Article
Cardiac & Cardiovascular Systems
Di Ren, Julia Fedorova, Kayla Davitt, Tran Ngoc Van Le, John H. Griffin, Patricia Chia-Ying Liaw, Charles Esmon, Alireza R. Rezaie, Ji Li
Summary: This study investigates the role of the APC-EPCR axis in ischemic insults in aging. The results show that APC activity is reduced during cardiac ischemia and reperfusion, and this reduction is more pronounced in aged hearts. Administration of APC prevents the shedding of EPCR induced by I/R and improves cardiac dysfunction in both young and aged mice. However, these cardioprotective effects of APC are diminished in EPCRR84A/R84A mice. AMPK mediates acute adaptive response while AKT is involved in chronic metabolic programming in APC-treated hearts.
CIRCULATION RESEARCH
(2022)
Review
Neurosciences
Linda Ines Zoungrana, Steven Didik, Hao Wang, Lily Slotabec, Ji Li
Summary: Epilepsy is a common neurologic disorder characterized by recurrent seizures. The mechanism of development is not fully understood, but activated protein C (APC) has potential neuroprotective effects through its anti-inflammatory, anti-apoptotic, and neurogenic actions.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Gabriella D'Orazi, Marco Cordani, Mara Cirone
Summary: Inflammation and cancerogenesis are closely linked, driven by pathways such as NF-kB, STAT3, mTOR and MAPKs that regulate the release of pro-inflammatory cytokines, impacting immune response and tumor suppressor p53 stability.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Giulia Di Rocco, Antonio Ranieri, Marco Borsari, Marco Sola, Carlo Augusto Bortolotti, Gianantonio Battistuzzi
Summary: The Met80Ala variant of yeast cytochrome c shows promising biocatalytic and biosensing properties due to its stable electrocatalytic properties in mixed solvents. Organic solvents have minimal effects on the redox and structural properties of the variant.
Article
Food Science & Technology
Barbara G. de Freitas, Natalia G. Hoesch, Leandro M. Pereira, Tereza C. Barbosa, Gisele Picolo, Yara Cury, Vanessa O. Zambelli
Summary: Crotalphine, a peptide from the venom of South American rattlesnake, induces potent and long-lasting antinociceptive effect through the activation of peripheral opioid receptors. This effect is dependent on the PKC zeta-ERK signaling pathway, inhibition of which blocks the analgesic effect of Crotalphine. These findings suggest the PKC zeta-MAPK axis as a potential target for pain control.
Article
Pharmacology & Pharmacy
Jacklyn Nguyen, Brittnie S. Armstrong, Sophie Cowman, Yaniv Tomer, Shivakumar R. Veerabhadraiah, Michael F. Beers, Alessandro Venosa
Summary: This study investigates the role of eosinophils in inflammatory exacerbations and their potential as therapeutic targets. The deletion of eosinophils improves lung histology and reduces inflammation, suggesting their detrimental role in lung fibrosis. Additionally, corticosteroid treatment shows efficacy in reducing eosinophil counts and alleviating structural damage.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Hematology
Xian Li, Xiaohong Song, Dlovan F. D. Mahmood, Martha M. S. Sim, Sara J. Bidarian, Jeremy P. Wood
Summary: TFPIα and APC exhibit stronger anticoagulant activity when combined with PS, while antibodies against TFPI and APC have an additive procoagulant effect. In purified protein systems, TFPIα dose-dependently inhibits thrombin activation by prothrombinase only in the presence of APC, and this activity is enhanced by PS. Platelets protect prothrombinase from inhibition, maintaining a procoagulant environment within the clot.
