1,690 results match your criteria pathway discoveries

Classification and Treatment of Diseases in the Age of Genome Medicine Based on Pathway Pathology.

Iver Petersen

Int J Mol Sci 2021 Aug 30;22(17). Epub 2021 Aug 30.

Institute of Pathology, SRH Poliklinik Gera, SRH-Wald-Klinikum Gera, Strasse des Friedens 122, D-07548 Gera, Germany.

The focus of pathology as a biomedical discipline is the identification of the pathomechanisms of diseases and the integration of this knowledge into routine diagnosis and classification. Standard tools are macroscopic and microscopic analysis complemented by immunohistochemistry and molecular pathology. So far, classification has been based on the paradigm of cellular pathology established by Rudolf Virchow and others more than 150 years ago, stating that diseases originate from diseased cells. Read More

View Article and Full-Text PDF

Mechanisms underlying host defense and disease pathology in response to severe acute respiratory syndrome (SARS)-CoV2 infection: insights from inborn errors of immunity.

Curr Opin Allergy Clin Immunol 2021 Sep 7. Epub 2021 Sep 7.

Garvan Institute of Medical Research, Darlinghurst St Vincent's Clinical School, UNSW Sydney, Randwick, New South Wales, Australia Laboratory of Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven Childhood Immunology, Department of Pediatrics, UZ Leuven, Leuven, Belgium.

Purpose Of Review: The severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV2)/COVID-19 pandemic has reminded us of the fundamental and nonredundant role played by the innate and adaptive immune systems in host defense against emerging pathogens. The study of rare 'experiments of nature' in the setting of inborn errors of immunity (IEI) caused by monogenic germline variants has revealed key insights into the molecular and cellular requirements for immune-mediated protection against infectious diseases. This review will provide an overview of the discoveries obtained from investigating severe COVID-19 in patients with defined IEI or otherwise healthy individuals. Read More

View Article and Full-Text PDF
September 2021

Cancer testis antigens and genomic instability: More than immunology.

DNA Repair (Amst) 2021 Aug 17;108:103214. Epub 2021 Aug 17.

Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, 95616-8665, USA; Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, 95616-8665, USA. Electronic address:

Cancer testis antigens or genes (CTA, CTG) are predominantly expressed in adult testes while silenced in most or all somatic tissues with sporadic expression in many human cancers. Concerted misexpression of numerous CTA/CTGs is rarely observed. This finding argues against the germ cell theory of cancer. Read More

View Article and Full-Text PDF

PIK3CA mutations in plasma circulating tumor DNA predict survival and treatment outcomes in patients with advanced cancers.

ESMO Open 2021 Aug 31;6(5):100230. Epub 2021 Aug 31.

Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address:

Background: Oncogenic mutations in PIK3CA are prevalent in diverse cancers and can be targeted with inhibitors of the phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Analysis of circulating tumor DNA (ctDNA) provides a minimally invasive approach to detect clinically actionable PIK3CA mutations.

Patients And Methods: We analyzed PIK3CA hotspot mutation frequency by droplet digital PCR (QX 200; BioRad) using 16 ng of unamplified plasma-derived cell-free DNA from 68 patients with advanced solid tumors (breast cancer, n = 41; colorectal cancer, n = 13; other tumor types, n = 14). Read More

View Article and Full-Text PDF

Insights Into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy.

Curr Heart Fail Rep 2021 Sep 3. Epub 2021 Sep 3.

Heart and Diabetes Center NRW, Erich and Hanna Klessmann Institute, University Hospital of the Ruhr-University Bochum, Georgstrasse 11, 32545, Bad Oeynhausen, Germany.

Purpose Of Review: Arrhythmogenic cardiomyopathy (ACM) is a genetic disease characterized by life-threatening ventricular arrhythmias and sudden cardiac death (SCD) in apparently healthy young adults. Mutations in genes encoding for cellular junctions can be found in about half of the patients. However, disease onset and severity, risk of arrhythmias, and outcome are highly variable and drug-targeted treatment is currently unavailable. Read More

View Article and Full-Text PDF
September 2021

Retrospective Case Series Analysis of Family Alterations in Pancreatic Cancer: Real-World Outcomes From Targeted and Standard Therapies.

JCO Precis Oncol 2021 25;5. Epub 2021 Aug 25.

Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: In pancreatic cancer (PC), the family alterations define a rare subset of patients that may predict response to inhibition of the signaling pathway. A comprehensive understanding of the molecular and clinical characteristics of -mutated PC may support future development of -directed strategies.

Methods: Clinical outcomes were assessed across a multi-institutional case series of 81 patients with family-mutated PC. Read More

View Article and Full-Text PDF

The convoluted history of haem biosynthesis.

Biol Rev Camb Philos Soc 2021 Sep 2. Epub 2021 Sep 2.

Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branišovská 31, České Budějovice (Budweis), 370 05, Czech Republic.

The capacity of haem to transfer electrons, bind diatomic gases, and catalyse various biochemical reactions makes it one of the essential biomolecules on Earth and one that was likely used by the earliest forms of cellular life. Since the description of haem biosynthesis, our understanding of this multi-step pathway has been almost exclusively derived from a handful of model organisms from narrow taxonomic contexts. Recent advances in genome sequencing and functional studies of diverse and previously neglected groups have led to discoveries of alternative routes of haem biosynthesis that deviate from the 'classical' pathway. Read More

View Article and Full-Text PDF
September 2021

Degradation of WTAP blocks antiviral responses by reducing the m A levels of IRF3 and IFNAR1 mRNA.

EMBO Rep 2021 Sep 1:e52101. Epub 2021 Sep 1.

Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.

N -methyladenosine (m A) is a chemical modification present in multiple RNA species and is most abundant in mRNAs. Studies on m A reveal its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. Although some recent discoveries indicate that m A can affect the life cycles of numerous viruses as well as the cellular antiviral immune response, the roles of m A modification in type I interferon (IFN-I) signaling are still largely unknown. Read More

View Article and Full-Text PDF
September 2021

lncExplore: a database of pan-cancer analysis and systematic functional annotation for lncRNAs from RNA-sequencing data.

Database (Oxford) 2021 Aug;2021

Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, No.176, Chong-Hua Rd., Changhua 50046, Taiwan.

Over the past few years, with the rapid growth of deep-sequencing technology and the development of computational prediction algorithms, a large number of long non-coding RNAs (lncRNAs) have been identified in various types of human cancers. Therefore, it has become critical to determine how to properly annotate the potential function of lncRNAs from RNA-sequencing (RNA-seq) data and arrange the robust information and analysis into a useful system readily accessible by biological and clinical researchers. In order to produce a collective interpretation of lncRNA functions, it is necessary to integrate different types of data regarding the important functional diversity and regulatory role of these lncRNAs. Read More

View Article and Full-Text PDF

Applications of upconversion nanoparticles in cellular optogenetics.

Acta Biomater 2021 Aug 28. Epub 2021 Aug 28.

Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, State Key Laboratory of Modern Optical Instrumentation, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou 310027, China; Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China. Electronic address:

Upconversion-mediated optogenetics is an emerging powerful technique to remotely control and manipulate the deep-tissue protein functions and signaling pathway activation. This technique uses lanthanide upconversion nanoparticles (UCNPs) as light transducers and through near-infrared light to indirectly activate the traditional optogenetic proteins. With the merits of high spatiotemporal resolution and minimal invasiveness, this technique enables cell-type specific manipulation of cellular activities in deep tissues as well as in living animals. Read More

View Article and Full-Text PDF

Destruction or Reconstruction: A Subtle Liaison between the Proteolytic and Signaling Role of Protein Ubiquitination in Spermatogenesis.

Giovanna Berruti

Adv Exp Med Biol 2021 ;1288:215-240

Department of Bioscience, University of Milan, Milan, Italy.

Ubiquitination is one of the most diverse forms of protein post-translational modification that changes the function of the landscape of substrate proteins in response to stimuli, without the need for "de novo" protein synthesis. Ubiquitination is involved in almost all aspects of eukaryotic cell biology, from the best-studied role in promoting the removal of faulty or unnecessary proteins by the way of the ubiquitin proteasome system and autophagy-lysosome pathway to the recruitment of proteins in specific non-proteolytic signaling pathways, as emerged by the more recent discoveries about the protein signature with peculiar types of ubiquitin chains. Spermatogenesis, on its own, is a complex cellular developmental process in which mitosis, meiosis, and cell differentiation coexist so to result in the continuous formation of haploid spermatozoa. Read More

View Article and Full-Text PDF

An overview of the insulin signaling pathway in model organisms Drosophila melanogaster and Caenorhabditis elegans.

