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Molecular Genetics and Metabolism Mar 2019Heterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern;...
BACKGROUND
Heterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern; it is therefore important to examine outcomes of enzyme replacement therapy (ERT) in the female patient population specifically. This paper presents the findings of a systematic literature review of treatment outcomes with ERT in adult female patients.
METHODS
A comprehensive systematic literature review was conducted through January 2017 to retrieve published papers with original data on ERT in the treatment of Fabry disease. The review included all original articles that presented ERT outcomes data on patients with Fabry disease, irrespective of the study type.
RESULTS
Clinical evidence for the efficacy of ERT in female patients was available from 67 publications including six clinical trial publications, and indicates significant reductions in plasma and urine globotriaosylceramide (GL-3) accumulation (in female patients with elevated pre-treatment levels) and improvements in cardiac parameters and quality of life (QoL). To date, data are insufficient to conclude on the effects of ERT on the nervous system, gastrointestinal manifestations, and pain in female patients with Fabry disease.
CONCLUSIONS
This review of available literature data demonstrates that ERT in adult female patients with Fabry disease has a beneficial effect on GL-3 levels and cardiac outcomes. The current evidence also suggests that ERT may improve QoL in this patient population, though further studies are needed to examine these results.
Topics: Clinical Trials as Topic; Enzyme Replacement Therapy; Fabry Disease; Female; Gastrointestinal Tract; Humans; Isoenzymes; Nervous System; Observational Studies as Topic; Pain; Quality of Life; Recombinant Proteins; Treatment Outcome; Trihexosylceramides; alpha-Galactosidase
PubMed: 30413388
DOI: 10.1016/j.ymgme.2018.09.007 -
Biochimica Et Biophysica Acta.... Jul 2019The endolysosomal, non-selective cation channels, two-pore channels (TPCs) and mucolipins (TRPMLs), regulate intracellular membrane dynamics and autophagy. While... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The endolysosomal, non-selective cation channels, two-pore channels (TPCs) and mucolipins (TRPMLs), regulate intracellular membrane dynamics and autophagy. While partially compensatory for each other, isoform-specific intracellular distribution, cell-type expression patterns, and regulatory mechanisms suggest different channel isoforms confer distinct properties to the cell.
SCOPE OF REVIEW
Briefly, established TPC/TRPML functions and interaction partners ('interactomes') are discussed. Novel TRPML3 interactors are shown, and a meta-analysis of experimentally obtained channel interactomes conducted. Accordingly, interactomes are compared and contrasted, and subsequently described in detail for TPC1, TPC2, TRPML1, and TRPML3.
MAJOR CONCLUSIONS
TPC interactomes are well-defined, encompassing intracellular membrane organisation proteins. TRPML interactomes are varied, encompassing cardiac contractility- and chaperone-mediated autophagy proteins, alongside regulators of intercellular signalling.
GENERAL SIGNIFICANCE
Comprising recently proposed targets to treat cancers, infections, metabolic disease and neurodegeneration, the advancement of TPC/TRPML understanding is of considerable importance. This review proposes novel directions elucidating TPC/TRPML relevance in health and disease. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
Topics: Animals; Calcium Channels; Calcium Signaling; Humans; Transient Receptor Potential Channels
PubMed: 30395881
DOI: 10.1016/j.bbamcr.2018.10.020 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2018This study aimed to review trans lational studies focusing on third molar removal surgeries through a systematic analytical approach.
Preemptive analgesia-related gene and protein expression in third molar surgeries under non steroidal anti-inflammatory drug protocols: A PROSPERO-registered systematic review of clinical studies.
BACKGROUND
This study aimed to review trans lational studies focusing on third molar removal surgeries through a systematic analytical approach.
MATERIAL AND METHODS
A PROSPERO-registered systematic review (CRD42017060455) was conducted following the PRISMA statement to summarize current knowledge on gene expression in third molar surgeries. A search was performed in PubMed's Medline and Scopus databases, without date or language restrictions, using the logical expression {[(Third molar) OR (preemptive) OR (cyclooxygenase inhibitors) OR (acute inflammation) AND (gene expression)]}.
