Article
Oncology
Harald Krenzlin, Mykola Zdioruk, Michal O. Nowicki, Tomer Finkelberg, Naureen Keric, Niels Lemmermann, Magdalena Skubal, E. Antonio Chiocca, Charles H. Cook, Sean E. Lawler
Summary: The study suggests that the CMV-induced upregulation of c-MET may be a potential mechanism involved in the effects of CMV on GBM growth.
Article
Biology
Philipp Kolb, Katja Hoffmann, Annika Sievert, Henrike Reinhard, Eva Merce-Maldonado, Vu Thuy Khanh Le-Trilling, Anne Halenius, Dominique Guetle, Hartmut Hengel
Summary: HCMV uses multiple immune evasion strategies to counteract host immune control mechanisms, including the simultaneous expression of gp34 and gp68 to efficiently antagonize host FcγR activation through distinct but synergizing mechanisms. Gp34 enhances immune complex internalization, while gp68 inhibits host FcγR binding to immune complexes.
Article
Immunology
WenJun Liu, DanLei Huang, YuJing Liu, HongYu He, ZhunYong Gu, YiMei Liu, QingNan Yang, Zhe Luo, MinJie Ju
Summary: Background: This study investigated the role of cyclic helix B peptide (CHBP) in sepsis-induced injury. The results showed that CHBP improved sepsis-induced injury by reducing the permeability of human pulmonary microvascular endothelial cells (HPMECs) and suppressing NF-kappa B signaling and inflammation.
CLINICAL IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yujie Ren, An Wang, Bowen Zhang, Wenting Ji, Xiao-Xu Zhu, Jing Lou, Muhan Huang, Yang Qiu, Xi Zhou
Summary: UL36 encoded by human cytomegalovirus not only inhibits apoptosis but also suppresses immune signaling by targeting IRF3 directly. Although UL36-mediated inhibition of apoptosis enhances immune signaling, its immunosuppressive activity counterbalances this effect.
Article
Biochemistry & Molecular Biology
Mi-Jeong Kim, Ji Young Kim, Ji Hye Shin, Yeeun Kang, Ji Su Lee, Juhee Son, Soo-Kyung Jeong, Daesik Kim, Duk-Hwan Kim, Eunyoung Chun, Ki-Young Lee
Summary: This study investigates the crosstalk between FFARs and TLRs in lung cancer progression. The results show that FFAR2 is down-regulated in lung cancer and negatively correlated with TLR2 and TLR3. Functionally, stimulation of FFAR2 inhibits migration, invasion, and colony formation induced by TLR2 and TLR3 through the cAMP-AMPK-TAK1 signaling axis. Thus, FFAR2 agonists might be potential therapeutic agents for lung cancer.
CELL AND BIOSCIENCE
(2023)
Article
Cell Biology
Erna Marija Meskyte, Laura Pezze, Laura Bartolomei, Mattia Forcato, Irene Adelaide Bocci, Giovanni Bertalot, Mattia Barbareschi, Leticia Oliveira-Ferrer, Alessandra Bisio, Silvio Bicciato, Daiva Baltriukiene, Yari Ciribilli
Summary: The oncoprotein ETV7 is up-regulated in all types of breast cancer and promotes cancer progression by increasing cell proliferation and stemness. In this study, it was found that ETV7 plays a role in breast cancer inflammation by suppressing innate immune and inflammatory responses. The down-regulation of TNFRSF1A by ETV7 reduces NF-kappa B signaling activation and there is a potential crosstalk between ETV7 and STAT3, resulting in the repression of TNFRSF1A transcription.
CELL DEATH & DISEASE
(2023)
Article
Immunology
Jian Hu, Xue Wang, Xiongjian Chen, Yani Fang, Kun Chen, Wenshuo Peng, Zhengyi Wang, Kaiming Guo, Xianxi Tan, Fei Liang, Li Lin, Ye Xiong
Summary: The study found that hydroxychloroquine (HCQ) can improve neurological recovery in mice post-TBI by inhibiting the inflammatory response through the TLR4/NF-kappa B signaling pathway. HCQ reduces the expression of proinflammatory cytokines, attenuates blood-brain barrier (BBB) disruption and brain edema, and upregulates tight junction expression. This suggests that HCQ could be a potential therapeutic agent for TBI treatment.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Multidisciplinary Sciences
Raghuram Koganti, Tejabhiram Yadavalli, Yogesh Sutar, Sudipta Mallick, Abhijit Date, Deepak Shukla
Summary: The aromatic fatty acid phenylbutyrate (PBA) has been found to exhibit potent anti-inflammatory effects in the treatment of corneal inflammation. It accelerates the resolution of inflammation and promotes corneal healing by inhibiting NF-kappa B signaling in a mouse model of ocular inflammation. Furthermore, PBA can synergize with dexamethasone to antagonize NF-kappa B signaling at lower drug concentrations.
