Medicine, Research & Experimental

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Article Biochemistry & Molecular Biology

Acute and postacute sequelae associated with SARS-CoV-2 reinfection

Benjamin Bowe, Yan Xie, Ziyad Al-Aly

Summary: A new analysis using US Department of Veterans Affairs databases showed that reinfection is associated with increased risk of all-cause mortality, hospitalization and a wide range of long COVID complications in individuals who have had SARS-CoV-2 compared to those with no reinfection.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

Keith Sacco, Riccardo Castagnoli, Svetlana Vakkilainen, Can Liu, Ottavia M. Delmonte, Cihan Oguz, Ian M. Kaplan, Sara Alehashemi, Peter D. Burbelo, Farzana Bhuyan, Adriana A. de Jesus, Kerry Dobbs, Lindsey B. Rosen, Aristine Cheng, Elana Shaw, Mikko S. Vakkilainen, Francesca Pala, Justin Lack, Yu Zhang, Danielle L. Fink, Vasileios Oikonomou, Andrew L. Snow, Clifton L. Dalgard, Jinguo Chen, Brian A. Sellers, Gina A. Montealegre Sanchez, Karyl Barron, Emma Rey-Jurado, Cecilia Vial, Maria Cecilia Poli, Amelia Licari, Daniela Montagna, Gian Luigi Marseglia, Francesco Licciardi, Ugo Ramenghi, Valentina Discepolo, Andrea Lo Vecchio, Alfredo Guarino, Eli M. Eisenstein, Luisa Imberti, Alessandra Sottini, Andrea Biondi, Sayonara Mato, Dana Gerstbacher, Meng Truong, Michael A. Stack, Mary Magliocco, Marita Bosticardo, Tomoki Kawai, Jeffrey J. Danielson, Tyler Hulett, Manor Askenazi, Shaohui Hu, Jeffrey Cohen, Helen C. Su, Douglas B. Kuhns, Michail S. Lionakis, Thomas M. Snyder, Steven M. Holland, Raphaela Goldbach-Mansky, John S. Tsang, Luigi D. Notarangelo

Summary: Transcriptomic, proteomic and immune repertoire profiling revealed distinct peripheral features of MIS-C and pediatric COVID-19, providing valuable insights into the pathophysiology and potential therapeutic strategies for these disorders.

NATURE MEDICINE (2022)

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Review Biochemistry & Molecular Biology

Misinformation: susceptibility, spread, and interventions to immunize the public

Sander van der Linden

Summary: The spread of misinformation poses a significant threat to public health and global pandemic management. This review provides an overview of the psychology of misinformation, covering susceptibility, spread, and intervention measures.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy

Melody Smith, Anqi Dai, Guido Ghilardi, Kimberly Amelsberg, Sean M. Devlin, Raymone Pajarillo, John B. Slingerland, Silvia Beghi, Pamela S. Herrera, Paul Giardina, Annelie Clurman, Emmanuel Dwomoh, Gabriel Armijo, Antonio L. C. Gomes, Eric R. Littmann, Jonas Schluter, Emily Fontana, Ying Taur, Jae H. Park, Maria Lia Palomba, Elizabeth Halton, Josel Ruiz, Tania Jain, Martina Pennisi, Aishat Olaide Afuye, Miguel-Angel Perales, Craig W. Freyer, Alfred Garfall, Shannon Gier, Sunita Nasta, Daniel Landsburg, James Gerson, Jakub Svoboda, Justin Cross, Elise A. Chong, Sergio Giralt, Saar Gill, Isabelle Riviere, David L. Porter, Stephen J. Schuster, Michel Sadelain, Noelle Frey, Renier J. Brentjens, Carl H. June, Eric G. Pamer, Jonathan U. Peled, Andrea Facciabene, Marcel R. M. van den Brink, Marco Ruella

Summary: This study investigated the changes in the intestinal microbiome of patients with B cell lymphoma and leukemia after receiving anti-CD19 CAR T cell therapy, and found that these changes are associated with clinical outcomes.

NATURE MEDICINE (2022)

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Article Medicine, Research & Experimental

Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms

Hasan Slika, Hadi Mansour, Nadine Wehbe, Suzanne A. Nasser, Rabah Iratni, Gheyath Nasrallah, Abdullah Shaito, Tarek Ghaddar, Firas Kobeissy, Ali H. Eid

Summary: Cancer is a major cause of global morbidity and mortality. Flavonoids are natural polyphenols with established anticancer and antioxidant capacities. They can inhibit carcinogenesis by suppressing reactive oxygen species (ROS), but also induce cancer cell death through excessive oxidative stress. This review explores the antioxidant capacity and pro-oxidant roles of flavonoids, as well as their pathways in cancer prevention and treatment. The review also emphasizes the anticancer functions of specific flavonoids in various cancers and their structure-function relations.