RESULTS
All studies included in the analysis evaluated gene expression in a third molar extraction model, using the preemptive analgesia methodology in seven investigations. The sample analyzed was obtained from gingival tissue biopsy (n=4), blood (n=1), transudate (n=1) and gingival tissue biopsy/transudate (n=1). There were differences with respect to evaluated genes, drug protocol, sample studied, and method for evaluating gene expression.
CONCLUSIONS
Third molar surgeries were found to be associated with different COX-related gene expression patterns. Although inflammatory events following the surgical procedure are associated with COX isoforms, data from preemptive analgesia studies are scarce, especially from studies correlating gene expression and clinical parameters. In the future, from a clinical perspective, identifying the molecular targets of a drug based on individual gene expression may be helpful to delineate specific third molar, surgery-related, preemptive analgesia protocols.
Topics: Analgesia; Anti-Inflammatory Agents, Non-Steroidal; Gene Expression; Humans; Molar, Third; Prostaglandin-Endoperoxide Synthases; Protein Biosynthesis
PubMed: 30341263
DOI: 10.4317/medoral.22576 -
American Journal of Reproductive... Dec 2018Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is...
Oxidative stress (OS) plays a role in uterine tissue remodeling during pregnancy and parturition. While p38 MAPK is an OS-response kinase, a precise functional role is unknown. Therefore, we conducted a systematic review of literature on p38 MAPK expression, activation, and function in reproductive tissues throughout pregnancy and parturition, published between January 1980 and August 2017, using four electronic databases (Web of Science, PubMed, Medline, and CoCHRANE). We identified 418 reports; 108 were selected for full-text evaluation and 74 were included in final review. p38 MAPK was investigated using feto-maternal primary or immortalized cells, tissue explants, and animal models. Western blot was most commonly used to report phosphorylated (active) p38 MAPK. Human placenta (27), chorioamniotic membranes (14), myometrium (13), decidua (8), and cervix (1) were the studied tissues. p38 MAPK's functions were tissue and gestational age dependent. Isoform specificity was hardly reported. p38 MAPK activity was induced by ROS or proinflammatory cytokines to promote cell signaling linked to cell fate, primed uterus, ripened cervix, and proinflammatory cytokine/chemokine production. In 35 years, reports on p38 MAPK's role during pregnancy and parturition are scarce and current literature is insufficient to provide a comprehensive description of p38 MAPK's mechanistic role during pregnancy and parturition.
Topics: Animals; Disease Models, Animal; Female; Gene Expression Regulation; Genitalia, Female; Humans; Inflammation; Oxidative Stress; Parturition; Pregnancy; Reproduction; Signal Transduction; p38 Mitogen-Activated Protein Kinases
PubMed: 30178469
DOI: 10.1111/aji.13047 -
International Journal of Molecular... Aug 2018Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumours, and its incidence is rising worldwide. Although survival can be improved by surgical resection when these tumours are detected at an early stage, this cancer is usually asymptomatic, and disease only becomes apparent after metastasis. Several risk factors are associated with this disease, the most relevant being chronic pancreatitis, diabetes, tobacco and alcohol intake, cadmium, arsenic and lead exposure, certain infectious diseases, and the mutational status of some genes associated to a familial component. PDAC incidence has increased in recent decades, and there are few alternatives for chemotherapeutic treatment. Endoplasmic reticulum (ER) stress factors such as GRP78/BiP (78 kDa glucose-regulated protein), ATF6α (activating transcription factor 6 isoform α), IRE1α (inositol-requiring enzyme 1 isoform α), and PERK (protein kinase RNA-like endoplasmic reticulum kinase) activate the transcription of several genes involved in both survival and apoptosis. Some of these factors aid in inducing a non-proliferative state in cancer called dormancy. Modulation of endoplasmic reticulum stress could induce dormancy of tumour cells, thus prolonging patient survival. In this systematic review, we have compiled relevant results concerning those endoplasmic reticulum stress factors involved in PDAC, and we have analysed the mechanism of dormancy associated to endoplasmic reticulum stress and its potential use as a chemotherapeutic target against PDAC.
