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Trends in Molecular Medicine

Bronwyn M Gunn, Galit Alter
Induction of pathogen-specific binding antibodies has long been considered a signature of protective immunity following vaccination and infection. The humoral immune response is a complex network of antibodies that target different specificities and drive different functions, collectively acting to limit and clear infection either directly, via pathogen neutralization, or indirectly, via pathogen clearance by the innate immune system. Emerging data suggest that not all antibody responses are equal, and qualitative features of antibodies may be key to defining protective immune profiles...
October 15, 2016: Trends in Molecular Medicine
Brian H Shirts, Colin C Pritchard, Tom Walsh
Every single-nucleotide change compatible with life is present in the human population today. Understanding these rare human variants defines an extraordinary challenge for genetics and medicine. The new clinical practice of sequencing many genes for hereditary cancer risk has illustrated the utility of clinical next-generation sequencing in adults, identifying more medically actionable variants than single-gene testing. However, it has also revealed a linear relationship between the length of DNA evaluated and the number of rare 'variants of uncertain significance' reported...
October 11, 2016: Trends in Molecular Medicine
Li Liu, Kang Li, Xin Fu, Christopher Chung, Kang Zhang
Genomic abnormalities are a leading cause of birth defects and pregnancy complications, including in utero growth retardation and risk of miscarriage. Traditional invasive methods detecting such genomic abnormalities pose a relative risk to mother and unborn fetus. Non-invasive prenatal testing (NIPT) is a method that determines the genomic status of a fetus in utero by analyzing circulating fetal DNA in maternal plasma or serum. This review comes at a time when more and more physicians and hospitals might be using NIPT; there is great potential in extending this technology to other diagnostic applications...
October 7, 2016: Trends in Molecular Medicine
Saak V Ovsepian, Valerie B O'Leary, Vasilis Ntziachristos, J Oliver Dolly
In addition to safeguarding the central nervous system (CNS) from the vast majority of pathogens and toxins, transvascular barriers impose immense challenges to the delivery of beneficial cargo. A few toxins and neurotropic viruses capable of penetrating the brain have proved to be potentially valuable for neuron targeting and enhanced transfer of restorative medicine and therapeutic genes. Here we review molecular concepts and implications of the highly neurotropic tetanus toxin (TeTx) and botulinum neurotoxins (BoNTs) and their ability to infiltrate and migrate throughout neurons...
October 5, 2016: Trends in Molecular Medicine
Shaun P Steele, Stephanie J Melchor, William A Petri
A recent surge of interest in tuft cells, which are chemosensory intestinal epithelial cells, has uncovered new functional roles for these cells in colorectal cancer, metabolic signaling, and type 2 immunity. Here, we explore emerging evidence suggesting that tuft cells are critical for protection during enteric infections and inflammatory responses.
October 4, 2016: Trends in Molecular Medicine
Amy Chang, Ynuk Bossé
Asthma is a lung disorder triggered by various airborne factors in susceptible individuals. Although generally controlled, asthma can be severe and difficult to treat. Presently, increasing numbers of pharmaceuticals capable of blocking or mimicking specific endogenous molecules are undergoing clinical trials in asthmatic individuals whose symptoms are poorly controlled despite adherence to guideline therapies. Unfortunately, only a few, meticulously selected patients have been found to minimally benefit. These findings not only confirm that the molecular pathogenesis of severe asthma is variable between patients but also suggest that each molecular defect is likely to contribute little on its own in each patient...
September 28, 2016: Trends in Molecular Medicine
Lisa K McLellan, David A Hunstad
The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities...
September 27, 2016: Trends in Molecular Medicine
Feixiong Cheng, James L Murray, Donald H Rubin
To date, no antiviral agents have been approved for treating Zika virus (ZIKV) infection. Two recent drug-repurposing studies published in Cell Host & Microbe and Nature Medicine demonstrated that screening FDA-approved drugs for antiviral activity is a promising strategy for identifying therapeutics with novel activity against ZIKV infection.
September 27, 2016: Trends in Molecular Medicine
Manuel A Fernandez-Rojo, Grant A Ramm
Caveolin-1 (CAV1), the structural protein of caveolae in the plasma membrane, has emerged as a regulator of liver function. CAV1 modulates several molecular pathways leading to the regulation of hepatic lipid accumulation, lipid and glucose metabolism, mitochondrial biology, and hepatocyte proliferation. CAV1 thus plays a crucial role in maintaining hepatic physiology during metabolic adaptation to fasting, liver steatosis, and hepatocyte proliferation associated with liver regeneration. With failure of such processes, CAV1 has been implicated in the modulation of cholestasis, hepatitis, cirrhosis, and hepatocarcinogenesis...
October 2016: Trends in Molecular Medicine
Davide Ferrari, Nicoletta Bianchi, Holger K Eltzschig, Roberto Gambari
MicroRNAs (miRNAs) are small non-coding RNA molecules capable of silencing mRNA targets. miRNA dysregulation has been linked to cancer development, cardiovascular and neurological diseases, lipid metabolism, and impaired immunity. Therefore, miRNAs are gaining interest as putative novel disease biomarkers and therapeutic targets. Recent studies have shown that purinergic surface receptors activated by extracellular nucleotides (ATP, ADP, UTP, UDP), and by nucleosides such as adenosine (ADO), are subject to miRNA regulation...
