Review
Pharmacology & Pharmacy
Zhen Tian, Xin-Tong Lu, Xun Jiang, Jiao Tian
Summary: The central nervous system (CNS) is extremely complex and lacks effective treatment options for related disorders. Natural compounds, such as Bryostatin-1, have broad cellular targets and show promise in their pharmacological effects on multiple neurological diseases. Preclinical studies and clinical trials have shown that Bryostatin-1 has potential therapeutic benefits for Alzheimer's disease, multiple sclerosis, fragile X syndrome, stroke, traumatic brain injury, and depression. It exhibits neuroprotective effects and improves deficits in spatial learning, cognitive function, memory, and other neurological functions caused by these diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Virology
Laurent Hany, Marc-Olivier Turmel, Corinne Barat, Michel Ouellet, Michel J. Tremblay
Summary: Although LRAs can efficiently reactivate latent CD4(+) T cells, their impact on HIV-1 infection and production in macrophages remains unclear. This study found that certain LRAs exhibit antireplicative features in human macrophages and identified a new viral production inhibition mechanism by bryostatin-1 specific to myeloid cells. Further research is needed to fully assess the efficacy of HIV-1 eradicating strategies.
JOURNAL OF VIROLOGY
(2022)
Article
Plant Sciences
Haitao Zhang, Jinfeng Cai, Chunna Li, Lisi Deng, Hongqiong Zhu, Ting Huang, Jiacong Zhao, Jiasheng Zhou, Kai Deng, Zhongsi Hong, Jinyu Xia
Summary: This study found that wogonin can suppress latent HIV-1 reactivation by inhibiting the expression of histone acetyltransferase p300 and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. This discovery holds promising significance for future applications in HIV-1 functional cure.
Article
Biochemistry & Molecular Biology
Haruki Kitamura, Sayaka Sukegawa, Kouki Matsuda, Kousuke Tanimoto, Takuya Kobayakawa, Kazuho Takahashi, Hirokazu Tamamura, Kiyoto Tsuchiya, Hiroyuki Gatanaga, Kenji Maeda, Hiroaki Takeuchi
Summary: Combinational antiretroviral therapy (cART) successfully suppresses viral load but fails to eliminate HIV-1 reservoirs. "Shock and Kill" strategy using latently-reversing agents (LRAs) is being developed to reactivate latent HIV-1 and induce cell death. This study identified 4-phenylquinoline-8-amine (PQA) as a novel LRA candidate that effectively reactivated HIV-1 and induced cell death in latently-infected cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Microbiology
Ariane Zutz, Lin Chen, Franziska Sippl, Andreas Humpe, Christian Schoelz
Summary: The study focused on screening latent reservoirs in HIV-1 infected individuals and identified two novel compounds with high reactivation efficiency and low toxicity as potential new treatment options for reversing latency.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Immunology
Min Li, Marietta M. Budai, Min Chen, Jin Wang
Summary: The study presents a strategy called selective elimination of host cells harboring replication-competent HIV (SECH) that targets HIV-1 reservoirs through inhibition of autophagy and promotion of apoptosis. This strategy has been shown to effectively clear latent HIV-1 reservoirs in different subsets of T cells. The findings provide a potential method for eradicating HIV-1 infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Sushant Khanal, Madison Schank, Mohamed El Gazzar, Jonathan P. Moorman, Zhi Q. Yao
Summary: Eradication of latent HIV infection is a global health challenge, with popular strategies for HIV cure involving reactivation and killing of virus-infected cells. While antiretroviral therapy can halt HIV replication, it cannot completely eliminate latent proviruses, leading to reservoirs of infection that can cause cellular and systemic complications in HIV patients despite lack of active viral production. Studies into the mechanisms of HIV latency and reservoir formation are crucial for identifying strategies to eliminate viral reservoirs and ultimately cure HIV infection.
