes cardiac reprogramming and enhances cardiac function in induced cardiomyocytes by activating genes associated with cardiac contractility and mitochondrial respiration.
Article
Cell Biology
Peter-Paul A. Unger, Niels J. M. Verstegen, Casper Marsman, Tineke Jorritsma, Theo Rispens, Anja ten Brinke, S. Marieke van Ham
Summary: Efficient differentiation of human naive B cells into antibody-secreting cells can be achieved by controlling the interaction between CD40 costimulation and Tfh cell-associated cytokines IL-21 and IL-4 in an in vitro culture system. Renewed CD40 costimulation in vitro can induce rapid terminal ASC differentiation after initial B-cell expansion, similar to the process in vivo.
Article
Nanoscience & Nanotechnology
Letizia Nicoletti, Camilla Paoletti, Giulia Tarricone, Ilaria Andreana, Barbara Stella, Silvia Arpicco, Carla Divieto, Clara Mattu, Valeria Chiono
Summary: Designing nanocarriers for efficient miRNA delivery is crucial for improving miRNA-based therapies. In this study, DE-DOPE/miRNA lipoplexes were formulated and showed superior stability, loading efficiency, and release speed compared to commercial Dharma FECT1 (DF). The DE-DOPE/miRNA lipoplexes demonstrated high viability and gene regulation ability in cardiac fibroblasts, highlighting their potential for enhancing miRNA-based therapies.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Article
Multidisciplinary Sciences
Carlos Bueno, Marta Martinez-Morga, David Garcia-Bernal, Jose M. Moraleda, Salvador Martinez
Summary: Stem cells isolated from adult tissues can directly differentiate into neuron-like cells without passing through a mitotic stage. The morphological change is achieved through active neurite extension rather than cytoplasm retraction. Movement of micronuclei and transient cell nuclei lobulation were observed during in vitro neurogenesis from bone marrow-derived and dental pulp-derived stem cells.
SCIENTIFIC REPORTS
(2021)
Review
Immunology
Camille A. Spinner, Vanja Lazarevic
Summary: CD4(+) T cells differentiate into distinct T helper subsets under the control of specific transcription factors after encountering antigens. These transcription factors interact with each other to orchestrate cell lineage specification programs. Additionally, they play critical roles in controlling T cell development in the thymus and innate lymphoid cell development in the bone marrow.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Multidisciplinary Sciences
Yanxiang Deng, Marek Bartosovic, Sai Ma, Di Zhang, Petra Kukanja, Yang Xiao, Graham Su, Yang Liu, Xiaoyu Qin, Gorazd B. Rosoklija, Andrew J. Dwork, J. John Mann, Mina L. Xu, Stephanie Halene, Joseph E. Craft, Kam W. Leong, Maura Boldrini, Goncalo Castelo-Branco, Rong Fan
Summary: This study presents a new method for spatial chromatin accessibility profiling in tissues, allowing researchers to explore the spatial epigenetic information at the cellular level and genome scale. The technology has been successfully applied to understand gene regulators in the development of the central nervous system and immune cell types in tonsil tissue. This advancement in spatial biology improves our understanding of cell identity, cell state, and cell fate decision in relation to epigenetic underpinnings in development and disease.
Review
Multidisciplinary Sciences
Letao Yang, Lin Y. Hung, Yuefei Zhu, Suwan Ding, Kara G. Margolis, Kam W. Leong
Summary: “The Role of Gut Microbiome in Human Health and Material Engineering” - Tremendous progress has been made in the past decade in understanding the importance of the gut microbiome in human health. However, there is currently a lack of comprehensive review that combines the fields of gut microbiome and material research. This paper aims to bridge the gap by discussing critical aspects of material engineering in the gut microbiome and human health. The research tools for gut microbiome research and therapeutics development are presented, including biomaterial technologies such as intestinal organoids, gut-on-chip models, and microbiome biosensors. The paper also emphasizes the importance of investigating and regulating the microbiome-gut-brain axis using biomaterials. Future directions and regulatory rules in clinical translation are also discussed.
