Article
Multidisciplinary Sciences
Yoshitaka Kase, Tsukika Sato, Yuji Okano, Hideyuki Okano
Summary: The GADD45G gene promotes neurite outgrowth in human neurons by facilitating microtubule polymerization through the p38 MAPK/CDC25B signaling pathway. It is highly expressed in developing human cerebral specimens.
Review
Chemistry, Medicinal
Corrado Pelaia, Alessandro Vatrella, Luca Gallelli, Nicola Lombardo, Angela Sciacqua, Rocco Savino, Girolamo Pelaia
Summary: The p38 MAPK subgroup plays a crucial role in the pathogenesis of asthma and COPD by regulating the expression of various inflammatory mediators and fibrogenic factors. Studies suggest that p38 MAPK may be a potential therapeutic target, with research evaluating its effects in both asthma and COPD treatment.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Review
Cell Biology
Ali Ahmadi, Sajjad Ahrari, Jafar Salimian, Zahra Salehi, Mehrdad Karimi, Alireza Emamvirdizadeh, Sadegh Azimzadeh Jamalkandi, Mostafa Ghanei
Summary: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation caused by airway and/or alveolar remodeling. Maladjusted and self-reinforcing immune responses play a significant role in the development and progression of COPD. Targeting the p38 isoforms, which regulate immune and inflammatory responses, has shown therapeutic potential in COPD. However, clinical trials testing various p38 inhibitors have produced mixed results, and further research is needed to develop more effective therapies for COPD.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Pharmacology & Pharmacy
Nathalia Grave, Thamiris Becker Scheffel, Fernanda Fernandes Cruz, Liliana Rockenbach, Marcia Ines Goettert, Stefan Laufer, Fernanda Bueno Morrone
Summary: Gliomas are debilitating malignant brain tumors with limited response to therapies, driven by molecular abnormalities like mutations in regulatory networks. The MAPK pathway, particularly p38 MAPK activation, plays a crucial role in glioma cell invasion and metastasis, and is associated with tumor grade and chemotherapy resistance, underlining its potential as a therapeutic target.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Salome Ruiz-Demoulin, Eva Trenquier, Sanaa Dekkar, Sebastien Deshayes, Prisca Boisguerin, Cesar Serrano, Pascal de Santa Barbara, Sandrine Faure
Summary: Gastrointestinal stromal tumor (GIST) is mainly caused by a KIT receptor tyrosine kinase oncogenic mutation. Targeting KIT using tyrosine kinase inhibitors provides benefit, but resistance eventually develops. This study shows that LIX1 is upregulated in response to imatinib or sunitinib treatment in GIST cells and silencing LIX1 enhances the anti-tumor effect of imatinib by inhibiting MAPK signaling reactivation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Ja-Rang Lee, Se-Hee Choe, Young-Hyun Kim, Hyeon-Mu Cho, Hye-Ri Park, Hee-Eun Lee, Yeung Bae Jin, Ji-Su Kim, Kang Jin Jeong, Sang-Je Park, Jae-Won Huh
Summary: This study identified differentially expressed genes related to aging in African green monkeys, with a focus on genes associated with protein synthesis. These findings provide potential targets for aging treatment research.
Article
Biochemistry & Molecular Biology
Roberto Romeo, Salvatore Giofre, Maria A. Chiacchio, Lucia Veltri, Consuelo Celesti, Daniela Iannazzo
Summary: A series of novel potential inhibitors of p38 MAPK have been synthesized, with some compounds showing good inhibitory activity in biological assays. Molecular modeling data confirmed the designed compounds have a reasonable binding mode and good binding affinity in the ATP binding pocket of p38 alpha kinase.
Article
Oncology
Li-Ting Wang, Kwei-Yan Liu, Shyh-Shin Chiou, Shau-Ku Huang, Shih-Hsien Hsu, Shen-Nien Wang
Summary: The study revealed that ERK1 phosphorylates ISX leading to its nuclear translocation and downstream oncogenic signaling in hepatocellular carcinoma (HCC). The co-expression of ERK1 and ISX in HCC samples suggests their potential as prognostic and therapeutic targets in HCC.