Article
Multidisciplinary Sciences
Alice Cho, Christian Gaebler, Thiago Olveira, Victor Ramos, Marwa Saad, Julio C. C. Lorenzi, Anna Gazumyan, Susan Moir, Marina Caskey, Tae-Wook Chun, Michel C. Nussenzweig
Summary: HIV-1 infection leads to the formation of a long-lasting reservoir of latently infected CD4(+) T cells, consisting of intact and defective proviruses. This study used Q4PCR to quantify the reservoir content and found that the defective reservoir remained stable while the intact proviral reservoir decayed over time. Both the intact and defective proviral reservoirs showed dynamic changes, with an enrichment of intact proviruses in expanded CD4(+) T cell clones and a decrease in overall reservoir complexity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Emily Cruz-Lorenzo, Nora-Guadalupe P. Ramirez, Jeon Lee, Sonali Pandhe, Lei Wang, Juan Hernandez-Doria, Adam M. Spivak, Vicente Planelles, Tianna Petersen, Mamta K. Jain, Elisabeth D. Martinez, Ivan D'Orso
Summary: This study discovered a small molecule activator that alters the state of CD4(+) T cells to promote transcription and reactivation of latent HIV-1 through a unique mechanism of action. The activator triggered oxidative stress and activated a redox-responsive program involving cell-signaling kinases and atypical transcription factors, resulting in changes in viral transcriptional rewiring.
Article
Virology
Riley M. Horvath, Zabrina L. Brumme, Ivan Sadowski
Summary: Mediator kinases CDK8 and CDK19 play a significant role in regulating HIV-1 transcription, and inhibitors of these enzymes may contribute to therapies for latent HIV-1 infection.
JOURNAL OF VIROLOGY
(2023)
Article
Clinical Neurology
Angel Lin, Weam Othman Elbezanti, Alexis Schirling, Adel Ahmed, Rachel Van Duyne, Simon Cocklin, Zachary Klase
Summary: The HIV-1 pandemic poses a significant challenge to the field of medicine, with no cure yet found. Research has identified that the benzodiazepine Alprazolam could be an ideal candidate for latency reversal as it inhibits the transcription factor RUNX1 and increases STAT5 activation, potentially playing a positive role in addressing neuroinflammation associated with neuroHIV-1.
FRONTIERS IN NEUROLOGY
(2021)
Article
Virology
Erich J. Baker, Kelly Hughes, Tatianna Travieso, Mary E. Klotman, Maria Blasi
Summary: Anti-retroviral therapy (ART) has significantly reduced HIV-related morbidity and mortality. However, the long-term persistence of latent viral reservoirs capable of reactivation remains a challenge. This study explores the establishment of HIV-1 latency in renal epithelial cells and finds that current latency reversing agents (LRAs) have limited effectiveness in reactivating HIV-1 in these cells. Further research on LRAs in non-T cells is needed to assess their suitability for a sterilizing cure strategy.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Michelle E. Wong, Chad J. Johnson, Anna C. Hearps, Anthony Jaworowski
Summary: In this study, a robust experimental model was established to quantify and investigate HIV reactivation in latently infected macrophages, showing that different macrophage phenotypes, cellular and tissue environments influence HIV reactivation. Additionally, the study demonstrated that certain latency-reversing agents may have different effects on latently infected macrophages compared to T cells, suggesting the need for dedicated strategies to target these populations in vivo.
JOURNAL OF VIROLOGY
(2021)
Article
Chemistry, Organic
Paul A. Wender, Quang H. Luu-Nguyen, Jack L. Sloane, Alok Ranjan
Summary: We report a one-step generation and reaction of a bifunctional allylating reagent that provides a route for the asymmetric allylation of aldehydes, and an improved Prins macrocyclization strategy.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Mickensone Andre, Madhavan Nair, Andrea D. Raymond
Summary: Antiretrovirals (ARVs) can reduce Human Immunodeficiency Virus (HIV) loads to undetectable levels in infected patients. However, HIV can persist in cellular reservoirs due to certain ARVs' inability to cross anatomical barriers and HIV-1's ability to establish latent infection. Nanomedicine has been used to improve ARV delivery and efficacy in HIV eradication strategies. This review focuses on HIV-1 latency mechanisms and nanomedicine-based approaches for treating HIV.
