Article
Medicine, Research & Experimental
Hekang Du, Meng Kou, Weili Deng, Xueyuan Zhou, Xiaoxiong Zhang, Zhengrong Huang, Bowen Ren, Xingting Cai, Shan Xu, Yu Chen, Lizhu Chen, Chuanben Chen, Hongli Bao, Qi Chen, Daliang Li
Summary: The innate immune system is crucial in combating microbial infection, but abnormal activation of innate immune pathways is a characteristic of various diseases. Therefore, targeted drugs are necessary based on understanding of innate immune signaling pathways. This study showed that a small molecule (DWL-4-140) can selectively regulate STING, resulting in downregulation of DNA-induced interferon responses. DWL-4-140 inhibits the assembly of STING complex and downstream signaling mediators, and it also alleviated lupus in mice. Thus, DWL-4-140 has potential therapeutic applications in autoinflammatory diseases by pharmacologically inhibiting STING.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Prasanta K. Dash, Chen Chen, Rafal Kaminski, Hang Su, Pietro Mancuso, Brady Sillman, Chen Zhang, Shuren Liao, Sruthi Sravanam, Hong Liu, Emiko Waight, Lili Guo, Saumi Mathews, Rahsan Sariyer, R. Lee Mosley, Larisa Y. Poluektova, Maurizio Caocci, Shohreh Amini, Santhi Gorantla, Tricia H. Burdo, Benson Edagwa, Howard E. Gendelman, Kamel Khalili
Summary: Treatment of HIV-1ADA-infected CD34+ NSG-humanized mice with long-acting ester prodrugs of cabotegravir, lamivudine, and abacavir in combination with native rilpivirine followed by dual CRISPR-Cas9 editing of CCR5 and HIV-1 proviral DNA led to elimination of replication-competent virus in 58% of infected mice and restoration of human CD4+ T cell numbers. The dual CRISPR therapy demonstrated statistically significant improvements in HIV-1 cure percentages compared to single treatments. Rating: 9/10
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Chih-Jen Wei, Wei Bu, Laura A. Nguyen, Joseph D. Batchelor, JungHyun Kim, Stefania Pittaluga, James R. Fuller, Hanh Nguyen, Te-Hui Chou, Jeffrey Cohen, Gary J. Nabel
Summary: EBV is a major cause of infectious mononucleosis, human cancers, and multiple sclerosis, with no vaccines or treatments currently available. A nanoparticle vaccine displaying viral glycoproteins was designed to induce potent neutralizing antibodies against EBV and protect against infection in vivo, showing promising results in animal models.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Immunology
Shawn Abeynaike, Silke Paust
Summary: While HIV-1 infection can now be managed with lifelong treatment, complete eradication remains a challenge due to the virus's ability to remain in dormant state in tissue reservoirs and its high mutation rate. Developing a suitable animal model is critical for evaluating pathogenesis and therapeutic approaches for HIV-1 cure strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Gastroenterology & Hepatology
Gulce Sari, Claudia E. Mulders, Jingting Zhu, Gertine W. van Oord, Zongdi Feng, Jolanda J. C. Kreeft-Voermans, Andre Boonstra, Thomas Vanwolleghem
Summary: PegIFN lambda is well tolerated in mice and leads to clearance of a persistent HEV infection in liver-humanized mice. The study found that human liver cells express the IFN lambda receptor and are responsive to pegIFN lambda. Dose escalation studies showed that a dose of 0.3 mg/kg pegIFN lambda treatment resulted in complete clearance of HEV antigen and HEV RNA from the liver in 8 out of 9 liver-humanized mice, demonstrating the potential efficacy of pegIFN lambda in treating chronic HEV infections.
LIVER INTERNATIONAL
(2021)
Article
Biology
Mathieu Amand, Philipp Adams, Rafaela Schober, Gilles Iserentant, Jean-Yves Servais, Michel Moutschen, Carole Seguin-Devaux
Summary: HIV-1 infection leads to inflammasome activation, and inhibiting caspase-1 with VX-765 reduces immune activation, viral load, and HIV-1 reservoir formation. The study showed increased expression of caspase-1, NLRP3, IL-1 beta, IFI16, and AIM2 after HIV-1 infection. Treatment with VX-765 significantly reduced TNF-alpha, IL-18, CD4(+) T cells, viral load, and HIV-1 DNA in the spleen.
