Article
Chemistry, Multidisciplinary
Zi-hua Song, Xiang-Jie Song, Chen-ling Yang, Peng Cao, Yu Mao, Yan Jin, Meng-yun Xu, Hai-tao Wang, Xia Zhu, Wei Wang, Zhi Zhang, Wen-juan Tao
Summary: Diabetic patients often suffer from neuropathic pain, for which effective treatments are currently lacking. This study reveals that dysfunction of microglia, a type of cell in the central nervous system, contributes to the development of diabetic pain. Specifically, the activation of microglia and the upregulation of the chemokine CXCL12 and its receptor CXCR4 in the anterior cingulate cortex lead to hyperactivity of glutamatergic neurons and pain sensitization in diabetic mice.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Neurosciences
Mikako Hirose, Mito Asano, Saori Watanabe-Matsumoto, Koji Yamanaka, Yoichiro Abe, Masato Yasui, Eiichi Tokuda, Yoshiaki Furukawa, Hidemi Misawa
Summary: The study indicates that abnormal expression and mislocalization of AQP4 in SOD1(G93A) mice result in dysfunction of the glymphatic system, leading to delayed waste clearance and exacerbation of ALS disease progression.
NEUROSCIENCE RESEARCH
(2021)
Article
Fisheries
Along Gao, Lan Li, Fangfang Yan, Yang Lei, Jianlin Chen, Liting Wu, Jianmin Ye
Summary: The study identified and characterized a homolog of CXCR4 in Nile tilapia, which plays crucial roles in host defense against bacterial infection and inflammation by responding to CXCL12.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Natalia Nowicka, Kamila Szymanska, Judyta Juranek, Kamila Zglejc-Waszak, Agnieszka Korytko, Michal Zalecki, Malgorzata Chmielewska-Krzesinska, Krzysztof Wasowicz, Joanna Wojtkiewicz
Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unclear pathogenesis. RAGE and its ligands have been found to play an important role in the pathogenesis of ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Veronica Granatiero, Nicole M. Sayles, Angela M. Savino, Csaba Konrad, Michael G. Kharas, Hibiki Kawamata, Giovanni Manfredi
Summary: ALS is a complex disease involving motor neuron degeneration, with emerging evidence suggesting the importance of astrocytes and the MTOR pathway in disease pathogenesis. Modulation of the astrocytic IGF1R-MTOR pathway may present a potential therapeutic strategy for SOD1 ALS and other neurological disorders.
Article
Pharmacology & Pharmacy
Nuria Gaja-Capdevila, Neus Hernandez, Xavier Navarro, Mireia Herrando-Grabulosa
Summary: The study demonstrated that Sig-1R ligands, including three different drugs, can partially alleviate muscle function impairment in ALS patients and increase the number of surviving motor neurons. Furthermore, these drugs showed varying effects in improving muscle function and protecting neuromuscular junctions. Although more research is needed to determine their exact mechanisms of action, Sig-1R ligands have the potential to be promising tools for ALS treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Meng Zhang, Yi Liu, Jing Chen, Lei Chen, Li Zhang, Xianguo Chen, Zongyao Hao, Chaozhao Liang
Summary: This study identified highly expressed factors in the prostate tissues of CNP mice and found that targeting the CXCL12/CXCR4 axis could alleviate inflammation. The study also explored the influence of this axis on downstream signaling pathways.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Li Xing, Hai-Tao Lv, San-Guang Liu, Wen-Bin Wang, Teng-Fei Zhang, Jian-Hua Liu, Wei Bian
Summary: The study confirmed the inhibitory effect of gemcitabine on the growth of cholangiocarcinoma RBE cells and demonstrated its impact on the expression levels of cell-related proteins and mRNA. Combination of AMD3100 with gemcitabine reduced cell invasion and metastasis-related factors.
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Biochemical Research Methods
Lin Chen, Ningyuan Wang, Yingzhen Zhang, Dongxiao Li, Caili He, Zhongzhong Li, Jian Zhang, Yansu Guo
Summary: This study analyzed the differentially expressed proteins (DEPs) in the spinal cord of ALS mice at the onset stage. The findings suggest that immunity and inflammation play a crucial role in the early development of ALS. Additionally, potential biomarkers were identified, providing new insights into the pathological mechanisms of ALS.
