Article
Immunology
Sharat Srinivasula, Paula Degrange, Simone Perazzolo, Andrew Bonvillain, Amanda Tobery, Jacob Kaplan, Hyukjin Jang, Refika Turnier, Michael Davies, Mackenzie Cottrell, Rodney J. Y. Ho, Michele Di Mascio
Summary: This study investigates the relationship between immunovirological factors and antiretroviral (ARV) drug levels in lymph nodes (LN) during HIV therapy. The results show that intracellular active drug-metabolite (IADM) levels in lymph node mononuclear cells (LNMC) are significantly lower than in peripheral blood mononuclear cells (PBMC). The levels of IADM increase in both LNMC and PBMC over time, with a steeper increase in LNMC. There is a negative correlation between viral dissemination and IADM levels at the start of antiretroviral therapy. Simulation models suggest that reduced immune activation improves the formation of active drug-metabolites. These findings have implications for the efficacy of antiviral therapies targeting pathogenic viruses in highly inflammatory anatomical compartments.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Erin M. B. Scholz, Joseph N. Mwangi, Gabriela De la Cruz, Michael Nekorchuk, Chi Ngai Chan, Kathleen Busman-Sahay, Lourdes Adamson, Paul Luciw, Yuri Fedoriw, Jacob D. Estes, Elias P. Rosen, Angela D. M. Kashuba
Summary: Our study found that a significant portion of mesenteric lymph node tissue was not covered by any antiretroviral drugs, and a substantial amount of FDC-trapped virions and infected cells were not exposed to detected ARVs. While cumulative antiretroviral therapy coverage was high, a large portion of tissue coverage was from only one ARV, mainly maraviroc. Collagen deposition did not influence the heterogeneity of ARV distribution. Our findings suggest that ARV distribution, in addition to total-tissue drug concentration, is important when evaluating viral persistence in lymph nodes and other reservoir tissues.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Jianan Sang, Daohua Zhuang, Tao Zhang, Qunfu Wu, Jiangkun Yu, Zhigang Zhang
Summary: This study provides a comprehensive investigation of the gut microbiota's age patterning in four human populations and three nonhuman primates, and identifies Prevotellamassilia, Prevotella, Gemmiger, Coprococcus, Faecalibacterium, and Roseburia as potential common antiaging microbial markers in both humans and nonhuman primates due to their metabolic capabilities for host health benefits. The results also support the use of macaques as animal models for studying the role of the gut microbiome in human aging.
Article
Immunology
Natalia C. C. de Azevedo Fernandes, Juliana M. Guerra, Josue Diaz-Delgado, Mariana S. Cunha, Leila del C. Saad, Silvia D. Iglezias, Rodrigo A. Ressio, Cinthya dos Santos Cirqueira, Cristina T. Kanamura, Isis P. Jesus, Adriana Y. Maeda, Fernanda G. S. Vasami, Julia de Carvalho, Leonardo J. T. de Araujo, Renato Pereira de Souza, Juliana S. Nogueira, Roberta M. F. Spinola, Jose L. Catao-Dias
Summary: The study identified different profiles of yellow fever (YF) among different genera of primates in Brazil, with howler monkeys being the most reliable sentinel; capuchin and titi monkeys having higher viral loads but lower mortality rates; marmosets being the least sensitive, with lower viral loads, mortality rates, and no visible YF virus antigen despite detectable viral RNA. These differences should be taken into consideration in YF surveillance and control measures.
EMERGING INFECTIOUS DISEASES
(2021)
Review
Pharmacology & Pharmacy
Zesheng Cheng, Haiying Que, Li Chen, Qiu Sun, Xiawei Wei
Summary: The lymphatic system is crucial for maintaining humoral balance, lipid metabolism, and immune regulation. Lymph nodes, known as primary sites of tumor metastasis, have a significant impact on patient prognosis. Recent advancements in nanotechnology and biomaterials have led to the development of lymph-node-targeted drug-delivery systems, which hold promise for disease diagnosis and tumor therapy.
Article
Cell Biology
Martyna Okuniewska, Victoria Fang, Audrey Baeyens, Varsha Raghavan, June-Yong Lee, Dan R. Littman, Susan R. Schwab
Summary: The text discusses the role of S1P receptor 1 in T cell exit from lymph nodes and vascular permeability regulation. It also highlights the therapeutic potential of targeting S1PR1 for autoimmune diseases. The importance of SPNS2 in supplying lymph S1P and supporting T cell exit is emphasized, but further research is needed to determine its necessity during immune responses.