Article
Immunology
Javier Martinez-Sanz, Sergio Serrano-Villar, Alfonso Muriel, Lucio J. Garcia Fraile, Eva Orviz, Alvaro Mena de Cea, Antoni A. Campins, Santiago Moreno
Summary: This study investigated the metabolic effects of switching from TDF to TAF. The results showed an increase in weight, total cholesterol, and triglycerides after switching to TAF, with no observed increase in obesity or metabolic-related diseases.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Microbiology
Daniela Antunes, Samuel M. Goncalves, Vasiliki Matzaraki, Claudia S. Rodrigues, Relber A. Goncales, Joana Rocha, Jorge Saiz, Antonio Marques, Egidio Torrado, Ricardo Silvestre, Fernando Rodrigues, Frank L. van de Veerdonk, Coral Barbas, Mihai G. Netea, Vinod Kumar, Cristina Cunha, Agostinho Carvalho
Summary: The fungal pathogen Aspergillus fumigatus can cause severe infections in immunocompromised patients. Cellular metabolism plays a crucial role in the immune response to this pathogen. This study highlights the importance of glutamine metabolism in macrophage activation and defense against A. fumigatus. Glutamine metabolism is essential for phagocytosis and cytokine production, and genetic variation in glutamine metabolism genes affects the response to fungal stimulation.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Lorena Carmona-Rodriguez, Aaron S. Gajadhar, Irene Blazquez-Garcia, Laura Guerrero, Manuel A. Fernandez-Rojo, Iker Uriarte, Maricruz Mamani-Huanca, Angeles Lopez-Gonzalvez, Sergio Ciordia, Antonio Ramos, Jose Ignacio Herrero, Maite G. Fernandez-Barrena, Maria Arechederra, Carmen Berasain, Jorge Quiroga, Bruno Sangro, Josepmaria Argemi, Fernando Pardo, Fernando Rotellar, Daniel Lopez, Coral Barbas, Matias A. Avila, Fernando J. Corrales
Summary: The liver is capable of regenerating itself after injury or partial hepatectomy, representing a therapeutic opportunity for liver disease patients. However, the causes of failed liver regeneration are still poorly understood. In this study, the regulation of liver proteome and phosphoproteome after partial hepatectomy was investigated in mice, providing detailed mechanisms of the early phase of liver regeneration. Additionally, the dynamic changes of serum proteome and metabolome in healthy liver transplant donors were analyzed. The results provide insights into the cellular processes orchestrating liver regeneration and may be useful for monitoring the regenerative process and preventing complications associated with liver resection.
