Article
Geriatrics & Gerontology
Yu Cao, Yang Fan, Fangyuan Li, Yu Hao, Yaxian Kong, Chen Chen, Xing Hao, Dannuo Han, Guoli Li, Zengtao Wang, Chuan Song, Junyan Han, Hui Zeng
Summary: Circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.
Article
Engineering, Environmental
Liping Pang, Susan Lin, Aruni Premaratne, Annabelle Tham, Phillip Abraham, Chris Nokes
Summary: Point-of-use filters are commonly used in developing communities to treat household drinking water, with activated carbon filters proving more effective than other types in removing protozoa. Additional treatment such as water boiling or ultraviolet disinfection is necessary when using other filter types to meet protozoan removal requirements.
JOURNAL OF WATER PROCESS ENGINEERING
(2021)
Article
Infectious Diseases
Pasa Sukson, Chalerm Liwsrisakun, Juthamas Inchai, Konlawij Trongtrakul, Pattraporn Tajarernmuang
Summary: The peripheral monocyte to lymphocyte ratio (ML ratio) is a useful tool for diagnosing and predicting treatment response in patients with tuberculous pleuritis, showing potential as an adjunctive diagnostic and monitoring tool.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Oncology
Lucy Wanjiku Macharia, Wanjiru Muriithi, Carlos Pilotto Heming, Dennis Kirii Nyaga, Veronica Aran, Marianne Wanjiru Mureithi, Valeria Pereira Ferrer, Attilio Pane, Paulo Niemeyer Filho, Vivaldo Moura-Neto
Summary: This study reveals that miRNAs are dysregulated, stemness factors are induced, and alteration of survival genes occurs in GBM cells when exposed to a hypoxic tumor microenvironment, potentially contributing to GBM aggressiveness.
Article
Biochemistry & Molecular Biology
Srinivas Akula, Sandra Lara, Anna-Karin Olsson, Lars Hellman
Summary: The commonly used human monocyte/macrophage cell lines Mono Mac 6 and THP-1 exhibit a very immature phenotype, resembling immature neutrophils rather than mature monocytes/macrophages. Therefore, caution should be taken when using these cell lines as models for normal monocyte/macrophage biology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Bryce Dylan Schubert, Heng Ku, Mwila Kabwe, Trang Hong Nguyen, Helen Irving, Joseph Tucci
Summary: Bacterial sepsis, characterized by immunosuppression and cytokine storm, is difficult to treat clinically. The role of bacteriophages in immune modulation of sepsis is unclear. In this study, we isolated two lytic bacteriophages against K. pneumoniae that cause sepsis in humans, one of which was a novel jumbo bacteriophage. We demonstrated for the first time that these bacteriophages did not stimulate excessive production of tumor necrosis factor alpha or interleukin-6 in THP-1 monocyte cell lines with varying levels of IRAK3 expression.
Article
Urology & Nephrology
Daniel J. Cooper, Katherine Plewes, Matthew J. Grigg, Aatish Patel, Giri S. Rajahram, Timothy William, Thomas F. Hiemstra, Zhiqiang Wang, Bridget E. Barber, Nicholas M. Anstey
Summary: The study found that equations using an assumed glomerular filtration rate (GFR) of 75 ml/min underestimated the incidence of AKI in studies of acute infection. Back-calculation with the CKD-EPI equation and an assumed GFR of 100 ml/min most accurately predicted AKI but misclassified all AKI stages and had low levels of agreement with true AKI diagnoses.
