Abstract：
:Inherited bone marrow failure syndromes (IBMFS) are a group of cancer-prone genetic diseases characterized by hypocellular bone marrow with impairment in one or more hematopoietic lineages. The pathogenesis of IBMFS involves mutations in several genes which encode for proteins involved in DNA repair, telomere biology and ribosome biogenesis. The classical IBMFS include Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), Fanconi anemia (FA), dyskeratosis congenita (DC), and severe congenital neutropenia (SCN). IBMFS are associated with high risk of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and solid tumors. Unfortunately, no specific pharmacological therapies have been highly effective for IBMFS. Hematopoietic stem cell transplantation provides a cure for aplastic or myeloid neoplastic complications. However, it does not affect the risk of solid tumors. Since approximately 28% of FA, 24% of SCN, 21% of DBA, 20% of SDS, and 17% of DC patients harbor nonsense mutations in the respective IBMFS-related genes, we discuss the use of the nonsense suppression therapy in these diseases. We recently described the beneficial effect of ataluren, a nonsense suppressor drug, in SDS bone marrow hematopoietic cells ex vivo. A similar approach could be therefore designed for treating other IBMFS. In this review we explain in detail the new generation of nonsense suppressor molecules and their mechanistic roles. Furthermore, we will discuss strengths and limitations of these molecules which are emerging from preclinical and clinical studies. Finally we discuss the state-of-the-art of preclinical and clinical therapeutic studies carried out for IBMFS.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Bezzerri V,Api M,Allegri M,Fabrizzi B,Corey SJ,Cipolli Mdoi
10.3390/ijms21134672subject
Has Abstractpub_date
2020-06-30 00:00:00issue
13issn
1422-0067pii
ijms21134672journal_volume
21pub_type
杂志文章,评审abstract：:Neuropeptides such as vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) are present in nerve fibers of bone tissues and have been suggested to potentially regulate bone remodeling. Oscillatory fluid flow (OFF)-induced shear stress is a potent signal in mechanotransduction that is capable o...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms15045874
更新日期：2014-04-08 00:00:00
abstract：:The members of the Burkholderia genus are characterized by high versatility and adaptability to various ecological niches. With the availability of the genome sequences of numerous species of Burkholderia, many studies have been conducted to elucidate the unique features of this exceptional group of bacteria. Genomic ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20010121
更新日期：2018-12-29 00:00:00
abstract：:Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have been well described, r...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21238885
更新日期：2020-11-24 00:00:00
abstract：:Genome stability requires tight regulation of DNA replication to ensure that the entire genome of the cell is duplicated once and only once per cell cycle. In mammalian cells, origin activation is controlled in space and time by a cell-specific and robust program called replication timing. About 100,000 potential repl...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19113569
更新日期：2018-11-12 00:00:00
abstract：:Acute rejection (AR) of a kidney graft in renal transplant recipients is associated with microvascular injury in graft dysfunction and, ultimately, graft failure. Circulating long noncoding RNAs (lncRNAs) may be suitable markers for vascular injury in the context of AR. Here, we first investigated the effect of AR aft...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21165616
更新日期：2020-08-05 00:00:00
abstract：:MicroRNAs (miRNAs) play an essential role in the regulation of almost all the biological processes, including melanogenesis. MiR-27a-3p is nearly six times higher in white alpaca skin compared to brown skin, which indicates that miR-27a-3p may be a candidate regulator for melanogenesis. Wnt3a plays an important role i...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms160510921
更新日期：2015-05-14 00:00:00
abstract：:Hepatocyte growth factor (HGF) is an endogenously expressed bioactive substance that has a strong anti-apoptotic effect. In this study, we biochemically and histologically characterized the effects of rh-HGF on in vitro human hepatocyte injury and mouse acute liver failure (ALF) models, both of which were induced by a...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20081821
更新日期：2019-04-12 00:00:00
abstract：:Biomarkers for the early detection of pancreatic cancer are urgently needed. The aim of this pilot study was to evaluate changes in serum N-glycoproteins and their glycosylation status prior to clinical presentation of pancreatic cancer that may be potential biomarkers. Prediagnosis serum samples pooled according to f...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18122670
更新日期：2017-12-09 00:00:00
abstract：:Mechanical unloading simultaneously induces muscle and bone loss, but its mechanisms are not fully understood. The interactions between skeletal muscle and bone have been recently noted. Although canonical wingless-related integration site (Wnt)/β-catenin signaling is crucial for bone metabolism, its roles in the musc...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21072547
更新日期：2020-04-06 00:00:00
abstract：:Mango is affected by different decline disorders causing significant losses to mango growers. In the United Arab Emirates (UAE), the pathogen was isolated from all tissues sampled from diseased trees affected by Lasiodiplodia theobromae. Symptoms at early stages of the disease included general wilting appearance of ma...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18102086
更新日期：2017-10-20 00:00:00
abstract：:Phosphate (Pi) is a pivotal nutrient that constraints plant development and productivity in natural ecosystems. Land colonization by plants, more than 470 million years ago, evolved adaptive mechanisms to conquer Pi-scarce environments. However, little is known about the molecular basis underlying such adaptations at ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21218354
更新日期：2020-11-07 00:00:00
abstract：:Heat stress (HS) is an important factor for the survival of the marine organism Apostichopus japonicus. Lysine acetylation is a pivotal post-translational modification that modulates diverse physiological processes including heat shock response (HSR). In this study, 4028 lysine acetylation sites in 1439 proteins were ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20184423
