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Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting a growing number of elderly people. In order to improve the early and differential diagnosis of AD, better biomarkers are needed. Glycosylation is a protein post-translational modification that is modulated in the course of many diseases, including neurodegeneration. Aiming to improve AD diagnosis and differential diagnosis through glycan analytics methods, we report the glycoprotein glycome of cerebrospinal fluid (CSF) isolated from a total study cohort of 262 subjects. The study cohort consisted of patients with AD, healthy controls and patients suffering from other types of dementia. CSF free-glycans were also isolated and analyzed in this study, and the results reported for the first time the presence of 19 free glycans in this body fluid. The free-glycans consisted of complete or truncated N-/O-glycans as well as free monosaccharides. The free-glycans Hex1 and HexNAc1Hex1Neu5Ac1 were able to discriminate AD from controls and from patients suffering from other types of dementia. Regarding CSF N-glycosylation, high proportions of high-mannose, biantennary bisecting core-fucosylated N-glycans were found, whereby only about 20% of the N-glycans were sialylated. O-Glycans and free-glycan fragments were less sialylated in AD patients than in controls. To conclude, this comprehensive study revealed for the first time the biomarker potential of free glycans for the differential diagnosis of AD.
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Doença de Alzheimer , Biomarcadores , Polissacarídeos , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Humanos , Biomarcadores/líquido cefalorraquidiano , Polissacarídeos/líquido cefalorraquidiano , Polissacarídeos/química , Masculino , Feminino , Idoso , Glicosilação , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Glicoproteínas/líquido cefalorraquidiano , Estudos de Casos e ControlesRESUMO
Patients with chronic kidney disease (CKD) have a high prevalence of hyperphosphatemia, where uremic toxins like inorganic phosphate (Pi) induce a cardiovascular remodeling. Related disorders like atherosclerosis bear the risk of increased morbidity and mortality. We previously found that Pi stimulates the synthesis and sulfation of the negatively charged glycosaminoglycans (GAGs) heparan sulfate and chondroitin sulfate in vascular smooth muscle cells (VSMC). Similar GAG alterations were detected in VSMC-derived exosome-like extracellular vesicles (EV). These EV showed a strong interaction with very small superparamagnetic iron oxide particles (VSOP), which are used as imaging probes for experimental magnetic resonance imaging (MRI). Hyaluronic acid (HA) represents another negatively charged GAG which is supposed to function as binding motif for VSOP as well. We investigated the effects of Pi on the amounts of HA in cells and EV and studied the HA-dependent interaction between VSOP with cells and EV. Rat VSMC were treated with elevated concentrations of Pi. CKD in rats was induced by adenine feeding. EV were isolated from culture supernatants and rat plasma. We investigated the role of HA in binding VSOP to cells and EV via cell-binding studies, proton relaxometry, and analysis of cellular signaling, genes, proteins, and HA contents. Due to elevated HA contents, VSMC and EV showed an increased interaction with VSOP after Pi stimulation. Amongst others, Pi induced hyaluronan synthase (HAS)2 expression and activation of the Wnt pathway in VSMC. An alternative upregulation of HA by iloprost and an siRNA-mediated knockdown of HAS2 confirmed the importance of HA in cells and EV for VSOP binding. The in vitro-derived data were validated by analyses of plasma-derived EV from uremic rats. In conclusion, the inorganic uremic toxin Pi induces HA synthesis in cells and EV, which leads to an increased interaction with VSOP. HA might therefore be a potential molecular target structure for improved detection of pathologic tissue changes secondary to CKD like atherosclerosis or cardiomyopathy using EV, VSOP and MRI.
