Frederik Denorme, Bhanu Kanth Manne, Irina Portier, Aaron C Petrey, Elizabeth Middleton, Benjamin T Kile, Matthew T Rondina, Robert A Campbell
BACKGROUND: Emerging evidence implicates dysfunctional platelet responses in thrombotic complications in COVID-19 patients. Platelets are important players in inflammation-induced thrombosis. In particular, procoagulant platelets support thrombin generation and mediate thromboinflammation. OBJECTIVES: To examine if procoagulant platelets formation is altered in COVID-19 patients and if procoagulant platelets contribute to pulmonary thrombosis. PATIENTS/METHODS: Healthy donors and COVID-19 patients were recruited from the University of Utah Hospital System...
September 18, 2020: Journal of Thrombosis and Haemostasis: JTH
Yuehuan Zheng, Zhe Chen, Chang She, Yazhou Lin, Yuan Hong, Liqiang Shi, Yingzi Zhang, Peng Cao, Xiangyang Xu
Four-octyl itaconate (4-OI) is the cell-permeable derivative of itaconate that can activate Nrf2 signaling by alkylating Keap1's cysteine residues. Here, we tested the potential effect of 4-OI on hydrogen peroxide (H2 O2 )-induced oxidative injury in osteoblasts. In OB-6 cells and primary murine osteoblasts, 4-OI was able to activate Nrf2 signaling cascade and cause Keap1-Nrf2 disassociation, Nrf2 protein stabilization, cytosol accumulation, and nuclear translocation. 4-OI also augmented antioxidant-response element reporter activity and promoted expression of Nrf2-dependent genes (HO1, NQO1, and GCLC)...
September 17, 2020: Cell Death & Disease
Ziv Spiegelman, Or Broshi, Amit Shahar, Sumita Omer, Hagit Hak, Shmuel Wolf
The phloem-mobile protein SlCyp1 traffics to distant parts of the shoot to regulate its gravitropic response. In addition, SlCyp1 targets specific cells in the root to promote lateral root development. The tomato (Solanum lycopersicum) Cyclophilin 1 (SlCyp1) gene encodes a peptidyl-prolyl isomerase required for auxin response, lateral root development and gravitropic growth. The SlCyp1 protein is a phloem-mobile signal that moves from shoot to root to regulate lateral root development (Spiegelman et al., Plant J 83:853-863, 2015; J Exp Bot 68:953-964, 2017a)...
September 16, 2020: Planta
James H Morrison, Caitlin Miller, Laura Bankers, Gary Crameri, Lin-Fa Wang, Eric M Poeschla
Bats are primary reservoirs for multiple lethal human viruses, such as Ebola, Nipah, Hendra, rabies, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and, most recently, SARS-CoV-2. The innate immune systems of these immensely abundant, anciently diverged mammals remain insufficiently characterized. While bat genomes contain many endogenous retroviral elements indicative of past exogenous infections, little is known about restrictions to extant retroviruses...
September 15, 2020: MBio
Xiaobo Zhang, Ying Zhu, Ying Zhou, Bingru Fei
BACKGROUND Diabetic nephropathy (DN), the formation of albuminuria, is one of the most important complications seen in diabetic patients. IL-37, an inhibitor of congenital inflammation and immune response, plays an important role in the occurrence and development of diabetes, but its study in DN has not been previously reported. MATERIAL AND METHODS Podocyte transfection techniques were used to overexpress STAT3 and cyclophilin A (CypA). The expression of IL-37, STAT3, and CypA was detected by RT-qPCR and western blot...
September 15, 2020: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Zoya Niatsetskaya, Sergey Sosunov, Anna Stepanova, James Goldman, Alexander Galkin, Maria Neginskaya, Evgeny Pavlov, Vadim Ten
Postnatal failure of oligodendrocyte maturation has been proposed as a cellular mechanism of diffuse white matter injury (WMI) in premature infants. However, the molecular mechanisms for oligodendrocyte maturational failure remain unclear. In neonatal mice and cultured differentiating oligodendrocytes, sublethal intermittent hypoxic (IH) stress activated cyclophilin D-dependent mitochondrial proton leak and uncoupled mitochondrial respiration, leading to transient bioenergetic stress. This was associated with development of diffuse WMI: poor oligodendrocyte maturation, diffuse axonal hypomyelination, and permanent sensorimotor deficit...