BIOMEDICINE & PHARMACOTHERAPY (2022)

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Article Cell Biology

mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 omicron variant

Venkata-Viswanadh Edara, Kelly E. Manning, Madison Ellis, Lilin Lai, Kathryn M. Moore, Stephanie L. Foster, Katharine Floyd, Meredith E. Davis-Gardner, Grace Mantus, Lindsay E. Nyhoff, Sarah Bechnak, Ghina Alaaeddine, Amal Naji, Hady Samaha, Matthew Lee, Laurel Bristow, Matthew Gagne, Jesmine Roberts-Torres, Amy R. Henry, Sucheta Godbole, Arash Grakoui, Marybeth Saxton, Anne Piantadosi, Jesse J. Waggoner, Daniel C. Douek, Nadine Rouphael, Jens Wrammert, Mehul S. Suthar

Summary: The study indicates that a two-dose vaccination may not provide sufficient neutralizing antibody responses against the omicron variant, with a significant reduction in neutralizing activity observed after six months. However, COVID-19-recovered individuals still retain some level of neutralizing antibody responses. A third dose (booster shot) is necessary to enhance the neutralizing activity against the omicron variant.

CELL REPORTS MEDICINE (2022)

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Review Medicine, Research & Experimental

Nrf2/Keap1/ARE signaling: Towards specific regulation

Alexey Ulasov, Andrey A. Rosenkranz, Georgii P. Georgiev, Alexander S. Sobolev

Summary: The Nrf2 transcription factor regulates the expression of genes involved in cell defense against oxidative stress, which is associated with various diseases. The interactions between Nrf2 and Keap1 protein play a crucial role in this regulation. The activation of the Nrf2 system is considered as a promising strategy to treat diseases related to oxidative stress, including COVID-19. Two approaches are being developed to inactivate the Keap1 guardian function and enhance Nrf2 activity.

LIFE SCIENCES (2022)

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Review Biochemistry & Molecular Biology

Targeting the gut and tumor microbiota in cancer

Elizabeth M. Park, Manoj Chelvanambi, Neal Bhutiani, Guido Kroemer, Laurence Zitvogel, Jennifer A. Wargo

Summary: This review highlights the potential of targeting microorganisms in personalized cancer care, the impact of microbes on cancer immunosurveillance and immunotherapy, and the development of novel therapeutic strategies targeting the microbiota. Evaluating a patient's microbial composition and function will be crucial in future multidisciplinary and precision medicine approaches.

NATURE MEDICINE (2022)

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Review Medicine, Research & Experimental

The Gut-Brain Axis

Emeran A. Mayer, Karina Nance, Shelley Chen

Summary: Preclinical evidence has shown bidirectional interactions among the brain, gut, and gut microbiome, with candidate signaling molecules and three communication channels. Alterations in gut-brain-microbiome interactions have been found in various disorders, but the causative role of the microbiome in irritable bowel syndrome is still unclear. Current therapies are limited to dietary interventions and targeted pharmacological and behavioral approaches. Further research and randomized controlled trials are needed for effective therapies.

ANNUAL REVIEW OF MEDICINE (2022)

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Article Biochemistry & Molecular Biology

A roadmap to increase diversity in genomic studies

Segun Fatumo, Tinashe Chikowore, Ananyo Choudhury, Muhammad Ayub, Alicia R. Martin, Karoline Kuchenbaecker

Summary: This article describes the factors contributing to the imbalance in representation of different populations in genetic and genomic studies, and proposes a roadmap to enhance inclusion and ensure equal health benefits of genomics advances. The authors emphasize the importance of global efforts to ensure that everyone can benefit from genomic medicine.

NATURE MEDICINE (2022)

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Review Medicine, General & Internal

Therapeutic targeting of undruggable MYC

Victor Llombart, Marc R. Mansour

Summary: c-MYC plays a crucial role in regulating gene expression and is involved in tumor initiation and maintenance. Inhibition of MYC shows promising anti-proliferative effects and tumor regression, making it a potential therapeutic target for cancer treatment.