KIDNEY INTERNATIONAL REPORTS
(2021)
Article
Endocrinology & Metabolism
Paulina Carmona-Mora, Bradley P. Ander, Glen C. Jickling, Cheryl Dykstra-Aiello, Xinhua Zhan, Eva Ferino, Farah Hamade, Hajar Amini, Heather Hull, Frank R. Sharp, Boryana Stamova
Summary: In both IS and ICH, monocyte genes were down-regulated, whereas neutrophil gene expression changes were generally up-regulated. The monocyte down-regulated response to ICH included innate, adaptive immune, dendritic, NK cell and atherosclerosis signaling. Neutrophil responses to ICH included tRNA charging, mitochondrial dysfunction, and ER stress pathways. Common monocyte and neutrophil responses to ICH included interferon signaling, neuroinflammation, death receptor signaling, and NFAT pathways.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Cardiac & Cardiovascular Systems
Aiko Saku, Tomoyuki Fujisawa, Koji Nishimoto, Katsuhiro Yoshimura, Hironao Hozumi, Masato Karayama, Yuzo Suzuki, Kazuki Furuhashi, Noriyuki Enomoto, Yutaro Nakamura, Naoki Inui, Takafumi Suda
Summary: This study retrospectively reviewed medical records of 72 patients with RA-ILD and found that increased peripheral monocyte count was significantly associated with poor prognosis. Patients with high monocyte and neutrophil counts had lower survival rates, suggesting their potential as cellular biomarkers to predict outcomes in RA-ILD patients.
RESPIRATORY MEDICINE
(2021)
Article
Medicine, Research & Experimental
Vincent Jachiet, Laure Ricard, Pierre Hirsch, Florent Malard, Laurent Pascal, Odile Beyne-Rauzy, Pierre Peterlin, Alexandre Thibault Jacques Maria, Norbert Vey, Maud D'Aveni, Marie-Pierre Gourin, Sophie Dimicoli-Salazar, Anne Banos, Stefan Wickenhauser, Louis Terriou, Benoit De Renzis, Eric Durot, Shanti Natarajan-Ame, Anne Vekhoff, Laurent Voillat, Sophie Park, Julien Vinit, Celine Dieval, Azeddine Dellal, Vincent Grobost, Lise Willems, Julien Rossignol, Eric Solary, Olivier Kosmider, Nicolas Dulphy, Lin Pierre Zhao, Lionel Ades, Pierre Fenaux, Olivier Fain, Mohamad Mohty, Beatrice Gaugler, Arsene Mekinian
Summary: Background systemic inflammatory and autoimmune diseases (SIADs) occur in a significant proportion of myelodysplastic syndrome (MDS) patients. The recently identified VEXAS syndrome, associated with somatic mutations in UBA1, is characterized by severe inflammatory conditions and hematological abnormalities, including MDS. However, the mechanisms underlying the association between MDS and SIADs are largely unknown. This study aimed to evaluate myeloid immune cell subsets in MDS patients with and without SIAD and compare them to healthy controls.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Wanjing Cen, Felix Umrath, Antonio Jose Salgado, Siegmar Reinert, Dorothea Alexander
Summary: The secretomes derived from osteogenically induced jaw periosteum-derived mesenchymal stem cells (JPCs) have inhibitory effects on the maturation of monocyte-derived dendritic cells (MoDCs), as they reduce the formation of MoDC clusters and down-regulate the expression of CD80, CD86, and CD197 on MoDCs. The secretomes also enhance the uptake capacity of MoDCs and promote the expansion of regulatory T cells. Furthermore, the secretomes affect the gene expression of MoDCs, up-regulating CD209, HLA-DRA, CSF3, IL10, and IL8, and down-regulating IFN gamma and IL12B.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Agronomy
Baicui Wang, Xiaolan Ma, Xingguo Ye, Yilin Zhou, Youzhi Ma, Zhishan Lin
Summary: The study found that wheat-Dasypyrum villosum translocation lines have similar base composition characteristics to common wheat parents, but the genotypes on the translocation chromosomes are more heterozygous. The distribution of SNPs between the translocation lines and Wan7107 is mainly concentrated in the regions of 6AS or 6DS, with some unexpected presence near the telomere of 2BS and other wheat chromosomes. In addition, the translocation lines A303 and B303 have identical genotypes with Wan7107 up to 99.44% and 98.81%, respectively.
Article
Geriatrics & Gerontology
Akia Dawson, Tyler Brown, Juzer Ali Asgar, Alana Keegan, Christopher R. D'Adamo, Jasmine Demos, Joanne Coleman, Mark Katlic, Arun Mavanur, Joshua H. Wolf
Summary: This study evaluated the relationship between the simplified frailty index (sFI) and phenotypic frailty. The results showed a significant but modest inverse correlation between sFI and phenotypic frailty, indicating that sFI may not be suitable for assessing postoperative complications related to cognition.