September 14, 2020: Journal of Clinical Investigation
Hon-Kan Yip, Pei-Lin Shao, Christopher Glenn Wallace, Jiunn-Jye Sheu, Pei-Hsun Sung, Mel S Lee
This study tested the hypothesis that early implantation of mitochondria (Mito) into left myocardium could effectively protect heart against doxorubicin/12 mg/kg-induced dilated cardiomyopathy (DCM) in rat. Adult-male SD rats (n = 18) were equally categorized into group 1 (sham control), group 2 (DCM) and group 3 [DCM + Mito (500 μg/rat intramyocardial injection by day-21 after DCM induction)] and euthanized by day 60. In vitro studies showed that exogenously-transferred Mito was abundantly identified in H9C2 cells...
2020: American Journal of Translational Research
Xiaoli Li, Jinhe Han, Hye Won Lee, Yi-Seul Yoon, Yifeng Jin, Daulat B Khadka, Suhui Yang, Meehyein Kim, Won-Jea Cho
The therapy of chronic hepatitis C virus infections has significantly improved with the development of direct-acting antivirals (DAAs), which contain NS3/4A protease, NS5A, and NS5B polymerase inhibitors. However, mutations in specific residues in these viral target genes are associated with resistance to the DAAs. Especially inhibitors of NS3/4A protease and NS5A, such as grazoprevir and velpatasvir, have a low barrier to resistant mutations. As a result, the mutations influence the virological outcomes after DAA treatment...
October 1, 2020: Bioorganic & Medicinal Chemistry
Qiang Ge, Yongyan Tang, Wei Luo, Jingyu Zhang, Kang Chong, Yunyuan Xu
BACKGROUND: Grain size is one of the key agronomic traits that impact grain yield. Several regulatory pathways had been reported to participate in grain size determination via cell expansion or proliferation in rice. However, little is known about cyclophilin and spliceosome participation in grain shape regulation. RESULTS: Here, we identified OsCYP20-2, a cyclophilin that influences spliceosome assembly to determine grain length. oscyp20-2 t1, a knock out mutant of OsCYP20-2 caused by T-DNA insertion, produced shorter grains with deficient cell elongation...
September 10, 2020: Rice
Qishan Wang, Bingxin Xu, Kaijian Fan, Jing Wu, Tingyu Wang
To investigate the crosstalk between cartilage and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), we adopted an in vitro coculture system model of collagen-induced arthritis (CIA) cartilage and CIA FLS monolayer. CIA rat samples of the synovium and femur head were collected for isolation of FLS and coculture system. Cartilages were treated with vehicle (Ctrl group), 10 ng/mL interleukin- (IL-) 1 α (IL-1 α group), and 10 ng/mL IL-1 α plus 10  μ M dexamethasone (Dex group) for 3 days before coculture with FLS for further 2 days...
2020: Mediators of Inflammation
Augustin Penda Twizerimana, Rachel Scheck, Daniel Becker, Zeli Zhang, Marianne Wammers, Leandro Avelar, Marc Pflieger, Dieter Häussinger, Thomas Kurz, Holger Gohlke, Carsten Münk
Pandemic HIV-1 is the result of zoonotic transmission of Simian immunodeficiency virus (SIV) from chimpanzee species Pan troglodytes troglodytes (SIVcpzPtt). The related Pan troglodytes schweinfurthii is the host of a similar virus, SIVcpzPts, which did not spread to humans.We tested these viruses with small-molecule capsid inhibitors (PF57, PF74, and GS-CA1) that interact with a binding groove in the capsid that is also used by CPSF6. While HIV-1 was sensitive to capsid inhibitors in cell lines, human macrophages and PBMCs, SIVcpzPtt was resistant in rhesus FRhL-2 cells and human PBMCs but was sensitive to PF74 in human HOS and HeLa cells...