Article
Medicine, Research & Experimental
Maria Eugenia Prados, Carmen Navarrete, Adela Garcia-Martin, Isabel Lastres-Cubillo, Francisco Ponce-Diaz, Jose Martinez-Orgado, Eduardo Munoz
Summary: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide, with neuroinflammation and brain-blood barrier (BBB) disruption playing critical roles in its pathogenesis. In this study, the potential therapeutic effects of VCE-005.1, a betulinic acid hydroxamate, were investigated in vitro and in a TBI mouse model. The results demonstrate that VCE-005.1 stabilizes HIF-1 alpha, enhances TJ protein expression, promotes angiogenesis, improves locomotor coordination, preserves BBB integrity, reduces immune cells infiltration, recovers AMPK expression, and decreases neuronal cell apoptosis in the TBI model, highlighting its multitarget anti-inflammatory and neuroprotective properties.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Immunology
Raquel Ron, Elena Moreno, Javier Martinez-Sanz, Fatima Branas, Talia Sainz, Santiago Moreno, Sergio Serrano-Villar
Summary: Studies have shown the significance of CD4/CD8 ratio in monitoring HIV, but there is still debate on its ability to predict adverse outcomes. Some clinical guidelines recommend monitoring it, but knowledge gaps remain on optimal cutoff points, associated clinical events, treatment effects, and decision making improvements.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Virology
Daniel Sepulveda-Crespo, Maria A. Jimenez-Sousa, Amanda Fernandez-Rodiguez, Maria A. Munoz-Fernandez, Jose Luis Jimenez, Santiago Moreno, Felipe Garcia, Isidoro Martinez, Jose M. Benito, Norma Rallon, Salvador Resino
Summary: In this retrospective cohort study, we found a significant association between IRF5-TNPO3 polymorphisms and HIV elite control in long-term nonprogressors (LTNPs). Specifically, certain genotypes and the favorable haplotype of IRF5-TNPO3 were associated with HIV elite control.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemical Research Methods
Miguel Fernandez-Garcia, Ines Mesquita, Carolina Ferreira, Marta Araujo, Bhaskar Saha, Ma Fernanda Rey-Stolle, Antonia Garcia, Ricardo Silvestre, Coral Barbas
Summary: In this study, a multiplatform metabolomics pipeline was used to analyze the metabolome alterations induced in L. donovani-infected human monocyte-derived macrophages at different time points post-infection. The results showed that citrulline, arginine, and glutamine exhibited constant trends across all time points, while most metabolite alterations underwent partial recovery during amastigote maturation. Additionally, an early induction of sphingomyelinase and phospholipase activities, as well as amino acid depletion, was correlated with a major metabolite response. This study provides a comprehensive overview of the metabolome alterations occurring during promastigote-to-amastigote differentiation and maturation of L. donovani inside macrophages, contributing to our understanding of the relationship between L. donovani pathogenesis and metabolic dysregulation.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Medicine, General & Internal
Elena Vazquez-Alejo, Laura Tarancon-Diez, Maria de la Sierra Espinar-Buitrago, Miguel Genebat, Alba Calderon, Guillermo Perez-Cabeza, Esmeralda Magro-Lopez, Manuel Leal, Ma Angeles Munoz-Fernandez
Summary: In hospitalized patients with SARS-CoV-2, immunological activation is reversed during hospitalization but marked exhaustion patterns persist over time. This dysregulation could be a risk factor for reinfection and the development of other pathologies. Additionally, high levels of SARS-CoV-2-specific T-cell response appear to be associated with infection severity.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Miguel Fernandez-Garcia, Manuel Ares-Arroyo, Emilia Wedel, Natalia Montero, Coral Barbas, Ma Fernanda Rey-Stolle, Bruno Gonzalez-Zorn, Antonia Garcia
Summary: This study characterized the endometabolome of H. influenzae Rd KW20 using a multiplatform MS-based metabolomics approach, revealing that current H. influenzae GEMs only capture 15-20% of the endometabolome and showing the interconnection of polar metabolite pools. Additionally, 18 metabolites, including the antimicrobial metabolite cyclo(Leu-Pro), not previously included in H. influenzae GEMs were identified. The study also comprehensively characterized and quantitatively analyzed the phospholipidome of H. influenzae, providing insights into the fatty acyl chain composition and the probability distribution of phospholipids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Correction
Biochemistry & Molecular Biology
Sergio Serrano-Villar, Camilla Tincati, Sajan C. Raju, Johan S. Saenz, Elena Moreno, Rafael Bargiela, Alfonso Cabello-Ubeda, Elena Sendagorta, Alina Kurz, Jose A. Perez A. Molina, Amparo de Benito, Johannes R. Hov, Laura Fernandez-Lopez, Alfonso Muriel, Rosa del Campo, Santiago Moreno, Marius Troseid, Jana Seifert, Manuel Ferrer
Article
Geriatrics & Gerontology
M. S. Espinar-Buitrago, L. Tarancon-Diez, E. Vazquez-Alejo, E. Magro-Lopez, M. Genebat, F. Romero-Candau, M. Leal, M. A. Munoz-Fernandez
Summary: This study investigates the effect of Thymosin-alpha-1 on the immune system of people with different levels of thymic function in SARS-CoV2 infection. The results show that Thymosin-alpha-1 can modulate the activation markers of dendritic cells and decrease the production of proinflammatory cytokines by T cells, improving lymphocyte functionality. Therefore, Thymosin-alpha-1 may have potential benefits in the treatment of COVID-19.