Correction
Engineering, Biomedical
Ji-Young Yoon, Nandin Mandakhbayar, Jeongeun Hyun, Dong Suk Yoon, Kapil D. Patel, Keunsoo Kang, Hosup Shim, Hae-Hyoung Lee, Jung-Hwan Lee, Kam W. Leong, Hae-Won Kim
Article
Engineering, Biomedical
Ji-Young Yoon, Nandin Mandakhbayar, Jeongeun Hyun, Dong Suk Yoon, Kapil D. Patel, Keunsoo Kang, Ho-Shup Shim, Hae-Hyoung Lee, Jung-Hwan Lee, Kam W. Leong, Hae-Won Kim
Summary: Cell reprogramming can transform fibroblasts into osteogenic cells, providing a potential source of specialized cells for bone tissue engineering and disease modeling. A chemical cocktail was used to induce osteogenic differentiation, and the resulting cells showed characteristics of osteoblasts. The reprogrammed cells were able to form mineralized nodules and contributed to bone tissue formation in vivo.
Article
Engineering, Biomedical
Yawen Ma, Huimin Lin, Peng Wang, Haocheng Yang, Jie Yu, Hao Tian, Tianyu Li, Shengfang Ge, Yilong Wang, Renbing Jia, Kam W. Leong, Jing Ruan
Summary: MicroRNA-based gene therapy using biocompatible nanocarriers shows promise in treating ocular melanoma by up-regulating tumor suppressor miR-30a-5p and inhibiting malignant phenotypes. The nanocarrier with high miRNA loading and redox-responsive release capabilities enhances the therapeutic effect. Furthermore, it promotes M1 macrophage polarization and activates Fenton reaction, synergistically enhancing anti-tumor immunity. The study demonstrates the potential of this nanocarrier for targeted gene therapy in melanoma and other cancers.
ACTA BIOMATERIALIA
(2023)
Article
Chemistry, Multidisciplinary
Jiaqi Xu, Junchao Xu, Tongfei Shi, Yinlong Zhang, Fangman Chen, Chao Yang, Xinjing Guo, Guangna Liu, Dan Shao, Kam W. Leong, Guangjun Nie
Summary: Microbiota-based therapeutics offer innovative strategies to treat inflammatory bowel diseases (IBDs), but the clinical outcome and bacterial approach need improvement. Inspired by the benefits of probiotics, bioartificial probiotics are designed to restore intestinal microenvironment and shift the gut microbiome to an anti-inflammatory state. The bioartificial probiotic consists of E. coli Nissle 1917-derived membrane (EM) as the surface and biodegradable diselenide-bridged mesoporous silica nanoparticles (SeM) as the core. This work suggests a safe and effective nanomedicine for IBDs therapy.
ADVANCED MATERIALS
(2023)
Article
Engineering, Biomedical
Baoding Huang, Qianfen Wan, Tianyu Li, Lexiang Yu, Wen Du, Carmen Calhoun, Kam W. Leong, Li Qiang
Summary: As a solution to the chronic inflammation and local adiposity caused by obesity, cationic polyamidoamine (PAMAM) treatment has shown promising results in improving metabolic functions and reducing body weight in diet-induced obese (DIO) mice. The treatment involves the use of PAMAM generation 3 (P-G3) scavenger and complexing P-G3 with human serum albumin (HSA) to achieve sustained release. Local injection of HSA-PG3 successfully restricts the distribution of the complex within the targeted adipose tissue and reduces focal adiposity.
Article
Chemistry, Multidisciplinary
Naoto Yoshinaga, Joyce K. Zhou, Cong Xu, Chai Hoon Quek, Yuefei Zhu, Ding Tang, Lin Yung Hung, Sarah A. Najjar, Chin Ying Angela Shiu, Kara Gross Margolis, Yeh-Hsing Lao, Kam W. Leong
Summary: Effective delivery of CRISPR-Cas9 components is crucial and oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. In this study, we developed novel PBA-functionalized CS-PEI polymers for oral CRISPR delivery, which showed effective penetration in the intestinal mucosa and achieved downregulation of the target protein and reduction in cholesterol. This study demonstrates the potential of addressing the needs of gene editing in a patient-compliant manner.