EBIOMEDICINE (2022)

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Article Biochemistry & Molecular Biology

COVID-19 and resilience of healthcare systems in ten countries

Catherine Arsenault, Anna Gage, Min Kyung Kim, Neena R. Kapoor, Patricia Akweongo, Freddie Amponsah, Amit Aryal, Daisuke Asai, John Koku Awoonor-Williams, Wondimu Ayele, Paula Bedregal, Svetlana Doubova, Mahesh Dulal, Dominic Dormenyo Gadeka, Georgiana Gordon-Strachan, Damen Haile Mariam, Dilipkumar Hensman, Jean Paul Joseph, Phanuwich Kaewkamjornchai, Munir Kassa Eshetu, Solomon Kassahun Gelaw, Shogo Kubota, Borwornsom Leerapan, Paula Margozzini, Anagaw Derseh Mebratie, Suresh Mehata, Mosa Moshabela, Londiwe Mthethwa, Adiam Nega, Juhwan Oh, Sookyung Park, Alvaro Passi-Solar, Ricardo Perez-Cuevas, Alongkhone Phengsavanh, Tarylee Reddy, Thanitsara Rittiphairoj, Jaime C. Sapag, Roody Thermidor, Boikhutso Tlou, Francisco Valenzuela Guinez, Sebastian Bauhoff, Margaret E. Kruk

Summary: The study found that the COVID-19 pandemic had varying disruptions on health services in 31 countries, affecting cancer screenings, TB screenings, and HIV testing the most. Maternal health services and child vaccinations were also impacted, with some countries still experiencing severe disruptions in healthcare services.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

Nicole L. Welch, Meilin Zhu, Catherine Hua, Juliane Weller, Marzieh Ezzaty Mirhashemi, Tien G. Nguyen, Sreekar Mantena, Matthew R. Bauer, Bennett M. Shaw, Cheri M. Ackerman, Sri Gowtham Thakku, Megan W. Tse, Jared Kehe, Marie-Martine Uwera, Jacqueline S. Eversley, Derek A. Bielwaski, Graham McGrath, Joseph Braidt, Jeremy Johnson, Felecia Cerrato, Gage K. Moreno, Lydia A. Krasilnikova, Brittany A. Petros, Gabrielle L. Gionet, Ewa King, Richard C. Huard, Samantha K. Jalbert, Michael L. Cleary, Nicholas A. Fitzgerald, Stacey B. Gabriel, Glen R. Gallagher, Sandra C. Smole, Lawrence C. Madoff, Catherine M. Brown, Matthew W. Keller, Malania M. Wilson, Marie K. Kirby, John R. Barnes, Daniel J. Park, Katherine J. Siddle, Christian T. Happi, Deborah T. Hung, Michael Springer, Bronwyn L. MacInnis, Jacob E. Lemieux, Eric Rosenberg, John A. Branda, Paul C. Blainey, Pardis C. Sabeti, Cameron Myhrvold

Summary: A microfluidic CRISPR-based platform called mCARMEN enables multiplexed and high-throughput identification of a wide range of respiratory viruses, including specific SARS-CoV-2 variants. The platform combines cost-effectiveness, diagnostic-grade performance, and a streamlined workflow for clinical use.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Increased global integration in the brain after psilocybin therapy for depression

Richard E. Daws, Christopher Timmermann, Bruna Giribaldi, James D. Sexton, Matthew B. Wall, David Erritzoe, Leor Roseman, David Nutt, Robin Carhart-Harris

Summary: Psilocybin therapy has the potential to treat depression by increasing brain network integration, according to two clinical trials. The antidepressant response to psilocybin was rapid and sustained, while escitalopram had milder effects on brain network organization.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a)

Michael J. Koren, Patrick Maurice Moriarty, Seth J. Baum, Joel Neutel, Martha Hernandez-Illas, Howard S. Weintraub, Monica Florio, Helina Kassahun, Stacey Melquist, Tracy Varrieur, Saptarsi M. Haldar, Winnie Sohn, Huei Wang, Mary Elliott-Davey, Brooke M. Rock, Tao Pei, Oliver Homann, Jennifer Hellawell, Gerald F. Watts

Summary: This study reports the discovery and development of a new drug, olpasiran, which can directly inhibit the translation of Lp(a) messenger RNA, leading to a significant reduction in plasma Lp(a) concentration. In animal and human trials, olpasiran demonstrated good safety and tolerability, and maintained a sustained reduction in high plasma Lp(a) concentration.