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Aterosclerose , Vesículas Extracelulares , Compostos Férricos , Insuficiência Renal Crônica , Humanos , Animais , Ratos , Ácido Hialurônico , Fosfatos , Músculo Liso Vascular , Nanopartículas Magnéticas de Óxido de FerroRESUMO
Guanosine diphosphate-mannose pyrophosphorylase B (GMPPB) catalyzes the conversion of mannose-1-phosphate and GTP to GDP-mannose, which is required as a mannose donor for the biosynthesis of glycan structures necessary for proper cellular functions. Mutations in GMPPB have been associated with various neuromuscular disorders such as muscular dystrophy and myasthenic syndromes. Here, we report that GMPPB protein abundance increases during brain and skeletal muscle development, which is accompanied by an increase in overall protein mannosylation. To model the human disorder in mice, we generated heterozygous GMPPB KO mice using CIRSPR/Cas9. While we were able to obtain homozygous KO mice from heterozygous matings at the blastocyst stage, homozygous KO embryos were absent beyond embryonic day E8.5, suggesting that the homozygous loss of GMPPB results in early embryonic lethality. Since patients with GMPPB loss-of-function manifest with neuromuscular disorders, we investigated the role of GMPPB in vitro. Thereby, we found that the siRNA-mediated knockdown of Gmppb in either primary myoblasts or the myoblast cell line C2C12 impaired myoblast differentiation and resulted in myotube degeneration. siRNA-mediated knockdown of Gmppb also impaired the neuron-like differentiation of N2A cells. Taken together, our data highlight the essential role of GMPPB during development and differentiation, especially in myogenic and neuronal cell types.
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OBJECTIVES: Our objectives were to evaluate the impact of group pelvic floor education workshops on participants' knowledge, their satisfaction, and the modification of their urinary and digestive behaviors, and to compare health care providers' (HCP) knowledge with that of the general population. METHODS: For this prospective observational study, group pelvic floor education workshops were proposed between May 2021 and June 2022 in a web-conference format. Each workshop covered pelvic floor anatomy and physiology, urinary and digestive physiology as well as risk factors of PFD and preventive measures. At the start and the end of the workshops, participants completed a questionnaire on their knowledge and their beliefs about the pelvic floor. Questions about their satisfaction were asked at the end of the workshops. A 2-month questionnaire assessed changes in urinary and digestive habits and whether participants had talked about the workshop around them. RESULTS: A total of 856, with an average age 40.1 years, participated and completed the questionnaires before and after the workshops; 694 responded at 2 months. The education workshops significantly improved knowledge about the pelvic floor in the "HCP" and "non-HCP" groups. At 2 months, 591 participants (85.2%) 85.2% had talked about the workshop content; 557 (80.3%) reported having changed, or planned to change, their urinary behaviors and 495 (71.3%) their defecatory behaviors. CONCLUSIONS: Pelvic floor education workshops can increase level of knowledge and thus limit risky behaviors for the pelvic floor. The high rate of participation and the satisfaction of the participants shows the interest for the theme.
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Distúrbios do Assoalho Pélvico , Prolapso de Órgão Pélvico , Adulto , Feminino , Humanos , Escolaridade , Hábitos , Estilo de Vida , Diafragma da Pelve , Distúrbios do Assoalho Pélvico/prevenção & controle , Inquéritos e Questionários , Estudos ProspectivosRESUMO
Protein glycosylation, a complex and heterogeneous post-translational modification that is frequently dysregulated in disease, has been difficult to analyse at scale. Here we report a data-independent acquisition technique for the large-scale mass-spectrometric quantification of glycopeptides in plasma samples. The technique, which we named 'OxoScan-MS', identifies oxonium ions as glycopeptide fragments and exploits a sliding-quadrupole dimension to generate comprehensive and untargeted oxonium ion maps of precursor masses assigned to fragment ions from non-enriched plasma samples. By applying OxoScan-MS to quantify 1,002 glycopeptide features in the plasma glycoproteomes from patients with COVID-19 and healthy controls, we found that severe COVID-19 induces differential glycosylation in IgA, haptoglobin, transferrin and other disease-relevant plasma glycoproteins. OxoScan-MS may allow for the quantitative mapping of glycoproteomes at the scale of hundreds to thousands of samples.