Topics: Activating Transcription Factor 6; Animals; Antibodies; Carcinoma, Pancreatic Ductal; Communicable Diseases; Deoxycytidine; Diabetes Complications; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Endoribonucleases; Gene Expression Regulation; Heat-Shock Proteins; Humans; Pancreatic Neoplasms; Pancreatitis, Chronic; Protein Serine-Threonine Kinases; RNA, Small Interfering; Risk Factors; Sulfones; eIF-2 Kinase; Gemcitabine
PubMed: 30134550
DOI: 10.3390/ijms19092468 -
Frontiers in Physiology 2018Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review...
Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review to identify genes whose experimental loss or gain-of-function results in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. They are from high to small effect size: . Knock out, knock down, overexpression or a higher activity of these genes causes overall muscle hypertrophy as measured by an increased muscle weight or cross sectional area. The mean effect sizes range from 5 to 345% depending on the manipulated gene as well as the muscle size variable and muscle investigated. Bioinformatical analyses reveal that are most highly expressed hypertrophy genes in human skeletal muscle when compared to other tissues. Many of the muscle hypertrophy-regulating genes are involved in transcription and ubiquitination. Especially genes belonging to three signaling pathways are able to induce hypertrophy: (a) Igf1-Akt-mTOR pathway, (b) myostatin-Smad signaling, and (c) the angiotensin-bradykinin signaling pathway. The expression of several muscle hypertrophy-inducing genes and the phosphorylation of their protein products changes after human resistance and high intensity exercise, in maximally stimulated mouse muscle or in overloaded mouse plantaris.
PubMed: 29910734
DOI: 10.3389/fphys.2018.00553 -
Molecular Genetics and Metabolism Mar 2019Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can...
BACKGROUND
Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease.
METHODS
A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients.
RESULTS
Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life.
CONCLUSIONS
Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage.
Topics: Child; Enzyme Replacement Therapy; Europe; Fabry Disease; Female; Humans; Isoenzymes; Male; Observational Studies as Topic; Pain; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome; Trihexosylceramides; alpha-Galactosidase
PubMed: 29785937
DOI: 10.1016/j.ymgme.2018.04.007 -
Cancer Oct 2018Although the majority of patients with chronic myeloid leukemia do well with treatment with tyrosine kinase inhibitors (TKIs), some patients still have inferior...
Although the majority of patients with chronic myeloid leukemia do well with treatment with tyrosine kinase inhibitors (TKIs), some patients still have inferior outcomes. There are many factors that might play a part, including the different BCR-ABL1 transcript types at baseline. The current study was performed to determine the possible impact of different transcripts on the treatment responses and outcomes of patients with chronic myeloid leukemia who are receiving TKI therapy. The authors performed a systematic literature search by using the terms "b2a2/b3a2," "e13a2/e14a2," or "transcript type." e14a2 was the more common transcript type. The majority of the studies demonstrated no significant difference regarding age, sex, leukocyte counts, and hemoglobin levels between patients with the e13a2 and e14a2 transcripts. However, in approximately one-half of the studies, the e14a2 transcript was associated with higher platelet counts. Almost no studies demonstrated a significant association between disease risk scores and transcript types. In the majority of studies, having the e14a2 transcript was associated with earlier, deeper, and higher molecular response rates. Although better event-free survival was observed in patients with the e14a2 transcript in some of the studies, the majority demonstrated that transcript type did not have an impact on progression-free and overall survival. Treatment-free remission currently is a topic of much interest, and to the authors' knowledge there are limited data with conflicting results regarding the possible effects of transcript types on the outcomes of patients after discontinuation of TKIs. Because having the e14a2 transcript appears to be related to a favorable outcome, choosing second-generation TKIs for frontline therapy might be a convenient approach in patients with chronic myeloid leukemia with the e13a2 transcript. The authors believe this finding warrants further investigation.