Article
Medicine, Research & Experimental
Can M. Sungur, Qiankun Wang, Ayse N. Ozanturk, Hongbo Gao, Aaron J. Schmitz, Marina Cella, Wayne M. Yokoyama, Liang Shan
Summary: The role of NK cells in HIV-1 infections was investigated using a humanized mouse model. The study showed that NK cells directly provided anti-HIV-1 responses in nonlymphoid organs, but had limited functionality in lymphoid organs. Antiretroviral therapy and a broadly neutralizing antibody, PGT121, were found to enhance NK cell function and reduce viral load.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Yuxin Song, Xuan-Nhi Nguyen, Anuj Kumar, Claire da Silva, Lea Picard, Lucie Etienne, Andrea Cimarelli
Summary: This study identifies Trim69 as a negative regulator of various viral infections by regulating the properties of microtubules to limit viral spread. It highlights the importance of the cytoskeleton as an unappreciated battleground in host-pathogen interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Valerie J. Rodriguez-Irizarry, Alina C. Schneider, Daniel Ahle, Justin M. Smith, Edu B. Suarez-Martinez, Ethan A. Salazar, Brianyell McDaniel Mims, Fahmida Rasha, Hanna Moussa, Naima Moustaid-Moussa, Kevin Pruitt, Marcelo Fonseca, Mauricio Henriquez, Matthias A. Clauss, Matthew B. Grisham, Sharilyn Almodovar
Summary: People living with HIV and receiving antiretroviral therapy have improved lifespans. However, persistent viral replication in the lungs can cause chronic inflammation and lead to life-threatening Pulmonary Hypertension (PH). The study of HIV-PH is limited due to a lack of suitable animal models. This study combined HIV with SU5416 or hypoxia in mice with humanized immune systems and found that this combination accurately recapitulates PH, providing a well-suited model for infectious mechanistic pulmonary vascular research in small animals.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Immacolata Prevenzano, Alessia Leone, Michele Longo, Antonella Nicolo, Serena Cabaro, Francesca Collina, Iacopo Panarese, Gerardo Botti, Pietro Formisano, Raffaele Napoli, Francesco Beguinot, Claudia Miele, Cecilia Nigro
Summary: Tight control of glycemia is crucial for treating type 2 diabetes mellitus (T2DM), but factors other than poor glycemic control may also contribute to the progression of T2DM. This study reveals that increased levels of methylglyoxal (MGO) can impair glucose tolerance and insulin secretion in mice lacking glyoxalase 1 (Glo1KD), leading to early phenotypes associated with T2DM progression. Furthermore, MGO-induced beta-cell dysfunction can be reversed by senolytic treatment. These findings suggest that targeting MGO accumulation could be a potential approach for preventing T2DM.
Article
Pharmacology & Pharmacy
Delma Veron, Pardeep K. Aggarwal, Qi Li, Gilbert Moeckel, Michael Kashgarian, Alda Tufro
Summary: Vascular endothelial growth factor-a (VEGF-A) and nitric oxide (NO) play crucial roles in maintaining the homeostasis of the glomerular filtration barrier, and their dysregulation is observed in diabetic kidney disease (DKD). In this study, the authors investigated the effects of inducible podocyte VEGF-A knockdown (VEGF(KD)) in diabetic mice and endothelial nitric oxide synthase knockout mice (eNOS(-/-)). The findings showed that podocyte VEGF-A and eNOS deficiency resulted in diffuse glomerulosclerosis in mice, and compensatory NO and thiol generation prevented severe proteinuria and glomerular filtration rate (GFR) loss in VEGF(KD) diabetic mice with intact eNOS. On the other hand, induction of VEGF(KD) in eNOS(-/-):VEGF(KD) mice led to massive proteinuria and renal failure, resembling DKD in the absence of diabetes. The study also identified abnormal S-nitrosylation of certain proteins as a potential mechanism underlying the development of advanced glomerulosclerosis and renal failure.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Jacqueline M. Brady, Meredith Phelps, Scott W. MacDonald, Evan C. Lam, Adam Nitido, Dylan Parsons, Christine L. Boutros, Cailin E. Deal, Wilfredo F. Garcia-Beltran, Serah Tanno, Harini Natarajan, Margaret E. Ackerman, Vladimir D. Vrbanac, Alejandro B. Balazs
Summary: This study investigates the efficacy and relative contribution of HIV antibodies using a humanized mouse model. The findings suggest that antibodies lacking Fc-mediated functionality have reduced protection against HIV transmission, while highly functional antibodies can provide significant protection against infection.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biology
Ting Guo, Qi Deng, Zhipeng Qiu, Libin Rong
Summary: Despite years of cART, HIV persists and rebounds in infected individuals, and the sources contributing to viral persistence and rebound are not fully understood. This study used HIV infection models to fit viral load data in treated and untreated humanized mice, and found that the loss of infected CD4+ T cells and macrophages contributes to viral decay, and latent infection of CD4+ T cells may cause the last phase of viral decay. Furthermore, the study suggests that pre-ART viral load and latent reservoir size can affect viral growth rate and predict the time to rebound, and early and prolonged cART can delay viral rebound after treatment cessation.
