Viral Exposure Signature Associated with Liver Cancer Risk.
Abstract Virus infection is known to increase the risk of various cancers, including hepatocellular carcinoma (HCC). In a recent article in Cell, Liu et al. report a blood-based viral exposure signature (VES) based on a synthetic human virome to capture the history of virus exposure that is associated with future HCC occurrence. PMID: 32654969 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - July 10, 2020 Category: Molecular Biology Authors: Fujiwara N, Hoshida Y Tags: Trends Mol Med Source Type: research

Inflammasomes and Cell Death: Common Pathways in Microparticle Diseases.
Abstract The accumulation of cellular and environmental microparticles has been linked to many diseases associated with tissue inflammation. These particulate-driven diseases include joint, lung, kidney, cardiovascular, and neurodegenerative disorders. Recently a conserved proinflammatory inflammasome signaling pathway elicited by such microparticles has become apparent. Here, we review disease-promoting microparticles and the mechanisms by which they trigger activation of the inflammasome complexes responsible for generating bioactive interleukin-1β (IL-1β) and inducing cell death. We highlight how micr...
Source: Trends in Molecular Medicine - July 6, 2020 Category: Molecular Biology Authors: Rashidi M, Wicks IP, Vince JE Tags: Trends Mol Med Source Type: research

JAK-STAT Targeting Offers Novel Therapeutic Opportunities in Sepsis.
Abstract Sepsis is a life-threatening condition caused by exaggerated host responses to infections taking place in two phases: (i) a systemic (hyper)inflammatory response syndrome (SIRS), participating in multiple organ failure (MOF), a major complication of septic shock, followed by (ii) a compensatory anti-inflammatory response syndrome (CARS), leading to sepsis-induced immunosuppression and resulting in late infections and long-term mortality. The Janus kinase-signal transducer and activator of transcription (JAK-STAT)-dependent signaling pathway is involved in both manifestations, hence playing a key role duri...
Source: Trends in Molecular Medicine - July 3, 2020 Category: Molecular Biology Authors: Clere-Jehl R, Mariotte A, Meziani F, Bahram S, Georgel P, Helms J Tags: Trends Mol Med Source Type: research

Reducing Senescent Cell Burden in Aging and Disease.
Abstract Cellular senescence is a primary aging process and tumor suppressive mechanism characterized by irreversible growth arrest, apoptosis resistance, production of a senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, and alterations in DNA and chromatin. In preclinical aging models, accumulation of senescent cells is associated with multiple chronic diseases and disorders, geriatric syndromes, multimorbidity, and accelerated aging phenotypes. In animals, genetic and pharmacologic reduction of senescent cell burden results in the prevention, delay, and/or alleviation of a variety of a...
Source: Trends in Molecular Medicine - June 28, 2020 Category: Molecular Biology Authors: Pignolo RJ, Passos JF, Khosla S, Tchkonia T, Kirkland JL Tags: Trends Mol Med Source Type: research

Priming the Proteasome to Protect against Proteotoxicity.
Abstract Increased proteotoxic stress (IPTS) resulting from the increased production or decreased removal of abnormally folded proteins is recognized as an important pathogenic factor for a large group of highly disabling and life-threatening human diseases, such as neurodegenerative disorders and many heart diseases. The proteasome is pivotal to the timely removal of abnormal proteins but its functional capacity often becomes inadequate in the disease conditions; consequently, proteasome functional insufficiency in return exacerbates IPTS. Recent research in proteasome biology reveals that the proteasome can be a...
Source: Trends in Molecular Medicine - June 28, 2020 Category: Molecular Biology Authors: Wang X, Wang H Tags: Trends Mol Med Source Type: research

Bacterial Peptidoglycan as a Driver of Chronic Brain Inflammation.
Abstract Peptidoglycan (PGN) is a cell wall component of both Gram-positive and Gram-negative bacteria. Signature fragments of PGN are proinflammatory through engagement of pattern recognition receptors (PRR) on resident tissue cells and circulating leukocytes. Despite its abundance in the gut microbiota, there is limited recognition that PGN could contribute to chronic neuroinflammation. This review highlights current insights into the roles of PGN as a determinant of brain inflammation, notably in multiple sclerosis (MS) and its experimental autoimmune encephalomyelitis (EAE) models. Recent studies demonstrate P...
Source: Trends in Molecular Medicine - June 28, 2020 Category: Molecular Biology Authors: Laman JD, 't Hart BA, Power C, Dziarski R Tags: Trends Mol Med Source Type: research