Review
Biochemistry & Molecular Biology
Thomas D. Gilmore
Summary: NF-kappa B is extensively studied for its roles in cancer development and is often constitutively or aberrantly activated in human cancers. Activation can occur due to mutations in NF-kappa B factors, upstream regulators, or pathways impacting NF-kappa B. Despite being considered an anticancer strategy, inhibition of NF-kappa B has had limited success in cancer treatment.
Article
Biology
Nicholas Sim, Yinghui Li
Summary: p52-induced ETS1 overexpression in glioma cells remodels the genome-wide regulatory network of p52 and ETS1 to transcriptionally drive cancer progression. Chronic inflammation promotes glioma progression by activating NF-kappa B signalling, which promotes cancer cell invasion and angiogenesis. Non-canonical NF-kappa B activation directly regulates p52 at the ETS1 promoter, leading to its overexpression and impacting the genomic landscape of ETS1 in a glioma-specific manner.
COMMUNICATIONS BIOLOGY
(2023)
Article
Orthopedics
Huan Wang, Weidong Zhang, Yan Cai, Qianping Guo, Liangbin Pan, Genglei Chu, Jianquan Chen, Zhangqin Yuan, Bin Li
Summary: This study found that moderate mechanical stimulation can regulate the inflammatory response of annulus fibrosus cells through the YAP signaling pathway, which in turn affects intervertebral disc degeneration and low back pain. Moderate mechanical stimulation can inhibit the inflammatory response and promote cell growth, making it a potential therapeutic approach for the prevention and treatment of disc degeneration.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ruigong Zhu, Xian Ji, Xuan Wu, Jiajing Chen, Xuesong Li, Hong Jiang, Haiping Fu, Hui Wang, Zhe Lin, Xin Tang, Shixiu Sun, Qingguo Li, Bingjian Wang, Hongshan Chen
Summary: Cellular senescence is closely associated with age-related diseases, and ovarian aging serves as the pathophysiological foundation of reproductive system diseases. By investigating the protective role of melatonin in human ovarian surface epithelial cells, it was found that melatonin can antagonize oncogene-induced senescence by inhibiting the ROS-YTHDF2-MAPK-NF-kappa B pathway. These findings provide insights into potential strategies for preventing and treating ovarian aging.
Article
Biochemistry & Molecular Biology
Fan Li, Cong Yin, Zewei Ma, Kelin Yang, Lijuan Sun, Chen Duan, Tao Wang, Abdelaziz Hussein, Lina Wang, Xiaotong Zhu, Ping Gao, Qianyun Xi, Yongliang Zhang, Gang Shu, Songbo Wang, Qingyan Jiang
Summary: The study suggests that PHD3 may affect protein turnover in muscle tissue by mediating the inflammatory NF-kappa B signal pathway, and the increased expression of PHD3 in denervated muscle could be an important regulator in inducing muscle atrophy.
Article
Biochemistry & Molecular Biology
Matthew Biancalana, Eviatar Natan, Michael J. Lenardo, Alan R. Fersht
Summary: The study reveals that the p50 and p65 Rel subunits in the NF-kappa B complex exhibit different kinetic stability, with a strong preference for the formation of the p50/p65 heterodimer over homodimers. This suggests that cells can modulate NF-kappa B activity by fine-tuning the relative proportions of p50 and p65 proteins and their expression time.
Article
Immunology
Yunfei Wang, Kaikai Yi, Xing Liu, Yanli Tan, Weili Jin, Yansheng Li, Junhu Zhou, Hongjun Wang, Chunsheng Kang
Summary: HOTAIR activates NF-kappa B pathway in glioma cells, promoting inflammatory signaling and immune escape.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Wenjuan Dong, Heather Mead, Lei Tian, Jun-Gyu Park, Juan Garcia, Sierra Jaramillo, Tasha Barr, Daniel S. Kollath, Vanessa K. Coyne, Nathan E. Stone, Ashley Jones, Jianying Zhang, Aimin Li, Li-Shu Wang, Martha Milanes-Yearsley, Jordi B. Torrelles, Luis Martinez-Sobrido, Paul S. Keim, Bridget Marie Barker, Michael A. Caligiuri, Jianhua Yu
Summary: The K18-hACE2 mouse model provides a comprehensive analysis of SARS-CoV-2 infection and shows that different viral doses lead to varying degrees of organ damage. This model accurately reproduces both severe and non-severe COVID-19 in humans, making it valuable for drug development.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Ting Y. Wong, Alexander M. Horspool, Brynnan P. Russ, Chengjin Ye, Katherine S. Lee, Michael T. Winters, Justin R. Bevere, Olivia A. Miller, Nathaniel A. Rader, Melissa Cooper, Theodore Kieffer, Julien Sourimant, Alexander L. Greninger, Richard K. Plemper, James Denvir, Holly A. Cyphert, Mariette Barbier, Jordi B. Torrelles, Ivan Martinez, Luis Martinez-Sobrido, F. Heath Damron
Summary: SARS-CoV-2 variants of concern (VoC) have enhanced immune evasion, as demonstrated in this study using passive immunization with human convalescent plasma (HCP). The efficacy of HCP generated to ancestral SARS-CoV-2 was tested against the Alpha, Beta, and Delta VoC in a mouse model. The results show that HCP was unable to control the lethality of these VoC strains, highlighting the need for in vivo models to evaluate emerging strains' immune evasion.