JOURNAL OF THEORETICAL BIOLOGY
(2023)
Article
Virology
Gulce Sari, Jingting Zhu, Charuta Ambardekar, Xin Yin, Andre Boonstra, Zongdi Feng, Thomas Vanwolleghem
Summary: ORF3 plays a crucial role in HEV release and persistent infection, as its absence significantly decreases HEV replication and virion release. Our findings provide a rationale for targeting ORF3 as a treatment strategy for HEV infection.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Matthew T. Ollerton, Joy M. Folkvord, Kristina K. Peachman, Soumya Shashikumar, Elaine B. Morrison, Linda L. Jagodzinski, Sheila A. Peel, Mohammad Khreiss, Richard T. D'Aquila, Sofia Casares, Mangala Rao, Elizabeth Connick
Summary: Humanized DRAGA mice can generate virus-specific antibodies in HIV-1 infection, but their support for germinal center responses is limited.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Jeffrey Lian, Aleksandra J. Ozga, Caroline L. Sokol, Andrew D. Luster
Article
Microbiology
Yahui Guo, Shinji Kasahara, Anupam Jhingran, Nicholas L. Tosini, Bing Zhai, Mariano A. Aufiero, Kathleen A. M. Mills, Mergim Gjonbalaj, Vanessa Espinosa, Amariliz Rivera, Andrew D. Luster, Tobias M. Hohl
CELL HOST & MICROBE
(2020)
Article
Immunology
Rod A. Rahimi, Keshav Nepal, Murat Cetinbas, Ruslan Sadreyev, Andrew D. Luster
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Editorial Material
Immunology
Rod A. Rahimi, Andrew D. Luster
TRENDS IN IMMUNOLOGY
(2020)
Article
Multidisciplinary Sciences
Ramya Sivangala Thandi, Rajesh Kumar Radhakrishnan, Deepak Tripathi, Padmaja Paidipally, Abul K. Azad, Larry S. Schlesinger, Buka Samten, Sachin Mulik, Ramakrishna Vankayalapati
NATURE COMMUNICATIONS
(2020)
Article
Oncology
Dexter P. Mendoza, Puja Kohli, John W. Nance, Ramandeep Singh, Josalyn Cho, Jason Griffith, R. Scott Harris, Vanessa J. Kelly, Andrew D. Luster, Benjamin Medoff, Subba R. Digumarthy
ANNALS OF TRANSLATIONAL MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Shiva Keshava, Jhansi Magisetty, Torry A. Tucker, Weshely Kujur, Sachin Mulik, Charles T. Esmon, Steven Idell, L. Vijaya Mohan Rao, Usha R. Pendurthi
Summary: EPCR plays a critical role in the pathogenesis of pleural thickening and fibrosis induced by S. pneumoniae infection. Deficiency of EPCR offers protection against lung function impairment and pleural remodeling caused by S. pneumoniae infection.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yersultan Mirasbekov, Adina Zhumakhanova, Almira Zhantuyakova, Kuanysh Sarkytbayev, Dmitry Malashenkov, Assel Baishulakova, Veronika Dashkova, Thomas A. Davidson, Ivan A. Vorobjev, Erik Jeppesen, Natasha S. Barteneva
Summary: The study effectively utilized machine learning techniques to detect and quantify colonial morphospecies of Microcystis algae. Results demonstrate the method's efficiency in evaluating changes in colonial microalgae, with potential applications in research.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Dmitry Malashenkov, Veronika Dashkova, Kymbat Zhakupova, Ivan A. Vorobjev, Natasha S. Barteneva
Summary: In this study, phytoplankton assemblages in two lakes were analyzed using traditional morphological and next-generation sequencing methods. The findings suggest limitations of NGS in identifying phytoplankton taxa, but combining it with microscopy allows for a complete taxonomic characterization. The integrated morphological and molecular approach shows promise in understanding aquatic ecosystem organization processes.
