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Full-Text Articles in Medicine and Health Sciences

Oral Lactoferrin Administration Does Not Impact The Diversity Or Composition Of The Infant Gut Microbiota In A Peruvian Cohort, Luis González, Jose Luis Paredes Sosa, Susan Mosquito, Yesenia Filio, Pedro E Romero, Theresa J Ochoa, Pablo Tsukayama Dec 2023

Oral Lactoferrin Administration Does Not Impact The Diversity Or Composition Of The Infant Gut Microbiota In A Peruvian Cohort, Luis González, Jose Luis Paredes Sosa, Susan Mosquito, Yesenia Filio, Pedro E Romero, Theresa J Ochoa, Pablo Tsukayama

Journal Articles

Previous studies have suggested that oral lactoferrin enhances diversity in the gut microbiota in infants while inhibiting the growth of opportunistic pathogens. However, the effect of lactoferrin on infant gut microbiota over time has yet to be thoroughly studied. Our study suggests that lactoferrin oral treatment in infants aged 12-18 months does not affect gut microbiome diversity and composition over time. to our knowledge, this is the first study to report the effect of lactoferrin on infant gut microbiome composition over time and helps elucidate its impact on infant health and its therapeutic potential.


Gut Microbiota Composition And Diversity Before, During, And Two Months After Rifamycin-Based Tuberculosis Preventive Therapy, Marie Nancy Séraphin, Julia Bellot, Emily Klann, Maria Ukhanova, Florence G Saulsberry, Charles A Peloquin, Volker Mai Nov 2023

Gut Microbiota Composition And Diversity Before, During, And Two Months After Rifamycin-Based Tuberculosis Preventive Therapy, Marie Nancy Séraphin, Julia Bellot, Emily Klann, Maria Ukhanova, Florence G Saulsberry, Charles A Peloquin, Volker Mai

Journal Articles

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after …


Coordination Between Aminoacylation And Editing To Protect Against Proteotoxicity, Hong Zhang, Parker Murphy, Jason Yu, Sukyeong Lee, Francis T F Tsai, Ambro Van Hoof, Jiqiang Ling Oct 2023

Coordination Between Aminoacylation And Editing To Protect Against Proteotoxicity, Hong Zhang, Parker Murphy, Jason Yu, Sukyeong Lee, Francis T F Tsai, Ambro Van Hoof, Jiqiang Ling

Journal Articles

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that ligate amino acids to tRNAs, and often require editing to ensure accurate protein synthesis. Recessive mutations in aaRSs cause various neurological disorders in humans, yet the underlying mechanism remains poorly understood. Pathogenic aaRS mutations frequently cause protein destabilization and aminoacylation deficiency. In this study, we report that combined aminoacylation and editing defects cause severe proteotoxicity. We show that the ths1-C268A mutation in yeast threonyl-tRNA synthetase (ThrRS) abolishes editing and causes heat sensitivity. Surprisingly, experimental evolution of the mutant results in intragenic mutations that restore heat resistance but not editing. ths1-C268A destabilizes ThrRS and …


Genome-Wide Analysis Of The Interplay Between Chromatin-Associated Rna And 3d Genome Organization In Human Cells, Riccardo Calandrelli, Xingzhao Wen, John Lalith Charles Richard, Zhifei Luo, Tri C Nguyen, Chien-Ju Chen, Zhijie Qi, Shuanghong Xue, Weizhong Chen, Zhangming Yan, Weixin Wu, Kathia Zaleta-Rivera, Rong Hu, Miao Yu, Yuchuan Wang, Wenbo Li, Jian Ma, Bing Ren, Sheng Zhong Oct 2023

Genome-Wide Analysis Of The Interplay Between Chromatin-Associated Rna And 3d Genome Organization In Human Cells, Riccardo Calandrelli, Xingzhao Wen, John Lalith Charles Richard, Zhifei Luo, Tri C Nguyen, Chien-Ju Chen, Zhijie Qi, Shuanghong Xue, Weizhong Chen, Zhangming Yan, Weixin Wu, Kathia Zaleta-Rivera, Rong Hu, Miao Yu, Yuchuan Wang, Wenbo Li, Jian Ma, Bing Ren, Sheng Zhong