THROMBOSIS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Dahlia Palevski, Gil Ben-David, Yehonatan Weinberger, Rabeei Haj Daood, Jose A. Fernandez, Ivan Budnik, Sarina Levy-Mendelovich, Gili Kenet, Yael Nisgav, Dov Weinberger, John H. Griffin, Tami Livnat
Summary: 3K3A-APC has been shown to have anti-inflammatory properties and may be a novel treatment for retinal diseases associated with inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Xiaofeng Cai, Sumith R. Panicker, Indranil Biswas, Hemant Giri, Alireza R. Rezaie
Summary: The study demonstrates that APC and a signaling-selective mutant of APC effectively inhibit the proinflammatory signaling effects of poly(I:C) in both cellular and animal models. The integrin Mac-1 is involved in the APC inhibition of macrophage ET formation, suggesting a key role for APC signaling in inhibiting proinflammatory responses induced by viral mimetics.
THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Cell Biology
Wen-Yi Lin, Liang Tang, Xuan Lu, Yu Hu
Summary: The APC K150del mutant displays concentration-dependent effects on anti-inflammatory and anti-apoptotic activities, with higher concentrations restoring these effects while lower concentrations decrease them. Furthermore, the mutant enhances the expression of virus defense-related genes in mouse lung tissues.
Article
Multidisciplinary Sciences
Maya Spichal, Bree Heestand, Katherine Kretovich Billmyre, Stephen Frenk, Craig C. Mello, Shawn Ahmed
Summary: The sterility of the C. elegans Piwi prg-1 mutant is not associated with transposon-induced DNA damage, but is instead associated with and phenocopied by dysfunction of germ granules.
NATURE COMMUNICATIONS
(2021)
Review
Endocrinology & Metabolism
Balamurugan Dhayalan, Deepak Chatterjee, Yen-Shan Chen, Michael A. Weiss
Summary: Analysis of diabetes-associated mutations in the human insulin gene has provided insights into the folding mechanisms of proinsulin, revealing the impact of mutations on pancreatic beta-cell dysfunction and insulin secretion. Studies suggest that conserved residues play a crucial role in folding efficiency and the susceptibility of proinsulin to impaired foldability can contribute to the development of diseases. This highlights the molecular links between biophysical principles and the impact on diseases such as diabetes and obesity.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Hematology
Josepha C. Sedzro, Frederic Adam, Claire Auditeau, Elsa Bianchini, Allan De Carvalho, Ivan Peyron, Sadyo Darame, Sophie Gandrille, Stella Thomassen, Tilman M. Hackeng, Olivier D. Christophe, Peter J. Lenting, Cecile Denis, Delphine Borgel, Francois Saller
Summary: The research team generated a PS-specific sdAb (PS003) that enhances the APC-cofactor activity of PS, showing an anti-thrombotic effect in a mouse model. This innovative approach might represent a promising and safe antithrombotic strategy.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Cardiac & Cardiovascular Systems
Xiaodan Zhong, Tao Wang, Yang Xie, Mengwen Wang, Wenjun Zhang, Lei Dai, Jinsheng Lai, Xiang Nie, Xingwei He, Thati Madhusudhan, Hesong Zeng, Hongjie Wang
Summary: This study demonstrates that aPC can protect against diabetic cardiomyopathy by maintaining YB-1 levels through the PAR1/EPCR signaling pathway, preventing its ubiquitination and degradation. Additionally, YB-1 exerts its protective effect by suppressing MEF2B transcription, highlighting the crucial role of the OTUB1/YB-1/MEF2B axis in diabetic cardiomyopathy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Meilang Xue, Haiyan Lin, Ruilong Zhao, Callum Fryer, Lyn March, Christopher J. Jackson
Summary: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by excessive inflammation and compromised skin barrier function. Activated protein C (APC) has therapeutic potential for AD due to its anti-inflammatory and barrier protective properties. APC exerts its effects through inhibition of protease activated receptor (PAR)2, while PAR1 has limited impact on inflammation in AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Critical Care Medicine
Florian Furrer, Pedro David Wendel-Garcia, Pablo Pfister, Daniel Andrea Hofmaenner, Carlos Franco, Alexandra Sachs, Juliane Fleischer, Christian Both, Bong Sun Kim, Reto A. Schuepbach, Peter Steiger, Giovanni Camen, Philipp Karl Buehler
Summary: This study investigated the intraoperative warming effect of oesophageal heat transfer in severe burn patients. The use of an oesophageal heat transfer device was found to be effective and safe in providing perioperative warming, potentially reducing hypothermia-associated complications in severely burned patients.