September 9, 2020: Journal of Virology
Manman Lu, Ryan W Russell, Alexander J Bryer, Caitlin M Quinn, Guangjin Hou, Huilan Zhang, Charles D Schwieters, Juan R Perilla, Angela M Gronenborn, Tatyana Polenova
HIV-1 capsid plays multiple key roles in viral replication, and inhibition of capsid assembly is an attractive target for therapeutic intervention. Here, we report the atomic-resolution structure of capsid protein (CA) tubes, determined by magic-angle spinning NMR and data-guided molecular dynamics simulations. Functionally important regions, including the NTD β-hairpin, the cyclophilin A-binding loop, residues in the hexamer central pore, and the NTD-CTD linker region, are well defined. The structure of individual CA chains, their arrangement in the pseudo-hexameric units of the tube and the inter-hexamer interfaces are consistent with those in intact capsids and substantially different from the organization in crystal structures, which feature flat hexamers...
September 2020: Nature Structural & Molecular Biology
Xuejiao Zhu, Libin Wen, Wei Wang, Qi Xiao, Kongwang He
Porcine circovirus type2 (PCV2) is a member of the circoviridae family. PCV2 was identified as the main pathogen of postweaning multisystemic wasting syndrome (PMWS) in weaned piglets and causes massive economic loss. Basigin, is a transmembrane glycoprotein belonging to the immunoglobulin superfamily; which is also a receptor for cyclophilins. CyP belongs to the immunophilin family that has peptidyl-prolyl cis-trans isomerase activity. Basigin-CyP interaction affects the replication stages of several viruses...
September 4, 2020: Virus Research
Arihide Okahara, Jun-Ichiro Koga, Tetsuya Matoba, Masaki Fujiwara, Masaki Tokutome, Gentaro Ikeda, Kaku Nakano, Masaki Tachibana, Tetsuro Ago, Takanari Kitazono, Hiroyuki Tsutsui, Kensuke Egashira
Ischemia-reperfusion injury impairs the efficacy of reperfusion therapy after ischemic stroke. Cyclophilin D (CypD)-mediated openings of mitochondrial permeability transition pore (mPTP) and subsequent monocyte-mediated inflammation are considered as major mechanisms of reperfusion injury. However, no medical therapies are currently available. Therefore, we have tested a hypothesis that simultaneous targeting of mPTP and inflammation confers substantial neuroprotection after cerebral ischemia-reperfusion. To address this point, we prepared CypD knockout mice, C-C chemokine receptor 2 (CCR2) knockout mice and CypD/CCR2 double knockout mice...
September 2, 2020: Scientific Reports
Michela Carraro, Kristen Jones, Geppo Sartori, Marco Schiavone, Salvatore Antonucci, Roza Kucharczyk, Jean-Paul di Rago, Cinzia Franchin, Giorgio Arrigoni, Michael Forte, Paolo Bernardi
The mitochondrial permeability transition pore (PTP) is a Ca2+ -activated channel that plays a key role in cell death. Thiol oxidation facilitates PTP opening, yet the targets and molecular mechanisms still await a definition. Here, we investigate the role of C141 of F-ATP synthase oligomycin sensitivity conferral protein (OSCP) subunit in PTP modulation by oxidation. We find that the OSCP C141S mutation confers resistance to PTP opening and cell death by diamide and MitoParaquat only when cyclophilin D (CyPD) has been ablated, a protective role that can be explained by CyPD shielding C141 from oxidants...