Haptoglobin Therapeutics and Compartmentalization of Cell-Free Hemoglobin Toxicity.
Abstract Hemolysis and accumulation of cell-free hemoglobin (Hb) in the circulation or in confined tissue compartments such as the subarachnoid space is an important driver of disease. Haptoglobin is the Hb binding and clearance protein in human plasma and an efficient antagonist of Hb toxicity resulting from physiological red blood cell turnover. However, endogenous concentrations of haptoglobin are insufficient to provide protection against Hb-driven disease processes in conditions such as sickle cell anemia, sepsis, transfusion reactions, medical-device associated hemolysis, or after a subarachnoid hemorrhage. ...
Source: Trends in Molecular Medicine - June 28, 2020 Category: Molecular Biology Authors: Buehler PW, Humar R, Schaer DJ Tags: Trends Mol Med Source Type: research

Therapeutic Manipulation of mtDNA Heteroplasmy: A Shifting Perspective.
Abstract Mutations of mitochondrial DNA (mtDNA) often underlie mitochondrial disease, one of the most common inherited metabolic disorders. Since the sequencing of the human mitochondrial genome and the discovery of pathogenic mutations in mtDNA more than 30 years ago, a movement towards generating methods for robust manipulation of mtDNA has ensued, although with relatively few advances and some controversy. While developments in the transformation of mammalian mtDNA have stood still for some time, recent demonstrations of programmable nuclease-based technology suggest that clinical manipulation of mtDNA heteropl...
Source: Trends in Molecular Medicine - June 28, 2020 Category: Molecular Biology Authors: Jackson CB, Turnbull DM, Minczuk M, Gammage PA Tags: Trends Mol Med Source Type: research

Genetic and Genomic Mechanisms of Primary Aldosteronism.
Abstract Aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia are the main cause of primary aldosteronism (PA), the most frequent form of secondary hypertension. Mutations in ion channels and ATPases have been identified in APA and inherited forms of PA, highlighting the central role of calcium signaling in PA development. Different somatic mutations are also found in aldosterone-producing cell clusters in adrenal glands from healthy individuals and from patients with unilateral and bilateral PA, suggesting additional pathogenic mechanisms. Recent mouse models have also contributed to a better und...
Source: Trends in Molecular Medicine - June 18, 2020 Category: Molecular Biology Authors: Fernandes-Rosa FL, Boulkroun S, Zennaro MC Tags: Trends Mol Med Source Type: research

TLR2 as a Therapeutic Target in Bacterial Infection.
Abstract Toll-like receptor (TLR) 2 recognizes and responds to threats early in bacterial infections and can influence the downstream immune response to the host's benefit or detriment. Therapeutic modulation of TLR2 signaling represents an underutilized opportunity to moderate the immune response to infection to promote an improved outcome for the host. PMID: 32563557 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - June 17, 2020 Category: Molecular Biology Authors: Simpson ME, Petri WA Tags: Trends Mol Med Source Type: research

First Trial of CRISPR-Edited T cells in Lung Cancer.
Abstract The clinical application of CRISPR-Cas9 gene editing has been eagerly awaited since the first description of the technique in 2013. Lu and colleagues now describe the treatment of 12 patients with nonsmall-cell lung cancer (NSCLC) with PD-1 gene-edited bulk autologous T cells, with results supporting both the feasibility and safety of gene editing in cell therapy. PMID: 32536469 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - June 12, 2020 Category: Molecular Biology Authors: Lacey SF, Fraietta JA Tags: Trends Mol Med Source Type: research

Bacterial Peptidoglycans from Microbiota in Neurodevelopment and Behavior.
Abstract It is increasingly recognized that the gut microbiota profoundly influences many aspects of host development and physiology, including the modulation of brain development and behavior. However, the precise molecular mechanisms and signaling pathways involved in communication between the microbiota and the developing brain remain to be fully elucidated. Germline-encoded pattern-recognition receptors (PRRs) that recognize conserved microbial molecular signatures such as bacterial surface molecules (e.g., peptidoglycans, PGNs) have emerged as potential key regulators of gut microbiota-brain interactions. We ...
Source: Trends in Molecular Medicine - June 4, 2020 Category: Molecular Biology Authors: Gonzalez-Santana A, Diaz Heijtz R Tags: Trends Mol Med Source Type: research