Article
Immunology
Celeste Coleman, Lara A. Doyle-Meyers, Kasi E. Russell-Lodrigue, Nadia Golden, Breanna Threeton, Kejing Song, Genevieve Pierre, Carl Baribault, Rudolf P. Bohm, Nicholas J. Maness, Jay K. Kolls, Jay Rappaport, Joseph C. Mudd
Summary: Understanding immune responses to SARS-CoV-2 infection is crucial for vaccine and treatment development. This study analyzed blood transcriptome profiles at different timepoints in monkeys infected with SARS-CoV-2, revealing coordinated transcriptional changes early in infection. Pathway analysis showed regulation of interferon-stimulated genes and differences in neutrophil response between monkey species.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jared Pitts, Darius Babusis, Meghan S. Vermillion, Raju Subramanian, Kim Barrett, Diane Lye, Bin Ma, Xiaofeng Zhao, Nicholas Riola, Xuping Xie, Adriana Kajon, Xianghan Lu, Roy Bannister, Pei-Yong Shi, Maria Toteva, Danielle P. Porter, Bill J. Smith, Tomas Cihlar, Richard Mackman, John P. Bilello
Summary: The study found that GS-441524 is metabolized less efficiently than RDV in human alveolar and bronchial primary cells, leading to lower in vitro SARS-CoV-2 antiviral activity. Oral dosing of GS-441524 in African green monkeys resulted in low plasma levels due to limited bioavailability, while intravenous administration of GS-441524 led to higher plasma concentrations but lower lung levels compared to IV RDV. Daily IV treatment with GS-441524 showed dose-dependent efficacy in reducing SARS-CoV-2 replication in the lower respiratory tract of infected animals.
ANTIVIRAL RESEARCH
(2022)
Article
Virology
Lori A. Rowe, Brandon J. Beddingfield, Kelly Goff, Stephanie Z. Killeen, Nicole R. Chirichella, Alexandra Melton, Chad J. Roy, Nicholas J. Maness
Summary: In recent months, new variants of SARS-CoV-2 that are more transmissible and can escape host immunity have emerged. Little is known about the evolution of SARS-CoV-2 in nonhuman primate models. This study sequenced viral RNA from rectal swabs of African green monkeys infected with SARS-CoV-2. Two distinct patterns of viral evolution were identified, and the importance of the furin cleavage site for in vivo infection was confirmed.
Review
Chemistry, Medicinal
Mehdi Valipour
Summary: The aim of this study is to evaluate the therapeutic potential of tanshinone IIA and pinocembrin for the treatment of central nervous system complications of COVID-19. Through a review of published studies, tanshinone IIA and pinocembrin were found to have the ability to penetrate the CNS. The study concludes that tanshinone IIA and pinocembrin have great potential for better treatment of these complications and should be further evaluated in high-quality clinical trials.
