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Trends in Molecular Medicine

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https://www.readbyqxmd.com/read/28089302/germinal-center-lymphocyte-ratios-and-successful-hiv-vaccines
#1
Paula Gonzalez-Figueroa, Jonathan A Roco, Carola G Vinuesa
Current HIV vaccines are poor inducers of neutralizing antibodies (nAbs). A recent study in Cell Reports used serial fine-needle aspirates from rhesus macaque lymph nodes following HIV-1 surface envelope glycoprotein (Env) trimer immunization, generating a substantial production of HIV-1 nAbs. A remarkable correlation was found between antibody titers and a high frequency and ratio of germinal center B and T follicular helper (TFH) lymphocytes.
January 11, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28082126/metabolic-syndrome-one-speckled-stone-kills-a-flock-of-birds
#2
Ylva Bonde, Bo Angelin
Effectively treating metabolic syndrome and its progression to type 2 diabetes, steatohepatitis and cardiovascular disease remain a major clinical challenge. The use of a novel engineered molecule that combines thyroid hormone and glucagon to target liver and adipose tissue might provide a new 'magic bullet' with exciting future prospects.
January 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28041781/the-fountain-of-youth-by-targeting-senescent-cells
#3
REVIEW
Peter L J de Keizer
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner...
December 20, 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28041565/the-fountain-of-youth-by-targeting-senescent-cells
#4
REVIEW
Peter L J de Keizer
The potential to reverse aging has long been a tantalizing thought, but has equally been considered mere utopia. Recently, the spotlights have turned to senescent cells as being a culprit for aging. Can these cells be therapeutically eliminated? When so? And is this even safe? Recent developments in the tool box to study senescence have made it possible to begin addressing these questions. It will be especially relevant to identify how senescence impairs tissue rejuvenation and to prospectively design compounds that can both target senescence and stimulate rejuvenation in a safe manner...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27989642/microrna-regulation-of-rna-virus-replication-and-pathogenesis
#5
REVIEW
Derek W Trobaugh, William B Klimstra
microRNAs (miRNAs) are non-coding RNAs that regulate many processes within a cell by manipulating protein levels through direct binding to mRNA and influencing translation efficiency, or mRNA abundance. Recent evidence demonstrates that miRNAs can also affect RNA virus replication and pathogenesis through direct binding to the RNA virus genome or through virus-mediated changes in the host transcriptome. Here, we review the current knowledge on the interaction between RNA viruses and cellular miRNAs. We also discuss how cell and tissue-specific expression of miRNAs can directly affect viral pathogenesis...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27989641/targeting-vascular-remodeling-to-treat-pulmonary-arterial-hypertension
#6
REVIEW
A A Roger Thompson, Allan Lawrie
Pulmonary arterial hypertension (PAH) describes a group of conditions with a common hemodynamic phenotype of increased pulmonary artery pressure, driven by progressive remodeling of small pulmonary arteries, leading to right heart failure and death. Vascular remodeling is the key pathological feature of PAH, but treatments targeting this process are lacking. In this review, we summarize important advances in our understanding of PAH pathogenesis from novel genetic and epigenetic factors, to cell metabolism and DNA damage...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27988109/receptor-tyrosine-kinases-translocation-partners-in-hematopoietic-disorders
#7
REVIEW
Katelyn N Nelson, Malalage N Peiris, April N Meyer, Asma Siari, Daniel J Donoghue
Receptor tyrosine kinases (RTKs) activate various signaling pathways and regulate cellular proliferation, survival, migration, and angiogenesis. Malignant neoplasms often circumvent or subjugate these pathways by promoting RTK overactivation through mutation or chromosomal translocation. RTK translocations create a fusion protein containing a dimerizing partner fused to an RTK kinase domain, resulting in constitutive kinase domain activation, altered RTK cellular localization, upregulation of downstream signaling, and novel pathway activation...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27986421/bacterial-biofilms-in-colorectal-cancer-initiation-and-progression
#8
REVIEW
Shan Li, Sergey R Konstantinov, Ron Smits, Maikel P Peppelenbosch
Intestinal microbiota have emerged as an important factor in colorectal cancer (CRC) initiation and progression. The currently prominent view on bacterial tumorigenesis is that CRC initiation is triggered by local mucosal colonization with specific pathogens (drivers), and that subsequent changes in the peritumoral environment allow colonization by opportunistic (passenger) microbes, further facilitating disease progression. Screening for CRC 'driver-passenger' microorganisms might thus allow early CRC diagnosis or preventive intervention...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27986420/fumarates-and-cancer
#9
Gwenny M Fuhler, Hester Eppinga, Maikel P Peppelenbosch
Accumulation of intermediate metabolites of the tricarboxylic acid (TCA) cycle in tumor cells can cause epithelial-to-mesenchymal transition (EMT), although the exact mechanisms remain elusive. Recent studies show that the oncometabolite fumarate, which accumulates in fumarate hydratase-deficient renal cancers, confers tumor aggressiveness by causing epigenetic changes in the antimetastatic miRNA cluster mir-200ba429. This may have important implications for the use of fumarates in the clinic.