JOURNAL OF PROTEOMICS
(2023)
Article
Pharmacology & Pharmacy
Guowen Lu, Yier Qiu, Xiaobao Su
Summary: Insufficient T cell infiltration in triple-negative breast cancer (TNBC) has led to limited responses to immune checkpoint blockade (ICB) therapies, prompting the development of immunostimulatory approaches. A novel CXCR4-targeted liposomal formulation was developed to enhance the therapeutic efficacy of AMD3100, a CXCR4 antagonist, leading to improved immune activation and antitumor effects in a murine TNBC model when combined with anti-PD-L1 therapy.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Eleonore Bertin, Audrey Martinez, Anne Fayoux, Kevin Carvalho, Sara Carracedo, Pierre-Olivier Fernagut, Friedrich Koch-Nolte, David Blum, Sandrine S. Bertrand, Eric Boue-Grabot
Summary: This study reveals the abnormal expression of P2X4 receptor in patients with amyotrophic lateral sclerosis (ALS), suggesting its potential as a candidate early biomarker for ALS. The study also uncovers how misfolded proteins related to ALS impact the trafficking of P2X4, providing important clues for a better understanding of the pathological mechanism of ALS.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Morgan M. Highlander, Sherif M. Elbasiouny
Summary: Spinal direct current stimulation can modulate motoneuron excitability and potentially serve as a neurorehabilitation therapy for ALS. A pilot study on mice found that transcutaneous direct current stimulation had limited primary effects due to the need to avoid skin damage. However, analysis showed a potential harmful effect of anodal stimulation at symptom onset, suggesting cathodal stimulation may be beneficial if higher stimulation intensity can be achieved safely.
BIOENGINEERING-BASEL
(2022)
Article
Cell & Tissue Engineering
Ying-Ying Chen, Yu-Feng Liu, Yong-Dong Liu, Xiao-Hui Deng, Jie Zhou
Summary: IRF7 is an important regulator of stress hematopoiesis, as its deficiency enhances stem cell regeneration and long-term repopulation under stress conditions. Mechanistic studies reveal CXCR4 as a downstream target of IRF7, with overexpression of CXCR4 abolishing the enhanced proliferation and regeneration observed in IRF7-deficient HSPCs.
Article
Neurosciences
Svitlana Garbuzova-Davis, Kayla J. Boccio, Alexander Llauget, Robert Shell, Surafuale Hailu, Hilmi Mustafa, Jared Ehrhart, Paul R. Sanberg, Stanley H. Appel, Cesario V. Borlongan
Summary: In ALS research, treatment with human bone marrow-derived stem cells in mutant mice significantly increased levels of tight junction proteins, capillary pericyte coverage, and endothelial cytoskeletal F-actin expressions, helping to repair the barrier and prolong motor neuron survival.
Article
Cell Biology
Gaetano D'Amato, Ragini Phansalkar, Jeffrey A. Naftaly, Xiaochen Fan, Zhainib A. Amir, Pamela E. Rios Coronado, Dale O. Cowley, Kelsey E. Quinn, Bikram Sharma, Kathleen M. Caron, Alessandra Vigilante, Kristy Red-Horse
Summary: Endocardial cells have the potential to differentiate into coronary endothelial cells and regenerate blood vessels lost during cardiac injury. This study used mouse genetics and scRNA-seq to identify the molecular mechanisms involved in endocardial angiogenesis. It was found that CXCL12/CXCR4 signaling is specifically required for artery morphogenesis, and a transitioning population expressing Bmp2 was identified as important during mid-gestation.
DEVELOPMENTAL CELL
(2022)
Article
Cardiac & Cardiovascular Systems
Rimpy Dhingra, Matthew Guberman, Inna Rabinovich-Nikitin, Jonathon Gerstein, Victoria Margulets, Hongying Gang, Nicholas Madden, James Thliveris, Lorrie A. Kirshenbaum
CARDIOVASCULAR RESEARCH
(2020)
Editorial Material
Cardiac & Cardiovascular Systems
Inna Rabinovich-Nikitin, Matthew Love, Lorrie A. Kirshenbaum
CARDIOVASCULAR RESEARCH
(2021)
Article
Neurosciences
Yuval Gavriel, Inna Rabinovich-Nikitin, Assaf Ezra, Becki Barbiro, Beka Solomon
JOURNAL OF ALZHEIMERS DISEASE
(2020)
Editorial Material
Medicine, Research & Experimental
Inna Rabinovich-Nikitin, Lorrie A. Kirshenbaum
Summary: Lysosomal storage disorders (LSD) are inherited metabolic diseases affecting the heart. Modulation of TFEB alone is not enough to rescue the underlying clearance defect in LSD, with the YAP/TFEB signaling pathway identified as a key regulator of autophagosomes. Accumulation of undigested autophagosomes leads to cell death and cardiac dysfunction in LSD.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Pharmacology & Pharmacy
Iman S. Aziz, Adam M. McMahon, David Friedman, Inna Rabinovich-Nikitin, Lorrie A. Kirshenbaum, Tami A. Martino
Summary: This article discusses the importance of circadian rhythms for cardiovascular health and disease, as well as the circadian influence on inflammatory responses in heart disease. The focus is on elucidating the role and regulatory mechanisms of the circadian system in influencing inflammation in heart disease.