October 2016: Trends in Molecular Medicine
Pamela M Odorizzi, Margaret E Feeney
Pregnancy-associated malaria, including placental malaria, causes significant morbidity and mortality worldwide. Recently, it has been suggested that in utero exposure of the fetus to malaria antigens may negatively impact the developing immune system and result in tolerance to malaria. Here, we review our current knowledge of fetal immunity to malaria, focusing on the dynamic interactions between maternal malaria infection, placental development, and the fetal immune system. A better understanding of the long-term impact of in utero malaria exposure on the development of natural immunity to malaria, immune responses to other childhood pathogens, and vaccine immunogenicity is urgently needed...
October 2016: Trends in Molecular Medicine
Davide D'Amico, Gianluca Canettieri
Developmental Hedgehog (Hh) signaling is found deregulated in a broad spectrum of human malignancies and, thus, is an attractive target for cancer therapy. Currently available Hh inhibitors have shown the rapid occurrence of drug resistance, due to altered signaling in collateral pathways. Emerging observations suggest that Hh signaling regulates protein translation in pathways that depend both on Cap- and IRES-mediated translation. In addition, translational regulators have been shown to modulate Hh function...
October 2016: Trends in Molecular Medicine
Michael A Dyer
Retinoblastoma is a rare childhood cancer of the developing retina, and studies on this orphan disease have led to fundamental discoveries in cancer biology. Retinoblastoma has also emerged as a model for translational research for pediatric solid tumors, which is particularly important as personalized medicine expands in oncology. Research on retinoblastomas has been combined with the exploration of retinal development and retinal degeneration to advance a new model of cell type-specific disease susceptibility termed 'cellular pliancy'...
October 2016: Trends in Molecular Medicine
Ilianna Zoi, Michalis V Karamouzis, Christos Adamopoulos, Athanasios G Papavassiliou
ErbB family members, ErbB1/EGFR/HER-1, ErbB2/HER-2, ErbB3/HER-3 and ErbB4/HER-4, have been implicated in breast cancer (BC) tumorigenicity. Recently, crucial roles for RANK/RANKL signaling in addition to key downstream factor NF-κB have been demonstrated in mammary tumorigenesis. Here, we present the hypothesis of a novel association between ErbB and RANK pathways in promoting BC. The proposed model alludes to the cross-talk that might occur between RANK and ErbB receptors. This interplay might regulate RANK signaling and consequently, modulate carcinogenesis, mainly in ErbB2 over-expressing BC cells...
October 2016: Trends in Molecular Medicine
Krishna S Tummala, Filippos Kottakis, Nabeel Bardeesy
Cancer requires mechanisms to mitigate reactive oxygen species (ROS) generated during rapid growth, such as induction of the antioxidant transcription factor, Nrf2. However, the targets of ROS-mediated cytotoxicity are unclear. Recent studies in pancreatic cancer show that redox control by Nrf2 prevents cysteine oxidation of the mRNA translational machinery, thereby supporting efficient protein synthesis.
October 2016: Trends in Molecular Medicine
Maria Paz Zafra, Lukas E Dow
Generating new mouse models of cancer is a challenging and laborious task that can require years of investment to interrogate a single gene. Now, Jonkers and colleagues describe the first application of CRISPR-based genome editing in the mammary gland, providing a new approach to dissect complex genetic interactions in vivo.
October 2016: Trends in Molecular Medicine
Dmitriy I Podolskiy, Vadim N Gladyshev
Two recent stimulating publications have examined the causes of cancer, comparing 'bad luck' versus environment as main risk factors for cancer incidence. However, bringing aging into the picture might question the entire debate.
October 2016: Trends in Molecular Medicine
Rick L Tarleton
Chagas disease is the highest impact parasitic disease in the Americas, yet remains virtually unknown and untreated, despite the fact that the infection is curable and the global problem of Chagas disease is manageable. The causes of this situation and how it can be changed are the focus of this communication.
October 2016: Trends in Molecular Medicine
Silvia Gazzin, Libor Vitek, Jon Watchko, Steven M Shapiro, Claudio Tiribelli
Unconjugated bilirubin (UCB) is known to be one of the most potent endogenous antioxidant substances. While hyperbilirubinemia has long been recognized as an ominous sign of liver dysfunction, recent data strongly indicate that mildly elevated bilirubin (BLB) levels can be protective against an array of diseases associated with increased oxidative stress. These clinical observations are supported by new discoveries relating to the role of BLB in immunosuppression and inhibition of protein phosphorylation, resulting in the modulation of intracellular signaling pathways in vascular biology and cancer, among others...
September 2016: Trends in Molecular Medicine
Rajendra Raghow
Pathological enlargement of the heart, represented by hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), occurs in response to many genetic and non-genetic factors. The clinical course of cardiac hypertrophy is remarkably variable, ranging from lifelong absence of symptoms to rapidly declining heart function and sudden cardiac death (SCD). Unbiased omics studies have begun to provide a glimpse into the molecular framework underpinning altered mechanotransduction, mitochondrial energetics, oxidative stress, and extracellular matrix in the heart undergoing physiological and pathological hypertrophy...
September 2016: Trends in Molecular Medicine
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