Chondrodysplasias and Aneurysmal Thoracic Aortopathy: An Emerging Tale of Molecular Intersection.
Abstract Although at first glance chondrodysplasia and aneurysmal thoracic aortopathy seem oddly dissimilar, recent lines of evidences indicate that they share molecular similarities. Chondrodysplasias are a group of skeletal disorders characterized by genetic defects in hyaline cartilage. Aneurysmal thoracic aortopathy is the pathological enlargement of the thoracic aorta due to wall weakness, along with its ensuing life-threatening complications (i.e., aortic dissection and/or rupture). Extracellular matrix dysregulation, abnormal TGF-β signaling, and, to a more limited extent, endoplasmic reticulum stress ...
Source: Trends in Molecular Medicine - June 4, 2020 Category: Molecular Biology Authors: Verstraeten A, Meester J, Peeters S, Mortier G, Loeys B Tags: Trends Mol Med Source Type: research

Antibiotic Resistance by Enzymatic Modification of Antibiotic Targets.
Abstract Antibiotic resistance remains a significant threat to modern medicine. Modification of the antibiotic target is a resistance strategy that is increasingly prevalent among pathogens. Examples include resistance to glycopeptide and polymyxin antibiotics that occurs via chemical modification of their molecular targets in the cell envelope. Similarly, many ribosome-targeting antibiotics are impaired by methylation of the rRNA. In these cases, the antibiotic target is subjected to enzymatic modification rather than genetic mutation, and in many instances the resistance enzymes are readily mobilized among patho...
Source: Trends in Molecular Medicine - June 1, 2020 Category: Molecular Biology Authors: Schaenzer AJ, Wright GD Tags: Trends Mol Med Source Type: research

The COVID-19 Pandemic from an Ophthalmologist's Perspective.
Abstract The current coronavirus disease 2019 (COVID-19) pandemic is rapidly spreading around the world. The first doctor to report this new disease was an ophthalmologist: this exemplifies the role of ophthalmologists in an infectious disease pandemic. Here we review how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the eye and discuss implications for ophthalmologists. PMID: 32470381 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - May 31, 2020 Category: Molecular Biology Authors: Bacherini D, Biagini I, Lenzetti C, Virgili G, Rizzo S, Giansanti F Tags: Trends Mol Med Source Type: research

NMDARs in Cell Survival and Death: Implications in Stroke Pathogenesis and Treatment.
Abstract Stroke is a leading cause of death and disability in developed countries. N-methyl-D-aspartate glutamate receptors (NMDARs) have important roles in stroke pathology and recovery. Depending on their subtypes and locations, these NMDARs may promote either neuronal survival or death. Recently, the functions of previously overlooked NMDAR subtypes during stroke were characterized, and NMDARs expressed at different subcellular locations were found to have synergistic rather than opposing functions. Moreover, the complexity of the neuronal survival and death signaling pathways following NMDAR activation was fur...
Source: Trends in Molecular Medicine - May 31, 2020 Category: Molecular Biology Authors: Ge Y, Chen W, Axerio-Cilies P, Wang YT Tags: Trends Mol Med Source Type: research

Development of Humanized Ossicles: Bridging the Hematopoietic Gap.
Abstract Ectopic 'humanized ossicles' (hOss) are miniaturized, engineered human bone organs in mice displaying a similar structure and function to native mouse bones. However, they are composed of human mesenchymal derived cells forming a humanized bone marrow niche. This in vivo reconstitution of human skeletal and hematopoietic compartments provides an opportunity to investigate the cellular and molecular processes involved in their establishment and functions in a human setting. However, current hOs strategies vary in their engineering methods and their downstream applications, undermining comprehensive exploit...
Source: Trends in Molecular Medicine - May 31, 2020 Category: Molecular Biology Authors: Dupard SJ, Grigoryan A, Farhat S, Coutu DL, Bourgine PE Tags: Trends Mol Med Source Type: research

Assessing Toxicity with Human Cell-Based In Vitro Methods.
Abstract In toxicology, there is a strong push towards replacing animal experiments with alternative methods, which include cell-based in vitro methods for the assessment of adverse health effects in humans. High-throughput methods are of central interest due to the large and steadily growing numbers of compounds that require assessment. Tremendous progress has been made during the last decade in developing and applying such methods. Innovative technologies for addressing complex biological interactions include induced pluripotent stem cell- and organoid-based approaches, organotypic coculture systems, and microfl...
Source: Trends in Molecular Medicine - May 31, 2020 Category: Molecular Biology Authors: Zink D, Chuah JKC, Ying JY Tags: Trends Mol Med Source Type: research