ARCHIVES OF GERONTOLOGY AND GERIATRICS
(2023)
Article
Plant Sciences
Fabrizio Olivieri, Salvatore Graci, Silvana Francesca, Maria Manuela Rigano, Amalia Barone
Summary: Constructing heat-tolerant F-1 hybrids is crucial for ensuring high yield and fruit quality in global climate challenges. Through evaluating genotypes and conducting molecular marker analysis, potential resistance genes were identified for further investigation. Thirteen F-1 hybrids were developed, with seven showing the best performances in terms of yield, fruit quality, and disease resistance under high temperature conditions.
Article
Oncology
Anna-Maja Aberg, Sofia Halin Bergstrom, Elin Thysell, Lee-Ann Tjon-Kon-Fat, Jonas A. Nilsson, Anders Widmark, Camilla Thellenberg-Karlsson, Anders Bergh, Pernilla Wikstrom, Marie Lundholm
Summary: This study found that high levels of monocytes, S100A9, and S100A12 in prostate cancer patients were associated with poor outcomes, particularly in those with metastases at diagnosis.
Article
Pharmacology & Pharmacy
Jon Merlin, Julia Park, Teresa H. Vandekolk, Stewart A. Fabb, Jeanne Allinne, Roger J. Summers, Christopher J. Langmead, Darren M. Riddy
Summary: This study comprehensively shows how several natural mediators and synthetic ligands signal through three specialized proresolving mediator GPCRs using multiple ligands from different classes across four-six endpoint signaling assays. The potential of these receptors in treating specific autoimmune diseases, including rheumatoid arthritis, systemic scleroderma, and systemic lupus erythennatosus, is highlighted.
MOLECULAR PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Brian P. Cary, Giuseppe Deganutti, Peishen Zhao, Tin T. Truong, Sarah J. Piper, Xinyu Liu, Matthew J. Belousoff, Radostin Danev, Patrick M. Sexton, Denise Wootten, Samuel H. Gellman
Summary: Recent advances in understanding the structures of G-protein-coupled receptors (GPCRs) have highlighted the importance of conformational flexibility in signal propagation. By studying the activation of the GLP-1 receptor, it was found that the conformational plasticity of peptide agonists plays a crucial role in determining agonist efficacy.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Peishen Zhao, Tin T. Truong, Jon Merlin, Patrick M. Sexton, Denise Wootten
Summary: This study investigates the kinetics of GLP-1R activation and cAMP production mediated by peptide agonists. The results reveal a positive correlation between peptide agonist dissociation kinetics and the onset, duration, and conformational change of receptor-G protein coupling and cAMP signaling. These findings advance the understanding of molecular events that link GLP-1R ligand binding to intracellular signaling and have implications for the agonist action at other related class B1 GPCRs.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sabrina N. Rahman, Daniel A. McNaught-Flores, Yara Huppelschoten, Daniel da Costa Pereira, Arthur Christopoulos, Rob Leurs, Christopher J. Langmead
Summary: The human histamine H3 receptor is expressed in the CNS and regulates the synthesis and release of histamine and neurotransmitters. It is associated with CNS disorders and its isoforms display variations in intracellular loop 3. The mechanisms of biased agonism at these isoforms remain unknown.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Huong T. M. Nguyen, Emma T. van der Westhuizen, Christopher J. Langmead, Andrew B. Tobin, Patrick M. Sexton, Arthur Christopoulos, Celine Valant
Summary: This review focuses on the drug discovery of M-1 receptor for the treatment of Alzheimer's disease and schizophrenia. Despite some progress, only a few drugs have reached clinical trials due to cholinergic adverse effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Endocrinology & Metabolism
Brian P. Cary, Xin Zhang, Jianjun Cao, Rachel M. Johnson, Sarah J. Piper, Elliot J. Gerrard, Denise Wootten, Patrick M. Sexton
Summary: G protein-coupled receptors (GPCRs), particularly the B1 class, play a critical role in maintaining homeostasis and are important drug targets. Recent advances in cryo-electron microscopy have provided valuable insights into the structure and dynamics of these receptors, which contribute to our understanding of their functions.