Article
Medicine, Research & Experimental
Charles P. Hinzman, Meth Jayatilake, Sunil Bansal, Brian L. Fish, Yaoxiang Li, Yubo Zhang, Shivani Bansal, Michael Girgis, Anton Iliuk, Xiao Xu, Jose A. Fernandez, John H. Griffin, Elizabeth A. Ballew, Keith Unger, Marjan Boerma, Meetha Medhora, Amrita K. Cheema
Summary: This study compares and optimizes methods for isolation and analysis of extracellular vesicles (EVs) from small volumes of urine. The size-exclusion chromatography method is found to be the preferred method for EV isolation. Mass spectrometry analysis of EV cargo reveals radiation-induced changes in nucleotide, folate, and lipid metabolism. These findings have important implications for monitoring response to radiotherapy and other molecular phenotyping studies.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Health Care Sciences & Services
Quentin Lohmeyer, Cornel Schiess, Pedro David Wendel Garcia, Heidi Petry, Eric Strauch, Andreas Dietsche, Reto A. Schuepbach, Philipp K. Buehler, Daniel A. Hofmaenner
Summary: This study found that using "tall man" lettering (TML) coding on syringe labels can reduce the error rate and change the visual attention of critical care nurses, thus helping to prevent medication errors.
BMJ QUALITY & SAFETY
(2023)
Article
Biochemistry & Molecular Biology
Idoia Busnadiego, Irene A. Abela, Pascal M. Frey, Daniel A. Hofmaenner, Thomas C. Scheier, Reto A. Schuepbach, Philipp K. Buehler, Silvio D. Brugger, Benjamin G. Hale
Summary: Autoantibodies neutralizing the antiviral action of type I interferons have been found in critically ill COVID-19 patients, and these antibodies may be associated with the occurrence of herpesvirus diseases.
Article
Medicine, General & Internal
Simona Humbel, Pedro David Wendel-Garcia, Simone Unseld, Fabienne Noll, Reto Andreas Schuepbach, Christoph Camille Ganter, Harald Seeger, Sascha David, Rea Andermatt
Summary: This study analyzed the clinical course of metabolic acidosis in critically ill pregnant COVID-19 patients, finding it to be common with some patients meeting diagnostic criteria for RTA. All patients recovered spontaneously within less than 7 days.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Bala Mohan Sivani, Mahmoud Azzeh, Rajashree Patnaik, Anca Pantea Stoian, Manfredi Rizzo, Yajnavalka Banerjee
Summary: This review critically appraises the pharmacological properties of curcumin, focusing on its antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. Various extraction strategies and clinical trials are also reviewed. The review highlights the need for further research in specific areas.
Review
Biochemistry & Molecular Biology
Giuseppe Mainas, Luigi Nibali, Mark Ide, Wael Al Mahmeed, Khalid Al-Rasadi, Kamila Al-Alawi, Maciej Banach, Yajnavalka Banerjee, Antonio Ceriello, Mustafa Cesur, Francesco Cosentino, Alberto Firenze, Massimo Galia, Su-Yen Goh, Andrej Janez, Sanjay Kalra, Nitin Kapoor, Peter Kempler, Nader Lessan, Paulo Lotufo, Nikolaos Papanas, Ali A. Rizvi, Amirhossein Sahebkar, Raul D. Santos, Anca P. Stoian, Peter P. Toth, Vijay Viswanathan, Manfredi Rizzo
Summary: Periodontitis is a disease that leads to the loss of periodontal attachment and bone resorption. COVID-19 is a contagious disease caused by SARS-CoV-2. Investigations have shown a possible relationship between periodontitis and COVID-19, as both conditions can lead to cardiometabolic impairments. This review aims to summarize the existing evidence regarding the link between periodontitis and COVID-19 and their associated complications.