Noncoding RNAs versus Protein Biomarkers in Cardiovascular Disease.
Abstract The development of more sensitive protein biomarker assays results in continuous improvements in detectability, extending the range of clinical applications to the detection of subclinical cardiovascular disease (CVD). However, these efforts have not yet led to improvements in risk assessment compared with existing risk scores. Noncoding RNAs (ncRNAs) have been assessed as biomarkers, and miRNAs have attracted most attention. More recently, other ncRNA classes have been identified, including long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs). Here, we compare emerging ncRNA biomarkers in the cardi...
Source: Trends in Molecular Medicine - May 31, 2020 Category: Molecular Biology Authors: Schulte C, Barwari T, Joshi A, Zeller T, Mayr M Tags: Trends Mol Med Source Type: research

Type 2 Diabetes Mellitus Drugs for Alzheimer's Disease: Current Evidence and Therapeutic Opportunities.
Abstract Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) represent two major health burdens with steadily increasing prevalence and accumulating evidence indicates a close relationship between the two disorders. In view of their similar pathogenesis, the potential of T2DM drugs for the treatment of AD has attracted considerable attention in recent years, with inspiring outcomes. Here, we provide a comprehensive overview of the effects of a total of 14 individual drugs (among which are seven T2DM drug types) against AD. Further, we discuss the potential action mechanisms of these T2DM drugs against AD....
Source: Trends in Molecular Medicine - May 31, 2020 Category: Molecular Biology Authors: Meng L, Li XY, Shen L, Ji HF Tags: Trends Mol Med Source Type: research

Harnessing Therapeutic IgE Antibodies to Re-educate Macrophages against Cancer.
Abstract Currently, IgG is the only class of antibodies employed for cancer therapy. However, harnessing the unique biological properties of a different class ( e.g., IgE) could engender potent effector cell activation, and unleash previously untapped immune mechanisms against cancer. IgE antibodies are best known for pathogenic roles in allergic diseases and for protective effector functions against parasitic infestation, often mediated by IgE Fc receptor-expressing macrophages. Notably, IgE possess a very high affinity for cognate Fc receptors expressed by tumor-associated macrophages (TAMs). This paper reviews ...
Source: Trends in Molecular Medicine - May 31, 2020 Category: Molecular Biology Authors: Pellizzari G, Bax HJ, Josephs DH, Gotovina J, Jensen-Jarolim E, Spicer JF, Karagiannis SN Tags: Trends Mol Med Source Type: research

G-quadruplex, Friend or Foe: The Role of the G-quartet in Anticancer Strategies.
Abstract The clinical applicability of G-quadruplexes (G4s) as anticancer drugs is currently being evaluated. Several G4 ligands and aptamers are undergoing clinical trials following the notable examples of quarfloxin and AS1411, respectively. In this review, we summarize the latest achievements and breakthroughs in the use of G4 nucleic acids as both therapeutic tools ('friends', as healing anticancer drugs) and targets ('foes', within the harmful cancer cell), particularly using aptamers and quadruplex-targeted ligands, respectively. We explore the recent research on synthetic G4 ligands toward the discovery of ...
Source: Trends in Molecular Medicine - May 25, 2020 Category: Molecular Biology Authors: Carvalho J, Mergny JL, Salgado GF, Queiroz JA, Cruz C Tags: Trends Mol Med Source Type: research

Promises and Limitations of Neural Stem Cell Therapies for Progressive Multiple Sclerosis.
Abstract Multiple disease-modifying medications with regulatory approval to treat multiple sclerosis (MS) are unable to prevent inflammatory tissue damage in the central nervous system (CNS), and none directly promote repair. Thus, there is an unmet clinical need for therapies that can arrest and reverse the persistent accumulation of disabilities associated with progressive forms of MS (P-MS). Preclinical research has revealed an unexpected ability of neural stem cell (NSC) therapies to provide neurotrophic support and inhibit detrimental host immune responses in vivo following transplantation into the chronicall...
Source: Trends in Molecular Medicine - May 21, 2020 Category: Molecular Biology Authors: Pluchino S, Smith JA, Peruzzotti-Jametti L Tags: Trends Mol Med Source Type: research