September 1, 2020: Cell Reports
Tao Jiang, Shiyun Dai, Yiwen Yi, Yi Liu, Shuai Zhang, Mingcui Luo, Hui Wang, Dan Xu
Hippocampus, as an important organ of central memory storage and spatial orientation, has been studied increasingly in recent years. The expression of reference genes in the hippocampus of adult rats, which are commonly used in the quantitative real-time polymerase chain reaction (qRT-PCR), is unstable in the fetal hippocampus and may not be suitable for the fetal period. Therefore, this study intends to screen and determine the optimal compound reference genes in the fetal rat hippocampus. Based on the literature, we selected five house-keeping genes (HKGs), including glyceraldehyde 3-phosphate dehydrogenase (gapdh), actin beta (β-actin), hypoxanthine phosphoribosyltransferase (hprt), 18s ribosomal RNA (18s rRNA), and cyclophilin B (cypB)...
September 2, 2020: Developmental Neurobiology
Alessandra Monti, Mattia Sturlese, Andrea Caporale, Jessica De Almeida Roger, Fabiola Mascanzoni, Menotti Ruvo, Nunzianna Doti
BACKGROUND: The neuronal apoptotic process requires the nuclear translocation of Apoptosis Inducing Factor (AIF) in complex with Cyclophilin A (CypA) with consequent chromatin condensation and DNA degradation events. Targeting CypA by delivering an AIF-blocking peptide (AIF(370-394)) provides a significant neuroprotection, demonstrating the biological relevance of the AIF/CypA complex. To date pharmaceutical compounds targeting this complex are missing. METHODS: We designed and synthesized a set of mono and bicyclic AIF(370-394) analogs containing both disulfide and 1,2,3-triazole bridges, in the attempt to both stabilize the peptide conformation and improve its binding affinity to CypA...
August 27, 2020: Biochimica et Biophysica Acta. General Subjects
Sarita Aryal, Hong-Ming Hsu, Yuan-Chao Lou, Chien-Hsin Chu, Jung-Hsiang Tai, Chun-Hua Hsu, Chinpan Chen
In Trichomonas vaginalis ( T. vaginalis ), cyclophilins play a vital role in dislodging Myb proteins from the membrane compartment and leading them to nuclear translocation. We previously reported that Tv CyP1 cyclophilin from T. vaginalis forms a dimer and plays an essential role in moving the Myb1 transcription factor toward the nucleus. In comparison, Tv CyP2 containing an extended segment at the N-terminus (N-terminal segment) formed a monomer and showed a different role in regulating protein trafficking...
August 26, 2020: Biomolecules
Haoyue Hu, Jiayi Jiang, Qian Chen, Songren Wei, Mian Liu, Xia Chen, Cuixia Fan, Jing Ma, Wenqian Chen, Xuefei Wang, Mei Zhong
AIMS: Numerous studies suggest that excessive maternal inflammation and defective extravillous trophoblast (EVT) invasion could contribute to the development of preeclampsia (PE), but the underlying mechanism remains unclear. Some evidence suggests that CyPA is elevated in PE. This research aims to investigate the effect of recombinant human CyPA on trophoblast migration and invasion both in vitro and in vivo. MATERIALS AND METHODS: We detected the expression and localization of CyPA in human placenta and explored the effects of CyPA on cell migration and invasion on HTR8/SVneo cell...
August 25, 2020: Life Sciences
Jeremias Bayon, Amparo Alfonso, Sandra Gegunde, Eva Alonso, Rebeca Alvarino, Melisa Santas-Alvarez, Ana Testa-Fernandez, Ramon Rios-Vazquez, Luis Botana, Carlos Gonzalez-Juanatey
Background: Cyclophilins (Cyps) are a family of peptidyl-prolyl cis/trans isomerases consistently involved in cardiovascular diseases through the inflammation pathway. This study aims to investigate the serum levels of Cyps (CypA, CypB, CypC and CypD) in patients with coronary artery disease (CAD) and the correlation with clinical characteristics and inflammation parameters. Methods: We developed an observational prospective study with a total of 125 subjects: 40 patients with acute CAD, 40 patients with chronic CAD and 45 control volunteers, in whom serum levels of Cyps (CypA, CypB, CypC and CypD), interleukins and metalloproteinases were measured...
October 2020: Cardiology Research
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