Peptides 2021 Aug 24;145:170640. Epub 2021 Aug 24.

Department of Biology, Queen's University Kingston, ON, K7L3N6, Canada.

The insulin/insulin-like growth factor signaling pathway is an evolutionary conserved pathway across metazoans and is required for development, metabolism and behavior. This pathway is associated with various human metabolic disorders and cancers. Thus, model organisms including Drosophila melanogaster and Caenorhabditis elegans provide excellent opportunities to examine the structure and function of this pathway and its influence on cellular metabolism and proliferation. Read More

View Article and Full-Text PDF

CDK4, CDK6/cyclin-D1 Complex Inhibition and Radiotherapy for Cancer Control: A Role for Autophagy.

Int J Mol Sci 2021 Aug 4;22(16). Epub 2021 Aug 4.

Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19104, USA.

The expanding clinical application of CDK4- and CDK6-inhibiting drugs in the managements of breast cancer has raised a great interest in testing these drugs in other neoplasms. The potential of combining these drugs with other therapeutic approaches seems to be an interesting work-ground to explore. Even though a potential integration of CDK4 and CDK6 inhibitors with radiotherapy (RT) has been hypothesized, this kind of approach has not been sufficiently pursued, neither in preclinical nor in clinical studies. Read More

View Article and Full-Text PDF

Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers.

Nat Commun 2021 08 20;12(1):5053. Epub 2021 Aug 20.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Previous studies have suggested that PTEN loss is associated with p110β signaling dependency, leading to the clinical development of p110β-selective inhibitors. Here we use a panel pre-clinical models to reveal that PI3K isoform dependency is not governed by loss of PTEN and is impacted by feedback inhibition and concurrent PIK3CA/PIK3CB alterations. Furthermore, while pan-PI3K inhibition in PTEN-deficient tumors is efficacious, upregulation of Insulin Like Growth Factor 1 Receptor (IGF1R) promotes resistance. Read More

View Article and Full-Text PDF

Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats.

Sci Rep 2021 Aug 11;11(1):16359. Epub 2021 Aug 11.

International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.

A better understanding of the secondary injury mechanisms that occur after traumatic spinal cord injury (SCI) is essential for the development of novel neuroprotective strategies linked to the restoration of metabolic deficits. We and others have shown that Ketogenic diet (KD), a high fat, moderate in proteins and low in carbohydrates is neuroprotective and improves behavioural outcomes in rats with acute SCI. Ketones are alternative fuels for mitochondrial ATP generation, and can modulate signaling pathways via targeting specific receptors. Read More

View Article and Full-Text PDF

Identification of a pathway for electron uptake in Shewanella oneidensis.

Commun Biol 2021 08 11;4(1):957. Epub 2021 Aug 11.

Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA.

Extracellular electron transfer (EET) could enable electron uptake into microbial metabolism for the synthesis of complex, energy dense organic molecules from CO and renewable electricity. Theoretically EET could do this with an efficiency comparable to H-oxidation but without the need for a volatile intermediate and the problems it causes for scale up. However, significant gaps remain in understanding the mechanism and genetics of electron uptake. Read More

View Article and Full-Text PDF

The MAVS Immune Recognition Pathway in Viral Infection and Sepsis.

Antioxid Redox Signal 2021 Aug 5. Epub 2021 Aug 5.

Boston University School of Medicine, 12259, Pulmonary Center, Department of Medicine, Boston, Massachusetts, United States.

Significance: It is estimated that close to 50 million cases of sepsis result in over 11 million annual fatalities worldwide. The pathognomonic feature of sepsis is a dysregulated inflammatory response arising from viral, bacterial, or fungal infections. Immune recognition of pathogen-associated molecular patterns (PAMPs) is a hallmark of the host immune defense to combat microbes and to prevent the progression to sepsis. Read More

View Article and Full-Text PDF

Screening for New Pathways in Atmospheric Oxidation Chemistry with Automated Mechanism Generation.

J Phys Chem A 2021 Aug 4;125(31):6772-6788. Epub 2021 Aug 4.

Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

In the Earth's atmosphere, reactive organic carbon undergoes oxidation via a highly complex, multigeneration process, with implications for air quality and climate. Decades of experimental and theoretical studies, primarily on the reactions of hydrocarbons, have led to a canonical understanding of how gas-phase oxidation of organic compounds takes place. Recent research has brought to light a number of examples where the presence of certain functional groups opens up reaction pathways for key radical intermediates, including alkyl radicals, alkoxy radicals, and peroxy radicals, that are substantially different from traditional oxidation mechanisms. Read More

View Article and Full-Text PDF

Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics.

Int J Nanomedicine 2021 26;16:5065-5098. Epub 2021 Jul 26.

Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.

The smart strategy of cancer cells to bypass the caspase-dependent apoptotic pathway has led to the discovery of novel anti-cancer approaches including the targeting of lysosomes. Recent discoveries observed that lysosomes perform far beyond just recycling of cellular waste, as these organelles are metabolically very active and mediate several signalling pathways to sense the cellular metabolic status. These organelles also play a significant role in mediating the immune system functions. Read More

View Article and Full-Text PDF

MiR156 regulates anthocyanin biosynthesis through SPL targets and other microRNAs in poplar.

Hortic Res 2020 Aug 1;7(1):118. Epub 2020 Aug 1.

Shandong Provincial Key Laboratory of Energy Genetics, Key Laboratory of Biofuels, Chinese Academy of Sciences, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, 266101, China.

Anthocyanins biosynthesized from the flavonoid pathway are types of pigments that are involved in the protection of poplar from biotic and abiotic stresses. Previous researchers studying anthocyanin-related transcription factors and structural genes in poplar have made significant discoveries. However, little is known about the regulatory role of microRNAs in anthocyanin biosynthesis in poplar. Read More

View Article and Full-Text PDF

EGR2-mediated regulation of mA reader IGF2BP proteins drive RCC tumorigenesis and metastasis via enhancing S1PR3 mRNA stabilization.

Cell Death Dis 2021 Jul 29;12(8):750. Epub 2021 Jul 29.

Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, 310000, Hangzhou, Zhejiang, China.

Emerging discoveries of dynamic and reversible N6-methyladenosine (mA) modification on RNA in mammals have revealed the key roles of the modification in human tumorigenesis. As known mA readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are upregulated in most cancers and mediates the enhancement of mA-modified mRNAs stability. However, the mechanisms of IGF2BPs in renal cell cancer (RCC) still remain unclear. Read More

View Article and Full-Text PDF

Auxin in Root Development.

Cold Spring Harb Perspect Biol 2021 Jul 26. Epub 2021 Jul 26.

Centre for Plant Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.

Root system architecture is an important determinant of below-ground resource capture and hence overall plant fitness. The plant hormone auxin plays a central role in almost every facet of root development from the cellular to the whole-root-system level. Here, using as a model, we review the multiple gene signaling networks regulated by auxin biosynthesis, conjugation, and transport that underpin primary and lateral root development. Read More

View Article and Full-Text PDF

TGF-β Signaling: From Tissue Fibrosis to Tumor Microenvironment.

Int J Mol Sci 2021 Jul 15;22(14). Epub 2021 Jul 15.

Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China.

Transforming growth factor-β (TGF-β) signaling triggers diverse biological actions in inflammatory diseases. In tissue fibrosis, it acts as a key pathogenic regulator for promoting immunoregulation via controlling the activation, proliferation, and apoptosis of immunocytes. In cancer, it plays a critical role in tumor microenvironment (TME) for accelerating invasion, metastasis, angiogenesis, and immunosuppression. Read More

View Article and Full-Text PDF

Regulation of Gene Expression by Amino Acids in Animal Cells.

Adv Exp Med Biol 2021 ;1332:1-15

Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA.

Amino acids have pleiotropic roles in animal biology including protein and glucose synthesis, cellular metabolism, antioxidant reactions, immune enhancers, and inducers or suppressors of gene expression. Recent studies have revealed important roles of amino acids in the regulation of gene expression in animals. Discoveries of cellular amino acid sensors and their mechanistic pathways have broadened our understanding of how the body responds to the deprivation of nutrients and amino acids in particular. Read More

View Article and Full-Text PDF

Bioinformatics analysis of differentially expressed genes and identification of an miRNA-mRNA network associated with entorhinal cortex and hippocampus in Alzheimer's disease.