Multitissue Multiomics Systems Biology to Dissect Complex Diseases.
Abstract Most complex diseases involve genetic and environmental risk factors, engage multiple cells and tissues, and follow a polygenic or omnigenic model depicting numerous genes contributing to pathophysiology. These multidimensional complexities pose challenges to traditional approaches that examine individual factors. In turn, multitissue multiomics systems biology has emerged to comprehensively elucidate within- and cross-tissue molecular networks underlying gene-by-environment interactions and contributing to complex diseases. The power of systems biology in retrieving novel insights and formulating new hyp...
Source: Trends in Molecular Medicine - May 18, 2020 Category: Molecular Biology Authors: Yang X Tags: Trends Mol Med Source Type: research

Emerging Targets for Cardiovascular Disease Prevention in Diabetes.
Abstract Type 1 and type 2 diabetes mellitus (T1DM and T2DM) increase the risk of atherosclerotic cardiovascular disease (CVD), resulting in acute cardiovascular events, such as heart attack and stroke. Recent clinical trials point toward new treatment and prevention strategies for cardiovascular complications of T2DM. New antidiabetic agents show unexpected cardioprotective benefits. Moreover, genetic and reverse translational strategies have revealed potential novel targets for CVD prevention in diabetes, including inhibition of apolipoprotein C3 (APOC3). Modeling and pharmacology-based approaches to improve ins...
Source: Trends in Molecular Medicine - May 15, 2020 Category: Molecular Biology Authors: Stitziel NO, Kanter JE, Bornfeldt KE Tags: Trends Mol Med Source Type: research

Adult Hippocampal Neurogenesis in Major Depressive Disorder and Alzheimer's Disease.
Abstract Depression and dementia are major public health problems. Major depressive disorder (MDD) and Alzheimer's disease (AD) reciprocally elevate the risk for one another. No effective drug is available to treat AD and about one-third of depressive patients show treatment resistance. The biological connection between MDD and AD is still unclear. Uncovering this link might open novel ways of treatment and prevention to improve patient healthcare. Here, we discuss recent studies specifically on the role of human adult hippocampal neurogenesis (AHN) in MDD and AD. We compare diverse approaches to analyse the effec...
Source: Trends in Molecular Medicine - May 14, 2020 Category: Molecular Biology Authors: Berger T, Lee H, Young AH, Aarsland D, Thuret S Tags: Trends Mol Med Source Type: research

The Gut Microbiota: Emerging Evidence in Autoimmune Diseases.
Abstract The pathogenesis of autoimmune diseases (AIDs) is not only attributed to genetic susceptibilities but also environmental factors, among which, disturbed gut microbiota has attracted increasing attention. Compositional and functional changes of gut microbiota have been reported in various AIDs, and increasing evidence suggests that disturbed gut microbiota contributes to their immunopathogenesis. The accepted mechanisms include abnormal microbial translocation, molecular mimicry, and dysregulation of both local and systemic immunity. Studies have also suggested microbiota-based classification models and th...
Source: Trends in Molecular Medicine - May 10, 2020 Category: Molecular Biology Authors: Zhang X, Chen BD, Zhao LD, Li H Tags: Trends Mol Med Source Type: research

Metabolic Pathways That Control Skin Homeostasis and Inflammation.
rid F Abstract Keratinocytes and skin immune cells are actively metabolizing nutrients present in their microenvironment. This is particularly important in common chronic inflammatory skin diseases such as psoriasis and atopic dermatitis, characterized by hyperproliferation of keratinocytes and expansion of inflammatory cells, thus suggesting increased cell nutritional requirements. Proliferating inflammatory cells and keratinocytes express high levels of glucose transporter (GLUT)1, l-type amino acid transporter (LAT)1, and cationic amino acid transporters (CATs). Main metabolic regulators such as hypoxia-inducib...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Cibrian D, de la Fuente H, Sánchez-Madrid F Tags: Trends Mol Med Source Type: research

Mouth-Watering Results: Clinical Need, Current Approaches, and Future Directions for Salivary Gland Regeneration.
Abstract Permanent damage to the salivary glands and resulting hyposalivation and xerostomia have a substantial impact on patient health, quality of life, and healthcare costs. Currently, patients rely on lifelong treatments that alleviate the symptoms, but no long-term restorative solutions exist. Recent advances in adult stem cell enrichment and transplantation, bioengineering, and gene transfer have proved successful in rescuing salivary gland function in a number of animal models that reflect human diseases and that result in hyposalivation and xerostomia. By overcoming the limitations of stem cell transplants...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Rocchi C, Emmerson E Tags: Trends Mol Med Source Type: research