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COVID-19 , Glicopeptídeos , Humanos , Espectrometria de Massas , Glicosilação , Glicopeptídeos/análise , Glicopeptídeos/química , Glicopeptídeos/metabolismo , ÍonsRESUMO
It remains uncertain how brain glycosaminoglycans (GAGs) contribute to the progression of inflammatory disorders like multiple sclerosis (MS). We investigated here neuroinflammation-mediated changes in GAG composition and metabolism using the mouse model of experimental autoimmune encephalomyelitis (EAE) and sham-immunized mice as controls. Cerebellum, mid- and forebrain at different EAE phases were investigated using gene expression analysis (microarray and RT-qPCR) as well as HPLC quantification of CS and hyaluronic acid (HA). The cerebellum was the most affected brain region showing a downregulation of Bcan, Cspg5, and an upregulation of Dse, Gusb, Hexb, Dcn and Has2 at peak EAE. Upregulation of genes involved in GAG degradation as well as synthesis of HA and decorin persisted from onset to peak, and diminished at remission, suggesting a severity-related decrease in CS and increments in HA. Relative disaccharide quantification confirmed a 3.6 % reduction of CS-4S at peak and a normalization during remission, while HA increased in both phases by 26.1 % and 17.6 %, respectively. Early inflammatory processes led to altered GAG metabolism in early EAE stages and subsequent partially reversible changes in CS-4S and in HA. Targeting early modifications in CS could potentially mitigate progression of EAE/MS.
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Encefalite , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Ácido Hialurônico/farmacologia , Glicosaminoglicanos/metabolismo , Encefalomielite Autoimune Experimental/genética , Sulfatos de Condroitina/metabolismoRESUMO
Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T2* weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, co-localization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content.
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Ovarian cancer (OC) is a gynecological malignancy characterized by high morbidity and mortalities due to late-stage diagnosis because accurate early diagnostic biomarkers are lacking. Testing of Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human immunodeficiency virus (HIV) infections in OC patients is pertinent in light of the emerging evidence of their contribution to poor prognosis. We, for the first time, investigated the prevalence of HBV, HCV, and HIV infections in a Kenyan cohort of OC to inform optimal management. We recruited a cohort of women above 18 years of age, comprising 86 OC patients and 50 healthy controls. Participants' blood samples were serologically screened for HBV, HCV, and HIV. We found seroprevalence rates of 29.1%, 26.7%, and 1.2% for HBV, HIV, and HCV, respectively, in OC patients. The healthy control group had HBV and HIV seroprevalence rates of 3.9% for each with no positive HCV case. HBV/HIV coinfection was noted only in the OC group with a positivity rate of 17.4%. In summary, we found higher HBV and HIV seroprevalence in Kenyan OC patients compared to the healthy control group, whereas HCV prevalence was reflective of the general population. Hence, we recommend screening for HBV and HIV among OC patients destined for anticancer treatment.
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The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been affecting the world since January 2020 and has caused millions of deaths. To gain a better insight into molecular changes underlying the COVID-19 disease, we investigated here the N-glycosylation of three immunoglobulin G (IgG) fractions isolated from plasma of 35 severe COVID-19 patients, namely total IgG1, total IgG2, and anti-Spike IgG, by means of MALDI-TOF-MS. All analyses were performed at the glycopeptide level to assure subclass- and site-specific information. For each COVID-19 patient, the analyses included three blood withdrawals at different time-points of hospitalization, which allowed profiling longitudinal alterations in IgG glycosylation. The COVID-19 patients presented altered IgG N-glycosylation profiles in all investigated IgG fractions. The most pronounced COVID-19-related changes were observed in the glycosylation profiles of antigen-specific anti-Spike IgG1. Anti-Spike IgG1 fucosylation and galactosylation showed the strongest variation during the disease course, with the difference in anti-Spike IgG1 fucosylation being significantly correlated with patients' age. Decreases in anti-Spike IgG1 galactosylation and sialylation in the course of the disease were found to be significantly correlated with the difference in anti-Spike IgG plasma concentration. The present findings suggest that patients' age and anti-S IgG abundance might influence IgG N-glycosylation alterations occurring in COVID-19.