Review
Pharmacology & Pharmacy
Leigh C. Walker, Kade L. Huckstep, Howard C. Becker, Christopher J. Langmead, Andrew J. Lawrence
Summary: Emerging evidence suggests muscarinic acetylcholine receptors are potential targets for treating alcohol use disorder. This review integrates findings from medicinal chemistry, molecular biology, addiction, and learning/cognition fields to explore the potential of muscarinic receptor ligands in treating cognitive dysfunction, motivation to consume alcohol, and relapse associated with alcohol use disorder. The dysfunctional role of cholinergic system in alcohol use disorder is discussed, along with the potential therapeutic targets of specific muscarinic receptors, particularly M-4 and M-5 receptors. The use of subtype-selective allosteric modulators is proposed as a strategy to target these receptors, and the potential repurposing of muscarinic receptor modulators for alcohol use disorder is highlighted.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Correction
Biochemistry & Molecular Biology
Alexander S. Powers, Vi Pham, Wessel A. C. Burger, Geoff Thompson, Yianni Laloudakis, Nicholas W. Barnes, Patrick M. Sexton, Steven M. Paul, Arthur Christopoulos, David M. Thal, Christian C. Felder, Celine Valant, Ron O. Dror
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexander S. Powers, Vi Pham, Wessel A. C. Burger, Geoff Thompson, Yianni Laloudakis, Patrick M. Sexton, Steven M. Paul, Arthur Christopoulos, David M. Thal, Christian C. Felder, Celine Valant, Ron O. Dror
Summary: The selectivity of a drug for target receptors is crucial but challenging when the receptors are similar. Serendipitous discovery of ligands that stimulate target receptors more strongly than closely related receptors provides a solution. This study reveals the structural basis for the efficacy-driven selectivity of xanomeline, a clinical drug candidate, between closely related muscarinic acetylcholine receptors (mAChRs), using atomic-level simulations. The results suggest strategies for rational design of ligands achieving efficacy-driven selectivity for G-protein-coupled receptors.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Maleesha Ubhayarathna, Christopher J. Langmead, Natalie A. Diepenhorst, Gregory D. Stewart
Summary: Substance use disorder is a chronic condition with limited treatment options. The serotonin 2C receptor shows potential for the treatment of SUD, and research on psychedelics has also focused on this receptor. New studies provide a basis for further exploration.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Yao Lu, Cassandra J. Hatzipantelis, Christopher J. Langmead, Gregory D. Stewart
Summary: Schizophrenia treatment currently relies on outdated science, and targeting dopamine receptors has limited efficacy and side effects. Non-dopaminergic GPCR-targeting drugs show promise but have not yet been successfully developed for clinical use. Recent attention has focused on non-dopaminergic GPCR-targeting drugs, which have demonstrated efficacy in certain symptoms of schizophrenia.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Wessel A. C. Burger, Vi Pham, Ziva Vuckovic, Alexander S. Powers, Jesse I. Mobbs, Yianni Laloudakis, Alisa Glukhova, Denise Wootten, Andrew B. Tobin, Patrick M. Sexton, Steven M. Paul, Christian C. Felder, Radostin Danev, Ron O. Dror, Arthur Christopoulos, Celine Valant, David M. Thal
Summary: The M4 muscarinic acetylcholine receptor is a significant drug target for the treatment of psychosis, cognition, and addiction. The clinical trial of xanomeline has shown promise in improving symptoms and the cryo-EM structure reveals the binding mechanism, providing insight into its complex pharmacology.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Neurosciences
Wessel A. C. Burger, Vi Pham, Alexander Powers, Ziva Vuckovic, Jesse I. Mobbs, Alisa Glukhova, Denise Wootten, Andrew B. Tobin, Patrick M. Sexton, Steven M. Paul, Christian Felder, Radostin Danev, Arthur Christopoulos, Ron O. Dror, Celine Valant, David M. Thal
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Pramod C. Nair, Justin M. Chalker, Ross A. McKinnon, Christopher J. Langmead, Karen J. Gregory, Tarun Bastiampillai
Summary: Schizophrenia is a complex and severe mental illness. Current treatments primarily target dopamine neurotransmission and have limited effects on negative symptoms and cognitive impairments. Recent research on trace amine associated receptor-1 (TAAR1) suggests it may be a promising nondopaminergic target for treating schizophrenia and related disorders, with fewer side effects.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)