Journal Articles

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA …


Sepsis Exacerbates Alzheimer’S Disease Pathophysiology, Modulates The Gut Microbiome, Increases Neuroinflammation And Amyloid Burden, Vijayasree V Giridharan, Celso S G Catumbela, Carlos Henrique R Catalão, Juneyoung Lee, Bhanu P Ganesh, Fabricia Petronilho, Felipe Dal-Pizzol, Rodrigo Morales, Tatiana Barichello Oct 2023

Sepsis Exacerbates Alzheimer’S Disease Pathophysiology, Modulates The Gut Microbiome, Increases Neuroinflammation And Amyloid Burden, Vijayasree V Giridharan, Celso S G Catumbela, Carlos Henrique R Catalão, Juneyoung Lee, Bhanu P Ganesh, Fabricia Petronilho, Felipe Dal-Pizzol, Rodrigo Morales, Tatiana Barichello

Journal Articles

While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task …


New Insights Into Rna Processing By The Eukaryotic Trna Splicing Endonuclease, Cassandra K Hayne, Samoil Sekulovski, Jennifer E Hurtig, Robin E Stanley, Simon Trowitzsch, Ambro Van Hoof Sep 2023

New Insights Into Rna Processing By The Eukaryotic Trna Splicing Endonuclease, Cassandra K Hayne, Samoil Sekulovski, Jennifer E Hurtig, Robin E Stanley, Simon Trowitzsch, Ambro Van Hoof

Journal Articles

Through its role in intron cleavage, tRNA splicing endonuclease (TSEN) plays a critical function in the maturation of intron-containing pre-tRNAs. The catalytic mechanism and core requirement for this process is conserved between archaea and eukaryotes, but for decades, it has been known that eukaryotic TSENs have evolved additional modes of RNA recognition, which have remained poorly understood. Recent research identified new roles for eukaryotic TSEN, including processing or degradation of additional RNA substrates, and determined the first structures of pre-tRNA-bound human TSEN complexes. These recent discoveries have changed our understanding of how the eukaryotic TSEN targets and recognizes substrates. Here, …


Liposome-Based Carriers For Crispr Genome Editing, Xing Yin, Romain Harmancey, David D Mcpherson, Hyunggun Kim, Shao-Ling Huang Aug 2023

Liposome-Based Carriers For Crispr Genome Editing, Xing Yin, Romain Harmancey, David D Mcpherson, Hyunggun Kim, Shao-Ling Huang

Journal Articles

The CRISPR-based genome editing technology, known as clustered regularly interspaced short palindromic repeats (CRISPR), has sparked renewed interest in gene therapy. This interest is accompanied by the development of single-guide RNAs (sgRNAs), which enable the introduction of desired genetic modifications at the targeted site when used alongside the CRISPR components. However, the efficient delivery of CRISPR/Cas remains a challenge. Successful gene editing relies on the development of a delivery strategy that can effectively deliver the CRISPR cargo to the target site. To overcome this obstacle, researchers have extensively explored non-viral, viral, and physical methods for targeted delivery of CRISPR/Cas9 and …


Microbiome Alteration Via Fecal Microbiota Transplantation Is Effective For Refractory Immune Checkpoint Inhibitor-Induced Colitis, Taylor M Halsey, Anusha S Thomas, Tomo Hayase, Weijie Ma, Hamzah Abu-Sbeih, Baohua Sun, Edwin Roger Parra, Zhi-Dong Jiang, Herbert L Dupont, Christopher Sanchez, Rawan El-Himri, Alexandria Brown, Ivonne Flores, Lauren Mcdaniel, Miriam Ortega Turrubiates, Matthew Hensel, Dung Pham, Stephanie S Watowich, Eiko Hayase, Chia-Chi Chang, Robert R Jenq, Yinghong Wang Jun 2023

Microbiome Alteration Via Fecal Microbiota Transplantation Is Effective For Refractory Immune Checkpoint Inhibitor-Induced Colitis, Taylor M Halsey, Anusha S Thomas, Tomo Hayase, Weijie Ma, Hamzah Abu-Sbeih, Baohua Sun, Edwin Roger Parra, Zhi-Dong Jiang, Herbert L Dupont, Christopher Sanchez, Rawan El-Himri, Alexandria Brown, Ivonne Flores, Lauren Mcdaniel, Miriam Ortega Turrubiates, Matthew Hensel, Dung Pham, Stephanie S Watowich, Eiko Hayase, Chia-Chi Chang, Robert R Jenq, Yinghong Wang