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Glycosaminoglycans (GAGs) are considered to be the most difficult type of glycoconjugates to analyze as they are constituted of linear long polysaccharidic chains having molecular weights reaching up to several million daltons. Bottom-up analysis of glycosaminoglycans from biological samples is a long and work-extensive procedure due to the many preparation steps involved. In addition, so far, only few research articles have been dedicated to the analysis of GAGs by means of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) because their intact ionization can be problematic due to the presence of labile sulfate groups. In this work, we had the aim of exploring the sulfation pattern of monosulfated chondroitin/dermatan sulfate (CS/DS) disaccharides in human tissue samples because they represent the most abundant form of sulfation in disaccharides. We present here an optimized strategy to analyze on-target derivatized CS/DS disaccharides via MALDI-TOF-MS using a fast workflow that does not require any purification after enzymatic cleavage. For the first time, we show that MALDI-TOF/TOF experiments allow for discrimination between monosulfated CS disaccharide isomers via specific fragments corresponding to glycosidic linkages and to cross-ring cleavages. This proof of concept is illustrated via the analysis of CS/DS disaccharides of atherosclerotic lesions of different histological origins, in which we were able to identify their monosulfation patterns.
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The particularly high mortality of epithelial ovarian cancer (EOC) is in part linked to limited understanding of its molecular signatures. Although there are data available on in situ N-glycosylation in EOC tissue, previous studies focused primarily on neutral N-glycan species and, hence, still little is known regarding EOC tissue-specific sialylation. In this proof-of-concept study, we implemented MALDI mass spectrometry imaging (MALDI-MSI) in combination with sialic acid derivatization to simultaneously investigate neutral and sialylated N-glycans in formalin-fixed paraffin-embedded tissue microarray specimens of less common EOC histotypes and non-malignant borderline ovarian tumor (BOT). The applied protocol allowed detecting over 50 m/z species, many of which showed differential tissue distribution. Most importantly, it could be demonstrated that α2,6- and α2,3-sialylated N-glycans are enriched in tissue regions corresponding to tumor and adjacent tumor-stroma, respectively. Interestingly, analogous N-glycosylation patterns were observed in tissue cores of BOT, suggesting that regio-specific N-glycan distribution might occur already in non-malignant ovarian pathologies. All in all, our data provide proof that the combination of MALDI-MSI and sialic acid derivatization is suitable for delineating regio-specific N-glycan distribution in EOC and BOT tissues and might serve as a promising strategy for future glycosylation-based biomarker discovery studies.
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Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum (Pf) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf-derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf-infected RBCs carry significantly higher sialylated complex N-glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N-glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N-glycans to mediate EV uptake by the human immune system cells.
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Glycosaminoglycans are long polysaccharidic chains, which are mostly present in connective tissues. Modified GAG expression in tissues surrounding malignant cells has been shown to contribute to tumor progression, aggressive status and metastasis in many types of cancer. Ovarian cancer is one of the most lethal gynecological malignancies due to its late diagnosis because of the absence of clear symptoms and unavailability of early disease markers. We investigated for the first time GAG changes at the molecular level as a novel biomarker for primary epithelial ovarian cancer. To this end, serum of a cohort of 68 samples was digested with chondroitinase ABC, which releases chondroitin sulfate into disaccharides. After labeling and purification, they were measured by HPLC, yielding a profile of eight disaccharides. We proposed a novel GAG-based score named "CS- bio" from the measured abundance of disaccharides present that were of statistical relevance. CS-bio's performance was compared with CA125, the clinically used serum tumor marker in routine diagnostics. CS-bio had a better sensitivity and specificity than CA125. It was more apt in differentiating early-stage patients from healthy controls, which is of high interest for oncologists.