Hereditas 2021 Jul 9;158(1):25. Epub 2021 Jul 9.

Department of Human Anatomy, Institute of Neurobiology, Medical School of Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, China.

Background: Alzheimer's disease (AD) is a fatal neurodegenerative disorder, and the lesions originate in the entorhinal cortex (EC) and hippocampus (HIP) at the early stage of AD progression. Gaining insight into the molecular mechanisms underlying AD is critical for the diagnosis and treatment of this disorder. Recent discoveries have uncovered the essential roles of microRNAs (miRNAs) in aging and have identified the potential of miRNAs serving as biomarkers in AD diagnosis. Read More

View Article and Full-Text PDF

The molecular mechanism of LRP1 in physiological vascular homeostasis and signal transduction pathways.

Biomed Pharmacother 2021 Jul 7;139:111667. Epub 2021 May 7.

Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Reseach Center, Southwest Medical University, 319 Zhongshan Road, Luzhou, Sichuan 646000, China; Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, the School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. Electronic address:

Interactions between vascular smooth muscle cells (VSMCs), endothelial cells (ECs), pericytes (PCs) and macrophages (MФ), the major components of blood vessels, play a crucial role in maintaining vascular structural and functional homeostasis. Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1), a transmembrane receptor protein belonging to the LDL receptor family, plays multifunctional roles in maintaining endocytosis, homeostasis, and signal transduction. Accumulating evidence suggests that LRP1 modulates vascular homeostasis mainly by regulating vasoactive substances and specific intracellular signaling pathways, including the plasminogen activator inhibitor 1 (PAI-1) signaling pathway, platelet-derived growth factor (PDGF) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway. Read More

View Article and Full-Text PDF

A randomized double blinded placebo controlled study to evaluate motor unit abnormalities after experimentally induced sensitization using capsaicin.

Sci Rep 2021 Jul 2;11(1):13793. Epub 2021 Jul 2.

Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada.

Central sensitization is a condition that represents a cascade of neurological adaptations, resulting in an amplification of nociceptive responses from noxious and non-noxious stimuli. However, whether this abnormality translates into motor output and more specifically, ventral horn abnormalities, needs to be further explored. Twenty healthy participants aged 20-70 were randomly allocated to topical capsaicin or a placebo topical cream which was applied onto their left upper back to induce a transient state of sensitization. Read More

View Article and Full-Text PDF

Interplay of cGAS with chromatin.

Trends Biochem Sci 2021 Oct 29;46(10):822-831. Epub 2021 Jun 29.

Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address:

Recognition of DNA is an evolutionarily highly conserved mechanism of immunity. In mammals, the cGAS-STING pathway plays a central role in coupling DNA sensing to the execution of innate immune mechanisms, both in contexts of infection as well as in noninfectious settings of cellular stress and injury. The indiscriminate ability of double-stranded DNA (dsDNA) to activate cGAS challenges our understanding on how engagement of this pathway is prevented on genomic self-DNA under homeostatic conditions. Read More

View Article and Full-Text PDF
October 2021

mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss.

Int J Mol Sci 2021 Jun 14;22(12). Epub 2021 Jun 14.

Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.

Hearing loss affects many people worldwide and occurs often as a result of age, ototoxic drugs and/or excessive noise exposure. With a growing number of elderly people, the number of people suffering from hearing loss will also increase in the future. Despite the high number of affected people, for most patients there is no curative therapy for hearing loss and hearing aids or cochlea implants remain the only option. Read More

View Article and Full-Text PDF

cGAS-STING: insight on the evolution of a primordial antiviral signaling cassette.

Fac Rev 2021 8;10:54. Epub 2021 Jun 8.

Sino-French Hoffmann Institute, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.

Stimulator of interferon genes (STING) functions in the cytosolic DNA-sensing pathway of innate immunity in mammals. It is activated upon binding the cyclic dinucleotide 2'3'-cGAMP, a second messenger produced by the enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), which acts as the receptor for DNA in this pathway, and triggers the expression of interferons and other viral stress-induced genes. The ancient origin of STING in the evolution of animals had been noted, but its primitive function was speculative. Read More

View Article and Full-Text PDF