Article
Engineering, Biomedical
Ganchimeg Davaa, Jin Young Hong, Jung-Hwan Lee, Min Soo Kim, Jennifer O. Buitrago, Yu-Meng Li, Hae-Hyoung Lee, Dong Wook Han, Kam W. Leong, Jung Keun Hyun, Hae-Won Kim
Summary: Neural stem cells (NSC) have the potential to regenerate injured neural tissues, but suffer from low survival and uncontrolled differentiation. This study demonstrates that mechanically-tuned protein hydrogels can protect and enhance the long-term survival of reprogrammed NSC, alleviate neural inflammation, promote differentiation, and improve locomotor functions in treating injured spinal cord.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cell Biology
Yunfei Li, Zhixiong Sun, Huixiang Zhu, Yan Sun, David B. Shteyman, Sander Markx, Kam W. Leong, Bin Xu, Bingmei M. Fu
Summary: The integrity of the blood-brain barrier formed by brain microvascular endothelial cells derived from 22q11.2 Deletion Syndrome patients is compromised. The haploinsufficiency of CRKL, a gene within the 22q11.2 DS deletion region, contributes to this deficit. Treatment with imatinib, an FDA-approved drug, restores the compromised blood-brain barrier by increasing the level of active forms of the CRKL protein.
Article
Engineering, Biomedical
Hye Sung Kim, Tzu-Chieh Ho, Moshe J. Willner, Michael W. Becker, Hae-Won Kim, Kam W. Leong
Summary: In this study, we propose an ex vivo T cell expansion system that mimics natural antigen-presenting cells for adoptive cell therapy. The system utilizes microfiber scaffolds coated with dendritic cell membrane to replicate the physicochemical properties of dendritic cells, leading to greater expansion and functionality of T cells. This scalable and customizable platform holds promise for future research and application in cell therapy.
BIOACTIVE MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Yongqiang Xiao, He Fang, Yuefei Zhu, Jie Zhou, Zhanzhan Dai, Hongxia Wang, Zhaofan Xia, Zhaoxu Tu, Kam W. Leong
Summary: This study investigates the effectiveness of cationic hyperbranched polyaminoglycosides derived from tobramycin (HPT) and disulfide-included HPT (ss-HPT) in scavenging cell-free nucleic acids (cfNAs) to mitigate posttrauma inflammation and hypercoagulation. Both polymers demonstrate the ability to suppress inflammation and hypercoagulation by efficiently scavenging cfNAs, and exhibit potent antibacterial effects. Additionally, these polymers exhibit favorable modulatory effects on inflammation and therapeutic outcomes in a mouse model. Notably, ss-HPT shows high accumulation and retention in injured organs of traumatized mice, with a higher biodegradation rate in healthy mice compared to HPT.
Article
Multidisciplinary Sciences
Qin Fan, Huaxing Dai, Jinyu Bai, Jialu Xu, Qingle Ma, Ziying Fei, Xiaozhong Zhou, Kam W. Leong, Chao Wang
Summary: Implanted biomaterials may create an immunosuppressive microenvironment, but vitamin C treatment can alleviate this condition and reduce the risk of malignant cell survival around the implants.
FUNDAMENTAL RESEARCH
(2022)
Meeting Abstract
Cell & Tissue Engineering
Kam Leong
TISSUE ENGINEERING PART A
(2022)
Correction
Chemistry, Multidisciplinary
Ya-Ru Zhang, Jia-Qi Luo, Jia-Xian Li, Qiu-Yue Huang, Xiao-Xiao Shi, Yong-Cong Huang, Kam W. Leong, Wei-ling He, Jin-Zhi Du