Article
Medicine, General & Internal
Javier Martinez-Sanz, Jorge Diaz-alvarez, Marta Rosas, Raquel Ron, Jose Antonio Iribarren, Enrique Bernal, Felix Gutierrez, Andres Ruiz Sancho, Noemi Cabello, Julian Olalla, Santiago Moreno, Sergio Serrano-Villar
Summary: The study suggests that a low CD4/CD8 ratio during HIV treatment is associated with immunosenescence. Data analysis shows that patients with a CD4/CD8 ratio less than 0.3 in the second year of ART have an increased risk of developing SNAEs in the next five years.
Article
Pediatrics
Anna Turkova, Ellen White, Adeodata R. Kekitiinwa, Vivian Mumbiro, Elizabeth Kaudha, Afaaf Liberty, Grace Miriam Ahimbisibwe, Tumelo Moloantoa, Ussanee Srirompotong, Nozibusiso Rejoice Mosia, Thanyawee Puthanakit, Robin Kobbe, Claudia Fortuny, Hajira Kataike, Dickson Bbuye, Sathaporn Na-Rajsima, Alexandra Coelho, Abbas Lugemwa, Mutsa F. Bwakura-Dangarembizi, Nigel Klein, Hilda A. Mujuru, Cissy Kityo, Mark F. Cotton, Rashida A. Ferrand, Carlo Giaquinto, Pablo Rojo, Avy Violari, Diana M. Gibb, ODYSSEY Trial Team
Summary: This study evaluated the neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment compared to alternative antiretroviral therapy. Numerically, more participants in the dolutegravir group reported psychiatric events and suicidal ideation than those in the standard-of-care group, but these differences should be interpreted cautiously in an open-label trial.
LANCET CHILD & ADOLESCENT HEALTH
(2023)
Article
Multidisciplinary Sciences
Oihane E. Alboniga, Elena Moreno, Javier Martinez-Sanz, Pilar Vizcarra, Raquel Ron, Jorge Diaz-Alvarez, Marta Rosas, Matilde Sanchez-Conde, Juan Carlos Galan, Santiago Angulo, Santiago Moreno, Coral Barbas, Sergio Serrano-Villar
Summary: This study investigates the lipid and metabolite profiles related to SARS-CoV-2 susceptibility and COVID-19 severity. By comparing unvaccinated healthcare workers who remained uninfected with those who became infected, the researchers identified specific lipid profiles that could explain the differences in susceptibility. The findings suggest that an upregulation of certain lipids, such as ceramides and sphingomyelin, may indicate lower susceptibility to SARS-CoV-2 infection.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Erick de la Torre Tarazona, Daniel Jimenez, Daniel Marcos-Mencia, Alejandro Mendieta-Baro, Alejandro Rivera-Delgado, Beatriz Romero-Hernandez, Alfonso Muriel, Mario Rodriguez-Dominguez, Sergio Serrano-Villar, Santiago Moreno
Summary: This study aimed to investigate whether previous infections with human common cold coronaviruses (hCCCoV) might impact susceptibility to and the progression of SARS-CoV-2 infections. The study found that antibody levels against H-CoV-HKU1, H-CoV-229E, and H-CoV-OC43 were associated with mild COVID-19 infections, while antibody levels against H-CoV-NL63 were associated with severe COVID-19 infections.
MICROBIOLOGY RESEARCH
(2023)