Cell-to-Cell Transmission of Tau and α-Synuclein.
Cell-to-Cell Transmission of Tau and α-Synuclein. Trends Mol Med. 2020 May 01;: Authors: Uemura N, Uemura MT, Luk KC, Lee VM, Trojanowski JQ Abstract The stereotypical spread of pathological protein inclusions and clinicopathological heterogeneity are well described in neurodegenerative diseases. Accumulating evidence suggests that the former can be attributed to consecutive cell-to-cell transmission of pathological proteins between anatomically connected brain regions, while the latter has been hypothesized to result from the spread of conformationally distinct pathological protein aggregates, ...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Uemura N, Uemura MT, Luk KC, Lee VM, Trojanowski JQ Tags: Trends Mol Med Source Type: research

Microbiome Metabolite Mimics Accelerate Drug Discovery.
Abstract A recent study by Dvořák et al. supports metabolite mimicry as a drug development strategy. A potent agonist of the human pregnane X receptor (hPXR) was designed from two ligands that are products of the microbial catabolism of tryptophan. Its validity was demonstrated in cellular assays and a murine colitis model expressing hPXR by a significant reduction in inflammation biomarkers. PMID: 32359474 [PubMed - in process] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Nuzzo A, Brown JR Tags: Trends Mol Med Source Type: research

FABP4: A New Player in Obesity-Associated Breast Cancer.
Abstract Obesity is known to increase breast cancer incidence and mortality, but the underlying mechanisms remain unsolved. Recent studies demonstrate that adipose fatty acid binding protein (FABP4) promotes obesity-associated breast cancer development, thus suggesting FABP4 as a novel player linking obesity and breast cancer risk. PMID: 32359475 [PubMed - in process] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Zeng J, Sauter ER, Li B Tags: Trends Mol Med Source Type: research

Hair(y) Matters in Melanoma Biology.
Abstract Melanocyte stem cells (MeSCs), one candidate for the cellular origin of melanoma, reside in the bulge region of the hair follicle (HF), an immune-privileged tissue niche with impaired tumor immunosurveillance. Surprisingly, however, primary melanoma is only very rarely associated with HFs. Here, we explore the hypothesis that this profoundly immunoinhibitory signaling environment deprives both MeSCs and melanocytes of the anagen hair matrix of proinflammatory signals required for full oncogenic transformation. Understanding the cellular and molecular mechanisms for generating a putative antimelanoma tissu...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Bedogni B, Paus R Tags: Trends Mol Med Source Type: research

Activity-Based Diagnostics: An Emerging Paradigm for Disease Detection and Monitoring.
Abstract Diagnostics to accurately detect disease and monitor therapeutic response are essential for effective clinical management. Bioengineering, chemical biology, molecular biology, and computer science tools are converging to guide the design of diagnostics that leverage enzymatic activity to measure or produce biomarkers of disease. We review recent advances in the development of these 'activity-based diagnostics' (ABDx) and their application in infectious and noncommunicable diseases. We highlight efforts towards both molecular probes that respond to disease-specific catalytic activity to produce a diagnosti...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Soleimany AP, Bhatia SN Tags: Trends Mol Med Source Type: research

NIRF Nanoprobes for Cancer Molecular Imaging: Approaching Clinic.
Abstract Near-IR fluorescence imaging (NIRFI) is a highly promising technique for improving cancer theranostics in the era of precision medicine. Through the combination with cutting-edge bionanotechnologies, the potential of NIRFI can be greatly broadened. A variety of novel NIRF nanoprobes has been developed with ultimate goals of addressing unmet medical needs. Here, we present recent breakthroughs on the fundamental aspects of NIRFI, such as imaging at long wavelengths (1000-1700 nm), and the use of new approaches (X-rays, chemiluminescence, radioluminescence, etc.) for the excitation of novel nanoprobes. With...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Hu Z, Chen WH, Tian J, Cheng Z Tags: Trends Mol Med Source Type: research

COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives.
Abstract The recent outbreak of COVID-19 in Wuhan turned into a public health emergency of international concern. With no antiviral drugs nor vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are significantly less effective. Here, we report the epidemiological and virological characteristics of the COVID-19 outbreak. Originated in bats, 2019-nCoV/ severe acute respiratory syndrome coronavirus (SARS-CoV)-2 likely experienced adaptive evolution in intermediate hosts before transfer to humans at a concentrated source of transmission. Similarities of rece...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Sun J, He WT, Wang L, Lai A, Ji X, Zhai X, Li G, Suchard MA, Tian J, Zhou J, Veit M, Su S Tags: Trends Mol Med Source Type: research

Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection.
Abstract Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of mucosal immunology and microbiology. This excitement is well founded, as demonstrated by 90% relapse-free cure rates in FMT treatment for recurrent Clostridioides difficile infections. Growing evidence suggests that in addition to bacterial factors, the host immune response during C. difficile...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Frisbee AL, Petri WA Tags: Trends Mol Med Source Type: research

Transcription Factor Inhibition: Lessons Learned and Emerging Targets.
Abstract Transcription factors have roles at focal points in signaling pathways, controlling many normal cellular processes, such as cell growth and proliferation, metabolism, apoptosis, immune responses, and differentiation. Their activity is frequently deregulated in disease and targeting this class of proteins is a major focus of interest. However, the structural disorder and lack of binding pockets have made design of small molecules for transcription factors challenging. Here, we review some of the most recent developments for small molecule inhibitors of transcription factors emphasized in James Darnell's vi...
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Chen A, Koehler AN Tags: Trends Mol Med Source Type: research

Cell-Free DNA and Apoptosis: How Dead Cells Inform About the Living.
We describe how improved knowledge about cfDNA biology could be used for novel therapeutic strategies and how this may affect patient management. PMID: 32359482 [PubMed - in process] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - May 1, 2020 Category: Molecular Biology Authors: Heitzer E, Auinger L, Speicher MR Tags: Trends Mol Med Source Type: research

iNPH as a '2-hit' Intracranial Hydrodynamic Derangement Disease.
PMID: 32345531 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - April 25, 2020 Category: Molecular Biology Authors: Gallina P, Porfirio B, Lolli F Tags: Trends Mol Med Source Type: research

A lncRNA Decoy Predicts Sensitivity to Cisplatin.
Abstract In a recent iScience paper by Fan et al., the long noncoding (lnc)RNA CISAL is shown to form a DNA-RNA triplex and to directly regulate BRCA1 transcription, thereby increasing cisplatin sensitivity and serving as a treatment efficacy biomarker. This opens promising avenues of research from both mechanistic and translational perspectives. PMID: 32277928 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - April 1, 2020 Category: Molecular Biology Authors: Boque-Sastre R, Guil S Tags: Trends Mol Med Source Type: research

Tumor Progression of Breast Cancer during Hyperinsulinemic Obesity.
Abstract Factors of metabolic syndrome including hyperinsulinemia and obesity are well known to increase the risk of cancer incidence and progression. In a recent iScience article, Ramos et al. demonstrate a novel tumor-suppressor role of the circadian transcription factor BMAL1 in triple-negative breast cancer (TNBC) specifically under conditions of hyperinsulinemia. PMID: 32277929 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - April 1, 2020 Category: Molecular Biology Authors: Boese AC, Kang S Tags: Trends Mol Med Source Type: research

Vaccination against Allergy: A Paradigm Shift?
Abstract Since the discovery that IgE antibodies mediate allergy, decades of research have unraveled complex mechanisms associated with conventional immunotherapy and the vital protagonists that shape 'immune tolerance' to allergens. Debate exists on what should constitute the dominant effector mechanism in driving rational drug designs for next-generation immunotherapies. As vaccine technology continues to advance, the development of novel vaccines in this area of continued medical need might stand on a threshold of breakthrough inspired by experiments by Dunbar on the passive vaccination of allergic animals more...
Source: Trends in Molecular Medicine - April 1, 2020 Category: Molecular Biology Authors: Bachmann MF, Mohsen MO, Kramer MF, Heath MD Tags: Trends Mol Med Source Type: research