SCIENTIFIC REPORTS
(2021)
Article
Environmental Sciences
Yersultan Mirasbekov, Aigerim Abdimanova, Kuanysh Sarkytbayev, Kanat Samarkhanov, Aidyn Abilkas, Daria Potashnikova, Galina Arbuz, Zhanpeis Issayev, Ivan A. Vorobjev, Dmitry Malashenkov, Natasha S. Barteneva
Summary: Algal blooms are common in freshwater bodies worldwide, often resulting in fish kills. A study conducted along the Ural River in 2018-2019 identified various potentially toxic phytoplankton species, with dominant species including Cuspidothrix issatschenkoi, Dolichospermum cf. flos-aquae, and Pseudanabaena limnetica. Molecular phylogenetic investigations and gene sequencing revealed the presence of toxin-producing cyanobacteria, which could pose a threat to aquaculture in the region.
FRONTIERS IN MARINE SCIENCE
(2021)
Article
Multidisciplinary Sciences
Sumit Sen Santara, Angela C. Crespo, Sachin Mulik, Cristian Ovies, Selma Boulenouar, Jack L. Strominger, Judy Lieberman
Summary: Zika virus infection during pregnancy can lead to placental damage and fetal birth defects, with limited understanding of the cellular immune response at the maternal-fetal interface. Research has shown that dNK cells in the first trimester are able to kill Zika virus-infected trophoblasts, indicating that certain immune cells protect the fetus by eliminating infected cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cardiac & Cardiovascular Systems
Polina Len, Gaukhar Iskakova, Zarina Sautbayeva, Aigul Kussanova, Ainur T. Tauekelova, Madina M. Sugralimova, Anar S. Dautbaeva, Meruert M. Abdieva, Eugene D. Ponomarev, Alexander Tikhonov, Makhabbat S. Bekbossynova, Natasha S. Barteneva
Summary: This study examined the association between coagulation parameters and COVID-19 infection severity through a meta-analysis. The results showed that most coagulation parameters, except for platelets, were significantly elevated in patients with severe COVID-19. D-dimers and fibrinogen levels were found to have the strongest association with disease severity.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Microbiology
Veronika Dashkova, Dmitry Malashenkov, Assel Baishulakova, Thomas A. Davidson, Ivan A. Vorobjev, Erik Jeppesen, Natasha S. Barteneva
Summary: This study explores the effects of temperature and nutrient enrichment on phytoplankton communities in shallow lakes. It finds that nitrogen enrichment leads to a shift in dominance from cyanobacteria to a mix of cyanobacteria and green algae. Additionally, high temperatures stimulate phytoplankton size increase, while low temperatures result in size decrease. The combination of high temperature and nitrogen enrichment leads to the lowest phytoplankton diversity.
Review
Microbiology
Natasha S. Barteneva, Ayagoz Meirkhanova, Dmitry Malashenkov, Ivan A. Vorobjev
Summary: Regulated cell death plays a crucial role in the development and functionality of multicellular organisms. Recent evidence suggests that regulated cell death is a universal phenomenon across all domains of life. Cyanobacteria are of particular interest due to their significance in aquatic and terrestrial habitats and their role as primary producers in global nutrient cycling. However, our current understanding of cyanobacterial regulated cell death is still limited, relying mainly on biochemical and morphological observations. This review focuses on discussing the functional implications of regulated cell death in cyanobacterial communities.
Review
Food Science & Technology
Galina Nugumanova, Eugene D. Ponomarev, Sholpan Askarova, Elizaveta Fasler-Kan, Natasha S. Barteneva
Summary: Cyanobacteria produce a variety of cyanotoxins and cyanopeptides that have both acute and long-term neurotoxic effects. These compounds can block proteins and channels, inhibit essential enzymes, and cause mistranslation of proteins, leading to neuronal death and neurodegeneration. The production of cyanopeptides and non-canonical amino acids is an ancient mechanism that may disrupt gut microorganisms and affect mitochondrial function in neurons. Understanding this interaction is crucial for targeting or preventing neurodegenerative diseases.