CURRENT OPINION IN PHARMACOLOGY
(2021)
Article
Cell Biology
Inna Rabinovich-Nikitin, Mina Rasouli, Cristine J. Reitz, Illana Posen, Victoria Margulets, Rimpy Dhingra, Tarak N. Khatua, James A. Thliveris, Tami A. Martino, Lorrie A. Kirshenbaum
Summary: This study reveals that the CLOCK gene transcriptionally coordinates mitochondrial quality control mechanisms in cardiac myocytes, regulating an adaptive stress response crucial for cell survival. Restoring CLOCK activity may be beneficial in reducing cardiac injury in individuals with disrupted circadian rhythms.
Editorial Material
Cardiac & Cardiovascular Systems
Inna Rabinovich-Nikitin, Lorrie A. Kirshenbaum
Editorial Material
Cardiac & Cardiovascular Systems
Inna Rabinovich-Nikitin, Rachel C. Cogan, Lorrie A. Kirshenbaum
CIRCULATION RESEARCH
(2021)
Editorial Material
Cell Biology
Yuval Gavriel, Inna Rabinovich-Nikitin, Beka Solomon
NEURAL REGENERATION RESEARCH
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Inna Rabinovich-Nikitin, Lorrie A. Kirshenbaum
TRENDS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Inna Rabinovich-Nikitin, Matthew Love, Lorrie A. Kirshenbaum
Summary: Autophagy is an important cellular mechanism for removing damaged or dysfunctional cellular components. It plays a crucial role in the cardiovascular system and contributes to normal cardiac function. The activation of autophagy during cardiac stress can be adaptive or maladaptive. This review highlights the molecular mechanisms and signaling pathways underlying autophagy in response to cardiac stress, as well as therapeutic approaches to modulate autophagy. The intersection between autophagy and circadian regulation in the heart is also discussed.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Emmanouil Zacharioudakis, Bogos Agianian, Vasantha Kumar Mv, Nikolaos Biris, Thomas P. Garner, Inna Rabinovich-Nikitin, Amanda T. Ouchida, Victoria Margulets, Lars Ulrik Nordstrom, Joel S. Riley, Igor Dolgalev, Yun Chen, Andre J. H. Wittig, Ryan Pekson, Chris Mathew, Peter Wei, Aristotelis Tsirigos, Stephen W. G. Tait, Lorrie A. Kirshenbaum, Richard N. Kitsis, Evripidis Gavathiotis
Summary: Mitofusins are proteins that regulate mitochondrial fusion, a process with significant impact on cellular processes. This study identifies small molecules that can activate or inhibit Mitofusins' activity, thereby modulating mitochondrial fusion and functionality. Inhibition of mitochondrial fusion leads to certain physiological changes such as caspase-3/7 activation and DNA damage. The findings highlight the importance of Mitofusins' conformational changes and oligomerization in enabling mitochondrial fusion. The study provides insights into the function and regulation of Mitofusins and offers potential small molecules for pharmacological targeting.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Inna Rabinovich-Nikitin, Alexandra Blant, Rimpy Dhingra, Lorrie A. Kirshenbaum, Michael P. Czubryt
Summary: Hypoxia has broad effects on cardiomyocyte function and viability, and this study reveals that the transcriptional coactivator PGC-1 alpha is down-regulated in hypoxia through the nuclear localization of NF-kappa B p65 subunit and its association with the PGC-1 alpha promoter.
Review
Pharmacology & Pharmacy
Inna Rabinovich-Nikitin, Molly Crandall, Lorrie A. Kirshenbaum
Summary: Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Differences in sex can impact the etiology and outcome of cardiovascular disease differently in men and women. Women have unique genetic and hormonal risk factors associated with the development of cardiovascular diseases. Certain phenotypes of cardiovascular diseases are also more prevalent in women.
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Rimpy Dhingra, Inna Rabinovich-Nikitin, Sonny Rothman, Matthew Guberman, Hongying Gang, Victoria Margulets, Davinder S. Jassal, Keshav N. Alagarsamy, Sanjiv Dhingra, Carla Valenzuela Ripoll, Filio Billia, Abhinav Diwan, Ali Javaheri, Lorrie A. Kirshenbaum
Summary: The study reveals that doxorubicin (DOX) interferes with NF-κB activation by TNFα in cardiac myocytes, possibly due to proteasomal degradation of TRAF2. The degradation of TRAF2 is regulated by cellular inhibitors of apoptosis 1 and USP19. Loss of TRAF2 leads to increased sensitivity of cardiac myocytes to TNFα-mediated necrotic cell death and DOX cardiotoxicity.