Heart Failure and Adipose Mesenchymal Stem Cells.
Abstract Mesenchymal stem cells (MSCs) are considered a promising cell type for the treatment of heart failure (HF). In particular, MSCs in adipose tissue are being evaluated as an effective therapeutic tool. However, adipose MSCs are a major source of adipocyte generation and linked to obesity, which is an independent risk factor for HF. MSCs express all of the components of the renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of HF. The local RAS also regulates MSC adipogenesis, indicating a connection between MSC-adipogenesis-obesity and HF. This review examines evidence of the ...
Source: Trends in Molecular Medicine - April 1, 2020 Category: Molecular Biology Authors: Matsushita K Tags: Trends Mol Med Source Type: research

The Centrosome Linker and Its Role in Cancer and Genetic Disorders.
Abstract Centrosome cohesion, the joining of the two centrosomes of a cell, is increasingly appreciated as a major regulator of cell functions such as Golgi organization and cilia positioning. One major element of centrosome cohesion is the centrosome linker that consists of a growing number of proteins. The timely disassembly of the centrosome linker enables centrosomes to separate and assemble a functional bipolar mitotic spindle that is crucial for maintaining genomic integrity. Exciting new findings link centrosome linker defects to cell transformation and genetic disorders. We review recent data on the molecu...
Source: Trends in Molecular Medicine - April 1, 2020 Category: Molecular Biology Authors: Remo A, Li X, Schiebel E, Pancione M Tags: Trends Mol Med Source Type: research

Targeted Avenues for Cancer Treatment: The MEK5-ERK5 Signaling Pathway.
Abstract Twenty years have passed since extracellular signal-regulated kinase 5 (ERK5) and its upstream activator, mitogen-activated protein kinase 5 (MEK5), first emerged onto the cancer research scene. Although we have come a long way in defining the liaison between dysregulated MEK5-ERK5 signaling and the pathogenesis of epithelial and nonepithelial malignancies, selective targeting of this unique pathway remains elusive. Here, we provide an updated review of the existing evidence for a correlation between aberrant MEK5-ERK5 (phospho)proteomic/transcriptomic profiles, aggressive cancer states, and poor patient ...
Source: Trends in Molecular Medicine - April 1, 2020 Category: Molecular Biology Authors: Pereira DM, Rodrigues CMP Tags: Trends Mol Med Source Type: research

Chemical Chaperones as Novel Drugs for Parkinson's Disease.
ve;s I, Ventura S Abstract Parkinson's disease (PD) is characterized by progressive loss of dopaminergic neurons and the accumulation of deposits of α-synuclein (α-syn) in the brain. The pivotal role of α-syn aggregation in PD makes it an attractive target for potential disease-modifying therapies. However, the disordered nature of the protein, its multistep aggregation mechanism, and the lack of structural information on intermediate species complicate the discovery of modulators of α-syn amyloid deposition. Despite these difficulties, small molecules have been shown to block the misfoldin...
Source: Trends in Molecular Medicine - April 1, 2020 Category: Molecular Biology Authors: Pujols J, Peña-Díaz S, Pallarès I, Ventura S Tags: Trends Mol Med Source Type: research

Noncoding RNAs Controlling Telomere Homeostasis in Senescence and Aging.
Abstract Aging is a universal and time-dependent biological decline associated with progressive deterioration of cells, tissues, and organs. Age-related decay can eventually lead to pathology such as cardiovascular and neurodegenerative diseases, cancer, and diabetes. A prominent molecular process underlying aging is the progressive shortening of telomeres, the structures that protect the ends of chromosomes, eventually triggering cellular senescence. Noncoding (nc)RNAs are emerging as major regulators of telomere length homeostasis. In this review, we describe the impact of ncRNAs on telomere function and discuss...
Source: Trends in Molecular Medicine - April 1, 2020 Category: Molecular Biology Authors: Rossi M, Gorospe M Tags: Trends Mol Med Source Type: research

Only 20-25% Deuteration of Polyunsaturated Fatty Acids Prevents Lipid Peroxidation.
PMID: 32033907 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - February 4, 2020 Category: Molecular Biology Authors: Atwal PS, Midei M, Milner P Tags: Trends Mol Med Source Type: research

Human Narratives in Science: The Power of Storytelling.
Abstract Science is fundamentally about people - the people who do science and the people who are affected by science. However, access to these human stories is limited. We argue that these narratives must be captured and shared publicly as an integral part of the scientific process. PMID: 32005566 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine)
Source: Trends in Molecular Medicine - January 28, 2020 Category: Molecular Biology Authors: Muindi FJ, Ramachandran L, Tsai JW Tags: Trends Mol Med Source Type: research