JOURNAL OF VIROLOGY
(2022)
Review
Multidisciplinary Sciences
Julien Sourimant, Carolin M. Lieber, Megha Aggarwal, Robert M. Cox, Josef D. Wolf, Jeong-Joong Yoon, Mart Toots, Chengin Ye, Zachary Sticher, Alexander A. Kolykhalov, Luis Martinez-Sobrido, Gregory R. Bluemling, Michael G. Natchus, George R. Painter, Richard K. Plemper
Summary: This study describes a drug called 4'-fluorouridine (4'-FlU), which has broad-spectrum antiviral effects and potential for the treatment of respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and related RNA virus infections. In vitro and in vivo experiments showed that 4'-FlU inhibited RSV, SARS-CoV-2, and related RNA viruses with high efficacy, making it a promising candidate for broad-spectrum therapeutics against respiratory viruses.
Article
Physiology
Rachel Warren, Andrew M. Dylag, Molly Behan, William Domm, Min Yee, Margot Mayer-Proschel, Luis Martinez-Sobrido, Michael A. O'Reilly
Summary: Children and young adults with mutant forms of the ATM gene, which is involved in DNA damage signaling and mitochondrial homeostasis, suffer from respiratory infections, immune deficiencies, and obstructive airways disease associated with disorganized airway epithelium. A study on mice showed that ATM is required for the regeneration of injured airway epithelium after influenza virus infection. Mice lacking ATM exhibited increased airway resistance and reduced lung compliance during infection, and their lungs developed an abnormal proximal airway epithelium containing cells lacking expression of the immunomodulatory protein Scgb1a1. Restoration of Scgb1a1 expression in the airways required ATM and failure to efficiently restore it may contribute to the respiratory diseases seen in individuals with ataxia telangiectasia.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Review
Medical Laboratory Technology
Kin Israel Notarte, Abbygail Therese Ver, Jacqueline Veronica Velasco, Adriel Pastrana, Jesus Alfonso Catahay, Gian Luca Salvagno, Eric Peng Huat Yap, Luis Martinez-Sobrido, Jordi B. Torrelles, Giuseppe Lippi, Brandon Michael Henry
Summary: This paper investigates the effects of age, sex, serostatus, and comorbidities on humoral response after mRNA-based Pfizer-BioNTech vaccination. The findings suggest that older individuals, males, seronegative individuals, and those with more comorbidities have a weaker humoral immune response.
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES
(2022)
Review
Virology
Kin Israel Notarte, Israel Guerrero-Arguero, Jacqueline Veronica Velasco, Abbygail Therese Ver, Maria Helena Santos de Oliveira, Jesus Alfonso Catahay, Md Siddiqur Rahman Khan, Adriel Pastrana, Grzegorz Juszczyk, Jordi B. Torrelles, Giuseppe Lippi, Luis Martinez-Sobrido, Brandon Michael Henry
Summary: This review examines the decline in efficacy of mRNA vaccines for COVID-19 in preventing breakthrough infections due to diminishing humoral immunity over time. The study finds that the peak humoral response is reached 21-28 days after the second dose, after which antibody levels progressively decline at 4-6 months post-vaccination. Regardless of patient-related factors, antibody levels show a decline in both anti-receptor binding domain IgG and anti-spike IgG. The study highlights the need for more efficient vaccination strategies to combat waning immunity.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Microbiology
Maria M. Lorenzo, Aitor Nogales, Kevin Chiem, Rafael Blasco, Luis Martinez-Sobrido
Summary: This study demonstrates that poxviruses can be effectively attenuated by synonymous codon deoptimization, providing a new approach for the development of attenuated vaccines for the treatment of poxvirus infection.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Rena A. Mizrahi, Wendy Y. Lin, Ashley Gras, Ariel R. Niedecken, Ellen K. Wagner, Sheila M. Keating, Nikita Ikon, Vishal A. Manickam, Michael A. Asensio, Jackson Leong, Angelica Medina-Cucurella, Emily Benzie, Kyle P. Carter, Yao Chiang, Robert C. Edgar, Renee Leong, Yoong Wearn Lim, Jan Fredrik Simons, Matthew J. Spindler, Kacy Stadtmiller, Nicholas Wayham, Dirk Buscher, Jose Vicente Terencio, Clara Di Germanio, Steven M. Chamow, Charles Olson, Paula A. Pino, Jun-Gyu Park, Amberlee Hicks, Chengjin Ye, Andreu Garcia-Vilanova, Luis Martinez-Sobrido, Jordi B. Torrelles, David S. Johnson, Adam S. Adler
Summary: This study successfully generated a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 using microfluidics, flow sorting, and a targeted integration cell line. The drug was manufactured consistently at the clinical scale and offers a new approach to treating infectious diseases by targeting multiple epitopes of the virus.