更新日期：2019-09-09 00:00:00
abstract：:NF-E2-related factor 2 (Nrf2) has been identified as a master regulatory factor in the protection of cells from oxidative and electrophilic stress. However, overexpression of Nrf2 in lung cancer may cause chemoresistance, as well as radioresistance. In this study, we examined the relationship between radioresistance a...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17070997
更新日期：2016-06-24 00:00:00
abstract：:Preterm birth (PTB) can be defined as the endpoint of a complex process that could be influenced by maternal and environmental factors. Epigenetics recently emerged as an interesting field of investigation since it represents an important mechanism of regulation. This study evaluates epigenetic impact of preterm birth...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21145044
更新日期：2020-07-17 00:00:00
abstract：:Nicotine causes tobacco dependence, which may result in fatal respiratory diseases. The striatum is a key structure of forebrain basal nuclei associated with nicotine dependence. In the striatum, glutamate release is increased when α7 nicotinic acetylcholine receptors expressed in the glutamatergic terminals are expos...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20122943
更新日期：2019-06-16 00:00:00
abstract：:Unlike orthodox species, seed recalcitrance is poorly understood, especially at the molecular level. In this regard, seed maturation and germination were studied in the non-orthodox Quercus ilex by using a proteomics strategy based on two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption ioni...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21144870
更新日期：2020-07-09 00:00:00
abstract：:It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn't been elucidated. This study was therefore conducted to assess the association between M2 and peritoneal fi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms140510369
更新日期：2013-05-17 00:00:00
abstract：:Aphids are phloem feeders that cause large damage globally as pest insects. They induce a variety of responses in the host plant, but not much is known about which responses are promoting or inhibiting aphid performance. Here, we investigated whether one of the responses induced in barley by the cereal aphid, bird che...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18061317
更新日期：2017-06-20 00:00:00
abstract：:Chestnut (Castanea mollissima) is a deciduous tree species with major economic and ecological value that is widely used in the study of floral development in woody plants due its monoecious and out-of-proportion characteristics. Squamosa promoter-binding protein-like (SPL) is a plant-specific transcription factor that...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20071577
更新日期：2019-03-29 00:00:00
abstract：:Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase, which is the key ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21093144
更新日期：2020-04-29 00:00:00
abstract：:Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N¹-acetyl-N¹-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18051014
更新日期：2017-05-08 00:00:00
abstract：BACKGROUND:Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cel...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18040852
更新日期：2017-04-17 00:00:00
abstract：:Eukaryotic cells express a large variety of RNA binding proteins (RBPs), with diverse affinities and specificities towards target RNAs. These proteins play a crucial role in almost every aspect of RNA biogenesis, expression and function. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a complex and diverse f...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms140918999
更新日期：2013-09-16 00:00:00
abstract：:Up to 30-50% of patients with locally advanced prostate cancer (PCa) undergoing radiotherapy (RT) experience biochemical recurrence (BCR). The immune system affects the RT response. Immunogenetics could define new biomarkers for personalization of PCa patients' treatment. The aim of this study is to define the immunog...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20092082
更新日期：2019-04-27 00:00:00
abstract：:CZ48, chemically camptothecin-20-O-propionate hydrate, is currently under clinical investigation. The kinetics of the metabolite camptothecin (CPT) formation and of CZ48 depletion in mouse and human liver microsomes in the presence or absence of NADPH was examined. The formation rate of camptothecin in human liver mic...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms13055498
更新日期：2012-01-01 00:00:00
abstract：:Obesity is a multifactorial disease that can lead to other health issues. Glucagon-like peptide-1(GLP-1), as one of the satiety signal, has been linked with appetite suppression and weight loss. Due to the limitations of GLP-1 and its analogues, alternative treatments such as herbal therapies have become popular. The ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21082854
更新日期：2020-04-19 00:00:00
abstract：:The d-galactose (d-gal)-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, k...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17010098
更新日期：2016-01-13 00:00:00
abstract：:Recent evidence suggests that autophagy impairment is implicated in the epileptogenic mechanisms downstream of mTOR hyperactivation. This holds true for a variety of genetic and acquired epileptic syndromes besides malformations of cortical development which are classically known as mTORopathies. Autophagy suppression...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21051642
更新日期：2020-02-28 00:00:00
abstract：:The emergence of multidrug-resistant bacteria is a major global health concern. The search for new therapies has brought bacteriophages into the spotlight, and new phages are being described as possible therapeutic agents. Among the bacteria that are most extensively resistant to current antibiotics is Klebsiella pneu...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21093160
更新日期：2020-04-30 00:00:00
abstract：:Triple negative breast cancer (TNBC) is a difficult to treat disease due to the absence of the three unique receptors estrogen, progesterone and herceptin-2 (HER-2). To improve the current therapy and overcome the resistance of TNBC, there is unmet need to develop an effective targeted therapy. In this regard, one of ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19030838
更新日期：2018-03-13 00:00:00