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27914866/co-signaling-molecules-in-maternal-fetal-immunity
#10
REVIEW
Yuan-Yuan Xu, Song-Cun Wang, Da-Jin Li, Mei-Rong Du
Physiologically, a successful pregnancy requires the maternal immune system to recognize and tolerate the semiallogeneic fetus, and allow for normal invasion of trophoblasts. Thus, pregnancy complications are considered to be associated with dysfunctional maternal-fetal crosstalk. Co-signaling molecules are a group of cell surface molecules that positively or negatively modulate the immune response. Well studied in the fields of oncology and transplantation, they are also suggested to be involved in maternal-fetal crosstalk...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27889424/hiv-vaccines-one-step-closer
#11
Michael Sze Yuan Low, David Tarlinton
Currently there is no effective vaccine against human immunodeficiency virus (HIV). Four recently published studies in Cell and Immunity now show that using planned sequential boosting with antigens to guide the humoral response towards broadly neutralizing antibodies could provide a solution to achieving vaccination against HIV-1.
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27887808/norovirus-regulation-by-host-and-microbe
#12
REVIEW
Megan T Baldridge, Holly Turula, Christiane E Wobus
Norovirus (NoV) infection is the leading cause of epidemic gastroenteritis globally, and can lead to detrimental chronic infection in immunocompromised hosts. Despite its prevalence as a cause of diarrheal illness, the study of human NoVs (HNoVs) has historically been limited by a paucity of models. The use of murine NoV (MNoV) to interrogate mechanisms of host control of viral infection has facilitated the exploration of different genetic mouse models, revealing roles for both innate and adaptive immunity in viral regulation...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27866924/bacterial-pathogens-versus-autophagy-implications-for-therapeutic-interventions
#13
REVIEW
Jacqueline M Kimmey, Christina L Stallings
Research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. In this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. Instead, studies in animal models have revealed that autophagy-associated proteins often function outside of xenophagy to influence bacterial pathogenesis...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27840066/small-rna-modifications-integral-to-function-and-disease
#14
REVIEW
Xudong Zhang, Aaron E Cozen, Ying Liu, Qi Chen, Todd M Lowe
Small RNAs have the potential to store a secondary layer of labile biological information in the form of modified nucleotides. Emerging evidence has shown that small RNAs including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs) and tRNA-derived small RNAs (tsRNAs) harbor a diversity of RNA modifications. These findings highlight the importance of RNA modifications in the modulation of basic properties such as RNA stability and other complex physiological processes involved in stress responses, metabolism, immunity, and epigenetic inheritance of environmentally acquired traits, among others...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27836419/ebv-infection-and-multiple-sclerosis-lessons-from-a-marmoset-model
#15
REVIEW
Bert A 'tHart, Yolanda S Kap, Elena Morandi, Jon D Laman, Bruno Gran
Multiple sclerosis (MS) is thought to be initiated by the interaction of genetic and environmental factors, eliciting an autoimmune attack on the central nervous system. Epstein-Barr virus (EBV) is the strongest infectious risk factor, but an explanation for the paradox between high infection prevalence and low MS incidence remains elusive. We discuss new data using marmosets with experimental autoimmune encephalomyelitis (EAE) - a valid primate model of MS. The findings may help to explain how a common infection can contribute to the pathogenesis of MS...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27825668/siderophores-in-iron-metabolism-from-mechanism-to-therapy-potential
#16
REVIEW
Briana R Wilson, Alexander R Bogdan, Masaki Miyazawa, Kazunori Hashimoto, Yoshiaki Tsuji
Iron is an essential nutrient for life. During infection, a fierce battle of iron acquisition occurs between the host and bacterial pathogens. Bacteria acquire iron by secreting siderophores, small ferric iron-binding molecules. In response, host immune cells secrete lipocalin 2 (also known as siderocalin), a siderophore-binding protein, to prevent bacterial reuptake of iron-loaded siderophores. To counter this threat, some bacteria can produce lipocalin 2-resistant siderophores. This review discusses the recently described molecular mechanisms of siderophore iron trafficking between host and bacteria, highlighting the therapeutic potential of exploiting pathogen siderophore machinery for the treatment of antibiotic-resistant bacterial infections...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27825667/cell-intrinsic-barriers-of-t-cell-based-immunotherapy
#17
REVIEW
Hazem E Ghoneim, Anthony E Zamora, Paul G Thomas, Ben A Youngblood
Prolonged exposure of CD8(+) T cells to their cognate antigen can result in exhaustion of effector functions enabling the persistence of infected or transformed cells. Recent advances in strategies to rejuvenate host effector function using Immune Checkpoint Blockade have resulted in tremendous success towards the treatment of several cancers. However, it is unclear if T cell rejuvenation results in long-lived antitumor functions. Emerging evidence suggests that T cell exhaustion may also represent a significant impediment in sustaining long-lived antitumor activity by chimeric antigen receptor T cells...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27793600/is-it-time-to-fold-the-cysts-away
#18
Matteus Krappitz, Anna-Rachel Gallagher, Sorin Fedeles
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2, encoding polycystin-1 and polycystin-2, respectively. Optimizing the folding environment for polycystin-1 missense mutations may have a critical effect on the progression of ADPKD in animal models and could potentially lead to tangible therapeutic options for subgroups of ADPKD patients.
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27793599/a-disease-or-not-a-disease-aging-as-a-pathology
#19
Timothy V Gladyshev, Vadim N Gladyshev
The debate on the relationship between aging and disease is centered on whether aging is a normal/natural/physiological process or it represents a pathology. Considering this relationship from medical, molecular, social, and historical perspectives, we argue that aging is neither a disease, nor a non-disease. Instead, it combines all age-related diseases and their preclinical forms, in addition to other pathological changes.
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27756530/modulating-antibody-functionality-in-infectious-disease-and-vaccination
#20
REVIEW
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...
November 2016: Trends in Molecular Medicine
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