NATURE MEDICINE (2022)

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Article Medicine, Research & Experimental

Mendelian Randomization: Concepts and Scope

Rebecca C. Richmond, George Davey Smith

Summary: Mendelian randomization (MR) is a method for studying the causal effects of modifiable exposures on health, social, and economic outcomes using genetic variants. By using randomly inherited genetic variants as a tool, MR provides a more accurate estimation of the relationship between risk factors and outcomes, reducing confounding and bias. As genetic data and resources become more abundant and accessible, the scope of MR applications continues to expand.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2022)

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Article Cell Biology

Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors

Diana Tavares-Ferreira, Stephanie Shiers, Pradipta R. Ray, Andi Wangzhou, Vivekanand Jeevakumar, Ishwarya Sankaranarayanan, Anna M. Cervantes, Jeffrey C. Reese, Alexander Chamessian, Bryan A. Copits, Patrick M. Dougherty, Robert W. Gereau, Michael D. Burton, Gregory Dussor, Theodore J. Price

Summary: Nociceptors, specialized sensory neurons, play a crucial role in detecting and generating pain signals. This study used spatial transcriptomics to characterize the transcriptomes of human nociceptors, identifying different clusters and potential drug targets in the human dorsal root ganglia (DRG). Comparison with mouse sensory neuron transcriptomes and nonhuman primate DRG neuronal subtypes revealed conserved gene expression patterns but also species-specific differences. Sex differences in DRG subpopulation transcriptomes were also identified. This comprehensive spatial characterization of human nociceptors has significant implications for the development of improved treatments for pain disorders.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Cell Biology

The IL-1?, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19

Christoph Schultheiss, Edith Willscher, Lisa Paschold, Cornelia Gottschick, Bianca Klee, Svenja-Sibylla Henkes, Lidia Bosurgi, Jochen Dutzmann, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. Hoell, Michael Gekle, Rafael Mikolajczyk, Mascha Binder

Summary: Post-acute sequelae of COVID-19 (PASC) is a global problem with unknown molecular drivers. A study found that 67.8% of participants, mostly with mild infections, reported PASC, with symptoms including fatigue, dyspnea, and concentration deficit. These symptoms persisted in 60% of participants over an average 8-month follow-up period. PASC was associated with elevated plasma levels of IL-18, IL-6, and TNF.

CELL REPORTS MEDICINE (2022)

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Article Biochemistry & Molecular Biology

T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma

Alexander X. Lozano, Aadel A. Chaudhuri, Aishwarya Nene, Antonietta Bacchiocchi, Noah Earland, Matthew D. Vesely, Abul Usmani, Brandon E. Turner, Chloe B. Steen, Bogdan A. Luca, Ti Badri, Gunsagar S. Gulati, Milad R. Vahid, Farnaz Khameneh, Peter K. Harris, David Y. Chen, Kavita Dhodapkar, Mario Sznol, Ruth Halaban, Aaron M. Newman

Summary: This study provides new insights into the immunological state prior to the development of immune-related adverse events (irAEs) in patients with melanoma treated with immune checkpoint inhibitors (ICIs). The abundance of activated CD4 memory T cells and T cell receptor diversity in the blood samples were found to be associated with severe irAEs, regardless of the affected organ system. The study also investigated the changes in T cell receptor clonality during combination therapy and linked them to the severity and timing of irAE onset. These findings have implications for improved diagnostics and clinical management of irAEs.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines

Jia Wei, Koen B. Pouwels, Nicole Stoesser, Philippa C. Matthews, Ian Diamond, Ruth Studley, Emma Rourke, Duncan Cook, John Bell, John N. Newton, Jeremy Farrar, Alison Howarth, Brian D. Marsden, Sarah Hoosdally, E. Yvonne Jones, David Stuart, Derrick W. Crook, Tim E. A. Peto, A. Sarah Walker, David W. Eyre

Summary: This study investigated the antibody responses and protection following the second doses of ChAdOx1 or BNT162b2 vaccines against SARS-CoV-2 in the general population of the United Kingdom. The results showed significant boosting of anti-spike IgG antibody levels after the second doses of both vaccines, with BNT162b2 generating higher peak levels than ChAdOX1. Older individuals, males, and prior infection influenced the antibody levels. The levels of anti-spike IgG were associated with protection from infection after vaccination, and previous infection enhanced antibody peak levels and half-life. At least 67% protection against infection is estimated to last for 2-3 months after two ChAdOx1 doses, 5-8 months after two BNT162b2 doses in uninfected individuals, and 1-2 years after natural infection in unvaccinated individuals. A third booster dose may be necessary, prioritizing ChAdOx1 recipients and those more clinically vulnerable.

NATURE MEDICINE (2022)

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