Article
Hematology
Derek S. Sim, Meenal Shukla, Cornell R. Mallari, Jose A. Fernandez, Xiao Xu, Doug Schneider, Maxine Bauzon, Terry W. Hermiston, Laurent O. Mosnier
Summary: Activated protein C (APC) is a multifunctional coagulation protease with anticoagulant, antiinflammatory, and cytoprotective activities. Through selective modulation of APC activities, therapeutics can be developed for pathologies associated with these mechanisms. Identification of nanobodies that selectively recognize APC has provided insights into the diversity of APC functions and their potential therapeutic applications. LP11, in particular, has been found to selectively modulate APC anticoagulation and PAR1 cleavage, suggesting its potential in promoting hemostasis and cytoprotection in bleeding disorders.
Article
Hematology
Steven P. Grover, Vanthana Bharathi, Jens J. Posma, John H. Griffin, Joseph S. Palumbo, Nigel Mackman, Silvio Antoniak
Summary: The chemotherapeutic drug doxorubicin is cardiotoxic and can cause irreversible heart failure. In addition, it induces the activation of coagulation. Thrombin-mediated activation of protease-activated receptor 1 (PAR1) has been found to contribute to doxorubicin-induced cardiac injury.
Article
Biology
Shivani Bansal, Sunil Bansal, Brian L. Fish, Yaoxiang Li, Xiao Xu, Jose A. Fernandez, John H. Griffin, Heather A. Himburg, Marjan Boerma, Meetha Medhora, Amrita K. Cheema
Summary: The purpose of this study was to investigate longitudinal changes in urinary metabolites after IR exposure and explore the potential alleviation of radiation toxicities through the administration of recombinant APC. Female adult WAG/RijCmcr rats were irradiated and urine samples were collected for LC-MS metabolomics analysis. Different forms of APC were administered to sub-cohorts of rats and the results showed that radiation induced significant changes in urinary profiles, and treatment with rat wildtype-APC or rat 3K3A-APC could alleviate radiation-induced metabolic alterations to some extent.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yaoxiang Li, Shivani Bansal, Vijayalakshmi Sridharan, Sunil Bansal, Meth M. Jayatilake, Jose A. Fernandez, John H. Griffin, Marjan Boerma, Amrita K. Cheema
Summary: In this study, the researchers aimed to identify urinary metabolites that can indicate radiation-induced cardiac damage. They analyzed previously collected urine samples and found that radiation caused disturbances in various metabolic pathways, with wild-type mice showing more prominent effects than APCHi mice. By combining genotype and sex, the researchers identified a urinary biomarker panel that can predict heart dysfunction. It is important to note that this study did not use live mice but focused on analyzing previously collected urine samples.
Article
Health Care Sciences & Services
Farah Otaki, Mandana Gholami, Iman Fawad, Anjum Akbar, Yajnavalka Banerjee
Summary: This study aims to develop and evaluate a problem-solving assessment as an instructional tool for a biochemistry course in a medical program. The results will provide evidence for the application of this assessment in achieving competency goals and fostering self-directed learning, which can be beneficial to other medical educators in similar contexts.
JMIR RESEARCH PROTOCOLS
(2023)
Article
Health Care Sciences & Services
Rajashree Patnaik, Shirin Jannati, Bala Mohan Sivani, Manfredi Rizzo, Nerissa Naidoo, Yajnavalka Banerjee
Summary: This study developed a novel protocol for generating chondrocytes from bone marrow-derived mesenchymal stem cells (BMSCs) in a 3D culture system, which has significant implications for cartilage biology research and the discovery of potential therapeutic interventions.
JMIR RESEARCH PROTOCOLS
(2023)
Letter
Hematology
Swati Sharma, Lauryn T. Ursery, Vanthana Bharathi, Stephen D. Miles, Willie A. Williams, Aymen Z. Elzawam, Clare M. Schmedes, Grant J. Egnatz, Jose A. Fernandez, Joseph S. Palumbo, John H. Grif, Nigel Mackman, Silvio Antoniak
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)