Article
Multidisciplinary Sciences
Isreal Moreno, Irene Rodriguez-Sanchez, Xenia Schafer, Joshua Munger
Summary: HCMV infection induces the expression of a tissue atypical neuronal glycolytic enzyme, activating glycolysis and UDP-sugar metabolism, increasing the accumulation of glycosyl building blocks, and enabling the expression of an essential viral glycoprotein and the production of infectious virions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Maria M. Lorenzo, Alejandro Marin-Lopez, Kevin Chiem, Luis Jimenez-Cabello, Irfan Ullah, Sergio Utrilla-Trigo, Eva Calvo-Pinilla, Gema Lorenzo, Sandra Moreno, Chengjin Ye, Jun-Gyu Park, Alejandro Matia, Alejandro Brun, Juana M. Sanchez-Puig, Aitor Nogales, Walther Mothes, Pradeep D. Uchil, Priti Kumar, Javier Ortego, Erol Fikrig, Luis Martinez-Sobrido, Rafael Blasco
Summary: The COVID-19 pandemic highlights the need for fast responses and reliable technologies for vaccine development. This study reports on the construction and preclinical testing of a recombinant MVA vaccine, with the MVA-Spf vaccine candidate showing higher levels of antibodies, a stronger T cell response, and a higher degree of protection.
Article
Microbiology
Michael Piepenbrink, Fatai Oladunni, Aitor Nogales, Ahmed M. Khalil, Theresa Fitzgerald, Madhubanti Basu, Christopher Fucile, David J. Topham, Alexander F. Rosenberg, Luis Martinez-Sobrido, James J. Kobie
Summary: Influenza A virus (IAV) infections pose a significant threat to public health due to the variable nature of the virus. This study shows that immunization with a seasonal inactivated influenza vaccine (IIV) can increase the levels of antibodies against H3N2 IAV, a strain known for its genetic drift. These antibodies have broad and potent antiviral activity and can protect against various H3N2 IAV strains. They also persist in the bone marrow, indicating their potential for long-term immunity. These findings contribute to the development of a universal influenza vaccine.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Kevin Chiem, Aitor Nogales, Maria Lorenzo, Desarey Morales Vasquez, Yan Xiang, Yogesh K. Gupta, Rafael Blasco, Juan Carlos de la Torre, Luis Martinez-Sobrido
Summary: Despite the eradication of smallpox, some orthopoxviruses, such as monkeypox virus (MPXV), remain important human pathogens. Vaccines for smallpox are effective against MPXV, but limited in access. Current antiviral treatments for MPXV are limited to two FDA-approved drugs. Therefore, there is an urgent need to discover novel antivirals for the treatment of MPXV and other potentially zoonotic orthopoxvirus infections. Here, we found 13 compounds that inhibit both VACV and MPXV, derived from two different libraries of compounds known to inhibit various RNA viruses.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Luis Martinez-Sobrido, James J. Kobie
Article
Virology
Ahmed M. Khalil, Michael S. Piepenbrink, Ian Markham, Madhubanti Basu, Luis Martinez-Sobrido, James J. Kobie
Summary: IBV contributes significantly to morbidity and mortality, particularly in children, necessitating improvements in vaccines and treatments. A specific hMAb, 1092D4, has been found to have minimal dependence on Fc-effector functions for in vivo antiviral activity.
Review
Immunology
Ahlam Alasiri, Raya Soltane, Akram Hegazy, Ahmed Magdy Khalil, Sara H. Mahmoud, Ahmed A. Khalil, Luis Martinez-Sobrido, Ahmed Mostafa
Summary: Despite being widespread in wild birds and domestic poultry, human infections with highly pathogenic avian influenza H5Nx viruses have been limited since 1996. Few countries use vaccination as a control strategy, while most rely on culling infected flocks. China and Egypt are the major sites where vaccination has been employed, particularly for clade 2.3.4.4b H5N1 viruses. However, improper implementation of control strategies in Egypt has resulted in continuous outbreaks and virus evolution. Comprehensive surveillance in endemic areas is crucial to understand the public health risk of newly emerging immune-evasive or drug-resistant H5Nx variants.