Journal Articles

Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line …


Curated And Harmonized Gut Microbiome 16s Rrna Amplicon Data From Dietary Fiber Intervention Studies In Humans, Cynthia I Rodriguez, Ali Keshavarzian, Bruce R Hamaker, Feitong Liu, Genelle R Lunken, Heather Rasmussen, Hongwei Zhou, Julien Tap, Kelly S Swanson, Maria Ukhanova, Marion Leclerc, Martin Gotteland, Paola Navarrete, Petia Kovatcheva-Datchary, Wendy J Dahl, Jennifer B H Martiny Jun 2023

Curated And Harmonized Gut Microbiome 16s Rrna Amplicon Data From Dietary Fiber Intervention Studies In Humans, Cynthia I Rodriguez, Ali Keshavarzian, Bruce R Hamaker, Feitong Liu, Genelle R Lunken, Heather Rasmussen, Hongwei Zhou, Julien Tap, Kelly S Swanson, Maria Ukhanova, Marion Leclerc, Martin Gotteland, Paola Navarrete, Petia Kovatcheva-Datchary, Wendy J Dahl, Jennifer B H Martiny

Journal Articles

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide …


Glial Progenitor Heterogeneity And Key Regulators Revealed By Single-Cell Rna Sequencing Provide Insight To Regeneration In Spinal Cord Injury, Haichao Wei, Xizi Wu, Joseph Withrow, Raquel Cuevas-Diaz Duran, Simranjit Singh, Lesley S Chaboub, Jyotirmoy Rakshit, Julio Mejia, Andrew Rolfe, Juan J Herrera, Philip J Horner, Jia Qian Wu May 2023

Glial Progenitor Heterogeneity And Key Regulators Revealed By Single-Cell Rna Sequencing Provide Insight To Regeneration In Spinal Cord Injury, Haichao Wei, Xizi Wu, Joseph Withrow, Raquel Cuevas-Diaz Duran, Simranjit Singh, Lesley S Chaboub, Jyotirmoy Rakshit, Julio Mejia, Andrew Rolfe, Juan J Herrera, Philip J Horner, Jia Qian Wu

Journal Articles

Recent studies have revealed the heterogeneous nature of astrocytes; however, how diverse constituents of astrocyte-lineage cells are regulated in adult spinal cord after injury and contribute to regeneration remains elusive. We perform single-cell RNA sequencing of GFAP-expressing cells from sub-chronic spinal cord injury models and identify and compare with the subpopulations in acute-stage data. We find subpopulations with distinct functional enrichment and their identities defined by subpopulation-specific transcription factors and regulons. Immunohistochemistry, RNAscope experiments, and quantification by stereology verify the molecular signature, location, and morphology of potential resident neural progenitors or neural stem cells in the adult spinal cord before …


Lipid Nanoparticle-Mediated Mrna Delivery In Lung Fibrosis, Matteo Massaro, Suhong Wu, Gherardo Baudo, Haoran Liu, Scott Collum, Hyunho Lee, Cinzia Stigliano, Victor Segura-Ibarra, Harry Karmouty-Quintana, Elvin Blanco Apr 2023

Lipid Nanoparticle-Mediated Mrna Delivery In Lung Fibrosis, Matteo Massaro, Suhong Wu, Gherardo Baudo, Haoran Liu, Scott Collum, Hyunho Lee, Cinzia Stigliano, Victor Segura-Ibarra, Harry Karmouty-Quintana, Elvin Blanco

Journal Articles

mRNA delivery enables the specific synthesis of proteins with therapeutic potential, representing a powerful strategy in diseases lacking efficacious pharmacotherapies. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by excessive extracellular matrix (ECM) deposition and subsequent alveolar remodeling. Alveolar epithelial type 2 cells (AEC2) and fibroblasts represent important targets in IPF given their role in initiating and driving aberrant wound healing responses that lead to excessive ECM deposition. Our objective was to examine a lipid nanoparticle (LNP)-based mRNA construct as a viable strategy to target alveolar epithelial cells and fibroblasts in IPF. mRNA-containing LNPs measuring ∼34 nm had …