Topics: Antineoplastic Agents, Immunological; Biomarkers, Pharmacological; Biomarkers, Tumor; Fusion Proteins, bcr-abl; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Prognosis; Protein Isoforms; Protein Kinase Inhibitors; RNA, Messenger; Treatment Outcome
PubMed: 29694669
DOI: 10.1002/cncr.31408 -
Clinical Chemistry and Laboratory... Aug 2018The purpose of this systematic review is to summarize the literature examining associations between salivary biomarkers and cardiovascular disease (CVD) status.
BACKGROUND
The purpose of this systematic review is to summarize the literature examining associations between salivary biomarkers and cardiovascular disease (CVD) status.
CONTENTS
An advanced search was conducted using MeSH terms related to salivary biomarkers and CVD, and entered into the PubMed, Web of Science, and Google Scholar search databases. Four hundred and thirty-three records were narrowed to 22 accepted articles. Included titles were assessed for quality using the Newcastle-Ottawa scale, and ranked into categories of low, moderate, or high.
SUMMARY
A total of 40 salivary biomarkers were analyzed among accepted articles. The most studied markers were salivary creatine kinase isoform MB, C-reactive protein (CRP), matrix metalloproteinase-9, troponin I, myeloperoxidase, myoglobin, and brain natriuretic peptide. Salivary CRP provided the most consistent trends. Statistically significant increases of salivary CRP were present with CVD in every study that analyzed it. The remaining six markers demonstrated varying patterns.
OUTLOOK
Existing studies provide insufficient data to draw definitive conclusions. Current research shows that there is an association between some salivary biomarkers and CVD, but the details of existing studies are conflicting. Despite inconclusive results, the diagnostic potential of saliva shows promise as a non-invasive means of cardiovascular risk assessment.
Topics: Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Humans; Matrix Metalloproteinase 9; Saliva
PubMed: 29630504
DOI: 10.1515/cclm-2017-1018 -
Alzheimer's Research & Therapy Jan 2018The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with Alzheimer's...
BACKGROUND
The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with Alzheimer's disease-like clinical features.
METHODS
We compiled clinical data from a new Swedish kindred with R406W mutation. Seven family members were followed longitudinally for up to 22 years. Radiological examinations were performed in six family members and neuropathological examinations in three. We systematically reviewed the literature and compiled clinical, radiological, and neuropathological data on 63 previously described R406W heterozygotes and 3 homozygotes.
RESULTS
For all cases combined, the median age of onset was 56 years and the median disease duration was 13 years. Memory impairment was the most frequent symptom, behavioral disturbance and language impairment were less common, and Parkinsonism was rare. Disease progression was most often slow. The most frequent clinical diagnosis was Alzheimer's disease. R406W homozygotes had an earlier age at onset and a higher frequency of behavioral symptoms and Parkinsonism than heterozygotes. In the new Swedish kindred, a consistent imaging finding was ventromedial temporal lobe atrophy, which was evident also in early disease stages as a widening of the collateral sulcus with ensuing atrophy of the parahippocampal gyrus. Unlike previously published R406W carriers, all three autopsied patients from the novel family showed neuropathological similarities with progressive supranuclear palsy, with predominant four-repeat (exon 10+) tau isoform (4R) tauopathy and neurofibrillary tangles accentuated in the basal-medial temporal lobe. Amyloid-β pathology was absent.
CONCLUSIONS
Dominance of 4R over three-repeat (exon 10-) tau isoforms contrasts with earlier reports of R406W patients and was not sufficiently explained by the presence of H1/H2 haplotypes in two of the autopsied patients. R406W patients often show a long course of disease with marked memory deficits. Both our neuropathological results and our imaging findings revealed that the ventromedial temporal lobes were extensively affected in the disease. We suggest that this area may represent the point of origin of tau deposition in this disease with relatively isolated tauopathy.
Topics: Age of Onset; Aged; Brain; Dementia; Disease Progression; Family; Female; Humans; Longitudinal Studies; Male; Middle Aged; Mutation; tau Proteins
PubMed: 29370822
DOI: 10.1186/s13195-017-0330-2