PHYTOTHERAPY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Saleem Iqbal, Raju Potharaju, S. Naveen, N. K. Lokanath, Arasambattu K. Mohanakrishnan, Krishnasamy Gunasekaran
Summary: Alzheimer's disease is characterized by the accumulation of misfolded proteins, leading to neuronal degeneration and cognitive decline. The p38 MAPK pathway plays a crucial role in tau protein phosphorylation and inflammation in AD. A phenyl sulfonamide derivative Sulfo (I) shows better binding affinity and stability, suggesting its potential as a therapeutic target for combating AD.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Sung Min Cho, Yonghyo Kim, Yooju Jung, Minjeong Ko, Gyorgy Marko-Varga, Ho Jeong Kwon
Summary: A novel natural small molecule, voacangine (Voa), has been discovered as a potent antiangiogenic compound that directly binds to and inhibits the kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2). Synthetic molecules based on Voa's chemical structure, such as Voa analogue 19 (V19), show increased antiangiogenic potency without cytotoxic effects and induce significant tumor cell death in a mouse xenograft model. This VEGFR2 modulator, inspired by the natural compound Voa's rigid scaffold, presents a promising candidate for development of new antiangiogenic agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shanelle Shillingford, Lei Zhang, Yulia Surovtseva, Sam Dorry, Elias Lolis, Anton M. Bennett
Summary: This study demonstrates the importance of a specific site (Y271) in the phosphatase domain of MKP7 for its catalytic activity and binding to p38 MAPK and JNK. Mutations in this site inhibited MKP7 function, leading to increased nuclear accumulation of p38 MAPK and JNK. These findings contribute to our understanding of the regulatory mechanisms of MKP7 and provide insights for potential therapeutic targeting of MKP7.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Chenchen Bian, Xiangtong Yuan, Caihong Zeng, Jian Sun, Gen Kaneko, Hong Ji
Summary: This study investigated the mechanism of docosahexaenoic acid (DHA)-induced apoptosis mediated by mitophagy, using grass carp as an animal model. The results showed that inhibition of mitophagy alleviated apoptosis and eliminated the inhibition of lipid accumulation induced by DHA. Mechanistically, DHA induced mitophagy by activating the PPAR gamma-LC3-BNIP3 pathway. Inhibition of PPAR gamma decreased autophagy-related gene expression and prevented BNIP3/NIX-mediated mitophagy-induced apoptosis, thereby alleviating the inhibition of lipid accumulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Venkatesan Ramya, Karuppiah Prakash Shyam, Arulanandu Angelmary, Balamuthu Kadalmani
Summary: This study reveals that Lauric acid (LA) exerts an epigenetic regulation and metabolic reprogramming on SH-SY5Y neuroblastoma cells through modulation of lncRNA HOTAIR, remodeling of chromatin H3K4 tri-methylation and regulation of glucose uptake by controlling NF-kappa B activation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Sreelekshmi Sreekumar, Karyath Palliyath Gangaraj, Manikantan Syamala Kiran
Summary: This study investigates the intricate interplay between angiogenic regulation and the browning of white adipocytes. The findings reveal that concurrent activation of angiogenesis is necessary for inducing browning of white adipocytes. The study also highlights the role of Vascular endothelial growth factor (VEGF) in promoting angiogenesis and triggering the browning process through the activation of Estrogen receptor alpha (ER alpha) signaling pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Zanxia Cao, Liling Zhao, Mingcui Chen, Zhihong Shi, Lei Liu
Summary: This study investigated the translocation process of cholesterol/calcitriol in bacterial membranes and their effects on membrane structure. Calcitriol facilitated water transport across the membrane, while cholesterol had the opposite effect. These findings contribute to a better understanding of the relationship between cholesterol/calcitriol concentrations, lipid bilayer structure, and water permeation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Xiaozhen Guo, Jiawen Wang, Hualing Xu, Yangyang Wang, Yutang Cao, Yingquan Wen, Jiaqi Li, Yameng Liu, Kanglong Wang, Jue Wang, Xianchun Zhong, Chuying Sun, Yongxin Zhang, Jingyi Xu, Cuina Li, Pengxiang Mu, Lingyan Xu, Cen Xie
Summary: This study aims to investigate the role of the gut microbiota-bile acid axis in regulating the diurnal rhythms of metabolic homeostasis and assess the impact of obesity on them. The results show that high fat diet feeding and Leptin gene deficiency disrupt the rhythmic patterns of insulin sensitivity and serum total cholesterol levels. The study provides compelling evidence for the association between diurnal rhythm of insulin sensitivity and gut microbiota-bile acid axis, and elucidates the deleterious effects of obesity on gut microbiome-bile acid metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Giuseppe Pepe, Maria Cotugno, Federico Marracino, Luca Capocci, Ludovica Pizzati, Maurizio Forte, Rosita Stanzione, Pamela Scarselli, Alba Di Pardo, Sebastiano Sciarretta, Massimo Volpe, Speranza Rubattu, Vittorio Maglione
Summary: The study found that enzymes involved in sphingolipid metabolism show abnormal expression in the cardiac tissue of hypertensive rat models, which may be related to the susceptibility to cardiac damage.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)