Article
Immunology
Qinhai Ma, Runfeng Li, Jianmin Guo, Man Li, Lin Ma, Jun Dai, Yongxia Shi, Jinlong Dai, Yuankeng Huang, Cailing Dai, Weiqi Pan, Huiling Zhong, Hong Zhang, Jian Wen, Haoting Zhao, Linping Wu, Wei Yang, Biliang Zhang, Zifeng Yang
Summary: RBMRNA-176 is a broad-spectrum and protective vaccine candidate for COVID-19 that can generate high titer antibodies and neutralize different variants of SARS-CoV-2. It also demonstrates effective control of viral replication and lung injury in animal studies.
Article
Biology
Ziqi Yu, Xiaoyang Han, Wenjing Xu, Jie Zhang, Carsten Marr, Dinggang Shen, Tingying Peng, Xiao-Yong Zhang, Jianfeng Feng
Summary: This study proposes a domain-adaptive and semi-supervised deep neural network called Brain Extraction Net (BEN) for extracting brain tissues across species, MRI modalities, and MR scanners. Compared to conventional toolboxes, BEN demonstrates superior robustness, accuracy, and generalizability.
Article
Zoology
Roberio Freire Filho, Carla Soraia Soares de Castro, Catarina Casanova, Bruna Martins Bezerra
Summary: The study found that in three areas in northeastern Brazil, humans commonly utilize primates for food, pets, medicine and leisure activities. Despite some variations in different regions, there are similarities in the ways humans exploit primates.
Article
Multidisciplinary Sciences
Anthony M. Cadena, John D. Ventura, Peter Abbink, Erica N. Borducchi, Hubert Tuyishime, Noe B. Mercado, Victoria Walker-Sperling, Mazuba Siamatu, Po-Ting Liu, Abishek Chandrashekar, Joseph P. Nkolola, Katherine McMahan, Nicole Kordana, Venous Hamza, Esther A. Bondzie, Emily Fray, Mithra Kumar, Stephanie Fischinger, Sally A. Shin, Mark G. Lewis, Robert F. Siliciano, Galit Alter, Dan H. Barouch
Summary: The viral DNA is widely distributed in multiple tissues, while viral RNA is mainly restricted to lymph nodes. Under long-term ART suppression, persistent viral RNA transcription mainly occurs in secondary lymphoid organs.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Hacene Medkour, Inestin Amona, Jean Akiana, Younes Laidoudi, Bernard Davoust, Idir Bitam, Ismail Lafri, Anthony Levasseur, Georges Diatta, Cheikh Sokhna, R. Adriana Hernandez-Aguilar, Amanda Barciela, Slim Gorsane, Henri Banga-Mboko, Didier Raoult, Florence Fenollar, Oleg Mediannikov
Summary: The study investigated pathogenic bacteria in African NHPs and humans, finding that there is a potential exchange of pathogens between the two. Certain pathogens such as non-pallidum Treponema spp. and non-tuberculosis Mycobacterium spp. were common in both NHPs and humans. Additionally, some pathogenic bacteria were shared between humans and gorillas, emphasizing the need for attention to potential exchanges between different primate species.
YALE JOURNAL OF BIOLOGY AND MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Barbara Costa, Nuno Vale
Summary: This review focuses on the antiretroviral drug, total level of viral production, and effectiveness of immune responses, as they are all dynamically interrelated. Immunological and viral processes interact in complex and non-linear ways, which can be characterized using mathematical models for reliable analysis and quantitative forecasts. Immune response profiling and prioritizing treatments based on the inability to control immune response and prevent T cell exhaustion can enhance treatment efficacy and further research in this field. The review also provides examples of the effects of modeling immune response in viral infections and the impact of pharmaceuticals on immune response.
Article
Multidisciplinary Sciences
Anthony G. Boghdadi, Joshua Spurrier, Leon Teo, Mingfeng Li, Mario Skarica, Benjamin Cao, William C. Kwan, Tobias D. Merson, Susan K. Nilsson, Nenad Sestan, Stephen M. Strittmatter, James A. Bourne
Summary: This study characterizes marmoset astrocytes following brain injury using single nuclei transcriptomics and finds that NogoA-expressing astrocytes can limit macrophage infiltration, thus mediating an anti-inflammatory response.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Elias P. Rosen, Claire Deleage, Nicole White, Craig Sykes, Catherine Brands, Lourdes Adamson, Paul Luciw, Jacob D. Estes, Angela D. M. Kashuba
Summary: The study revealed heterogeneous distribution of ARVs in lymph nodes, with lower penetration of ARVs in infected animals compared to healthy animals, but no increase in collagen deposition was found. Some areas of LN tissue were not exposed to detectable ARVs, and regions associated with B cell follicles showed a significant reduction in drug concentration. Nearest neighbour analysis showed that a small percentage of target cells and cell-associated vRNA were not directly contiguous to any drug at concentrations above the IC50 value.
JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Shuai Liu, Xu Wang, Xueliang Yu, Qiang Cheng, Lindsay T. Johnson, Sumanta Chatterjee, Di Zhang, Sang M. Lee, Yehui Sun, Ting-Chih Lin, John L. Liu, Daniel J. Siegwart
Summary: The study introduces a rational design and combinatorial synthesis of zwitterionic phospholipidated polymers (ZPPs) for efficient mRNA delivery to spleen and lymph nodes, with potential for substantial immunotherapeutic applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Infectious Diseases
Craig Sykes, Brian Van Horne, Justin Jones, Angela D. M. Kashuba, Gregory Gatto, Ariane Van der Straten, Leah Johnson, Mackenzie L. Cottrell
Summary: This study investigated the phosphorylation of EFdA across commonly used animal species in drug development and found that EFdA-tp concentrations were lower in all species compared to humans. Additionally, PBMCs from rhesus macaques and dogs exhibited significantly higher dATP concentrations compared to human PBMCs.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Editorial Material
Immunology
Charles W. Flexner, Angela Kashuba
CURRENT OPINION IN HIV AND AIDS
(2022)
Article
Gastroenterology & Hepatology
Tahrima Kayes, Harry Crane, Allison Symonds, Julie Dumond, Mackenzie Cottrell, Julia Di Girolamo, Sicha Manandhar, Tien Huey Lim, Edward Gane, Angela Kashuba, Miriam T. Levy
Summary: This study evaluated the pharmacokinetics of tenofovir alafenamide (TAF) and tenofovir (TFV) in breast milk and found that the concentrations of TAF and TFV were low, with negligible exposure to breastfeeding infants. These findings support the use of TAF to prevent mother-to-child transmission of chronic hepatitis B.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Sara N. Salerno, Edmund Capparelli, Helen McIlleron, Jacqueline G. Gerhart, Julie B. Dumond, Angela D. M. Kashuba, Paolo Denti, Daniel Gonzalez
Summary: This study used physiologically based pharmacokinetic modeling to optimize the dosage of LPV/RTV in children with HIV/TB co-infection, achieving therapeutic levels of LPV trough concentrations.
Correction
Public, Environmental & Occupational Health
John T. Mitchell, Charles M. Burns, Breyah Atkinson, Mackenzie Cottrell, Justin K. Frye, Mehri S. McKellar, Angela D. M. Kashuba, F. Joseph McClernon, Nwora Lance Okeke
Editorial Material
Gastroenterology & Hepatology
Miriam T. Levy, Angela Kashuba, Edward Gane
Summary: This article is connected to the papers by Kayes et al.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Microbiology
Aaron S. Devanathan, Nicole R. White, Yury Desyaterik, Gabriela De la Cruz, Michael Nekorchuk, Margaret Terry, Kathleen Busman-Sahay, Lourdes Adamson, Paul Luciw, Yuri Fedoriw, Jacob D. Estes, Elias P. Rosen, Angela D. M. Kashuba
Summary: This study investigated the relationship between antiretroviral drugs (ARVs) and viral expression in the spleen. The results showed that there was a heterogeneous distribution of ARVs in the spleen, and this distribution could affect the persistence of the virus.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Daniel Weiner, J. Robert Powell, J. Herbert Patterson, Rachel Tyson, Anil Gehi, Stephan Moll, Robyn Konicki, Farah Al Qaraghuli, Kristen B. Campbell, Angela D. M. Kashuba, Daniel Gonzalez
Summary: This study demonstrates the use of a prior published rivaroxaban population PK model to predict exposure in real-world patients, and finds that the exposure for most individual patients is outside the reference range.
JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Manse Kim, Claire E. Johnson, Alan A. Schmalstig, Ayano Annis, Sarah E. Wessel, Brian Van Horn, Amanda Schauer, Agata A. Exner, Jason E. Stout, Angela Wahl, Miriam Braunstein, J. Victor Garcia, Martina Kovarova
Summary: This study develops a long-acting delivery system for the anti-tuberculosis drug rifabutin, which is made of biodegradable polymers and biocompatible solvents. The formulation shows high drug load and sustained drug release, and demonstrates translational potential in animal models.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Analytical
Amanda P. Schauer, Craig Sykes, Mackenzie L. Cottrell, Arkaitz Imaz, Daniel Podzamczer, Angela D. M. Kashuba
Summary: A fully validated LC-MS/MS method was developed for simultaneous measurement of BIC, DOR, and RAL in human plasma. This method can be used to assess the pharmacokinetics of two newly approved antiretrovirals or support therapeutic drug monitoring for modern antiretroviral therapy.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Pharmacology & Pharmacy
Aaron S. S. Devanathan, Julie B. B. Dumond, Daijha J. C. Anderson, Kristen Moody, Amanda J. J. Poliseno, Amanda P. P. Schauer, Craig Sykes, Cynthia L. L. Gay, Elias P. P. Rosen, Angela D. M. Kashuba, Mackenzie L. L. Cottrell
Summary: Tenofovir diphosphate (TFVdp), an active metabolite of oral HIV pre-exposure prophylaxis (PrEP), is measured in dried blood spots (DBS) to estimate adherence. However, the long half-life of TFVdp in whole blood may lead to misclassification after a change in adherence. Emtricitabine triphosphate (FTCtp), another metabolite of PrEP, has a shorter half-life in whole blood, but adherence thresholds are undefined. This study demonstrates the need for FTCtp to estimate recent adherence and the importance of individualized interpretation for event-driven PrEP adherence monitoring.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Medicine, General & Internal
Jennifer M. Zerbato, Anchalee Avihingsanon, Kasha P. Singh, Wei Zhao, Claire Deleage, Elias Rosen, Mackenzie L. Cottrell, Ajantha Rhodes, Ashanti Dantanarayana, Carolin Tumpach, Surekha Tennakoon, Megan Crane, David J. Price, Sabine Braat, Hugh Mason, Michael Roche, Angela D. M. Kashuba, Peter A. Revill, Jennifer Audsley, Sharon R. Lewin
Summary: This study investigated the persistence of HIV infection in the liver during antiretroviral therapy (ART). The study found that prior to ART, HIV DNA and RNA were detected in the liver tissue of some participants. After ART, low levels of HIV DNA were still observed in the liver tissue of some participants. This suggests that HIV may persist in the liver during ART and requires further investigation.
Article
Multidisciplinary Sciences
Isabella C. Young, Ivana Massud, Mackenzie L. Cottrell, Roopali Shrivastava, Panita Maturavongsadit, Alka Prasher, Andres Wong-Sam, Chuong Dinh, Tiancheng Edwards, Victoria Mrotz, James Mitchell, Josilene Nascimento Seixas, Aryani Pallerla, Allison Thorson, Amanda Schauer, Craig Sykes, Gabriela de la Cruz, Stephanie A. Montgomery, Angela D. M. Kashuba, Walid Heneine, Charles W. Dobard, Martina Kovarova, J. Victor Garcia, J. Gerardo Garcia-Lerma, S. Rahima Benhabbour
Summary: The authors developed an injectable, biodegradable, and removable in-situ forming implant (ISFI) that can release cabotegravir (CAB) for more than 6 months, protecting against HIV for an extended period. The implant was well-tolerated and provided complete protection against multiple rectal SHIV challenges in female macaques. This study supports the clinical use of CAB ISFIs for ultra-long-acting HIV pre-exposure prophylaxis (PrEP) in humans.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Yury Desyaterik, Joseph N. Mwangi, MaryPeace McRae, Austin M. Jones, Angela D. M. Kashuba, Elias P. Rosen
Summary: In this study, we developed a method to analyze the spatial distributions of morphine and abacavir in mouse brain tissue using IR-MALDESI and Q Exactive Plus mass spectrometer. By analyzing different Orbitrap mass spectrometry acquisition modes and evaluating them based on signal abundance and frequency of detection, we achieved higher sensitivity to morphine. Our results showed successful detection of morphine in mouse brain tissue, with the selected ion monitoring mode providing 2.5 times higher sensitivity than the full-scan mode. Furthermore, we found a high correlation between the distributions of morphine and abacavir, with a Pearson correlation coefficient of R = 0.87.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Erick Leung, Mackenzie Cottrell, Craig Sykes, Nicole White, Angela Kashuba, Julie Dumond
Summary: The use of mathematical modeling and simulation can predict outcomes of HIV pre-exposure prophylaxis regimens, aiding in optimizing drug dosage and dosing frequency to mitigate the risk of clinical trial failure.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)