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BACKGROUND AND AIMS: The YAP/TAZ signaling is known to regulate endothelial activation and vascular inflammation in response to shear stress. Moreover, YAP/TAZ signaling plays a role in the progression of cancers and renal damage associated with diabetes. However, whether YAP/TAZ signaling is also implicated in diabetes-associated vascular complications is not known. METHODS: The effect of high glucose on YAP/TAZ signaling was firstly evaluated in vitro on endothelial cells cultured under static conditions or subjected to shear stress (either laminar or oscillatory flow). The impact of diabetes on YAP/TAZ signaling was additionally assessed in vivo in db/db mice. RESULTS: In vitro, we found that YAP was dephosphorylated/activated by high glucose in endothelial cells, thus leading to increased endothelial inflammation and monocyte attachment. Moreover, YAP was further activated when high glucose was combined to laminar flow conditions. YAP was also activated by oscillatory flow conditions but, in contrast, high glucose did not exert any additional effect. Interestingly, inhibition of YAP reduced endothelial inflammation and monocyte attachment. Finally, we found that YAP is also activated in the vascular wall of diabetic mice, where inflammatory markers are also increased. CONCLUSION: With the current study we demonstrated that YAP signaling is activated by high glucose in endothelial cells in vitro and in the vasculature of diabetic mice, and we pinpointed YAP as a regulator of high glucose-mediated endothelial inflammation and monocyte attachment. YAP inhibition may represent a potential therapeutic opportunity to improve diabetes-associated vascular complications.
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Cardiovascular disease is one of the leading causes of death in developed countries. Because the incidence increases exponentially in the aging population, aging is a major risk factor for cardiovascular disease. Cardiac hypertrophy, fibrosis and inflammation are typical hallmarks of the aged heart. The molecular mechanisms, however, are poorly understood. Because glycosylation is one of the most common post-translational protein modifications and can affect biological properties and functions of proteins, we here provide the first analysis of the cardiac glycoproteome of mice at different ages. Western blot as well as MALDI-TOF based glycome analysis suggest that high-mannose N-glycans increase with age. In agreement, we found an age-related regulation of GMPPB, the enzyme, which facilitates the supply of the sugar-donor GDP-mannose. Glycoprotein pull-downs from heart lysates of young, middle-aged and old mice in combination with quantitative mass spectrometry bolster widespread alterations of the cardiac glycoproteome. Major hits are glycoproteins related to the extracellular matrix and Ca2+-binding proteins of the endoplasmic reticulum. We propose that changes in the heart glycoproteome likely contribute to the age-related functional decline of the cardiovascular system.
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SARS-CoV-2 causes the respiratory syndrome COVID-19 and is responsible for the current pandemic. The S protein of SARS-CoV-2-mediating virus binding to target cells and subsequent viral uptake is extensively glycosylated. Here we focus on how glycosylation of both SARS-CoV-2 and target cells crucially impacts SARS-CoV-2 infection at different levels: (1) virus binding and entry to host cells, with glycosaminoglycans of host cells acting as a necessary co-factor for SARS-CoV-2 infection by interacting with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein, (2) innate and adaptive immune response where glycosylation plays both a protective role and contributes to immune evasion by masking of viral polypeptide epitopes and may add to the cytokine cascade via non-fucosylated IgG, and (3) therapy and vaccination where a monoclonal antibody-neutralizing SARS-CoV-2 was shown to interact also with a distinct glycan epitope on the SARS-CoV-2 spike protein. These evidences highlight the importance of ensuring that glycans are considered when tackling this disease, particularly in the development of vaccines, therapeutic strategies and serological testing.
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COVID-19/metabolismo , Interações Hospedeiro-Patógeno , SARS-CoV-2/fisiologia , Imunidade Adaptativa , Animais , Antígenos de Grupos Sanguíneos/imunologia , Antígenos de Grupos Sanguíneos/metabolismo , COVID-19/imunologia , COVID-19/terapia , Exocitose , Glicosilação , Humanos , Imunidade Inata , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus , Replicação ViralRESUMO
Ovarian cancer remains one of the most common causes of death among gynecological malignancies afflicting women worldwide. Among the gynecological cancers, cervical and endometrial cancers confer the greatest burden to the developing and the developed world, respectively; however, the overall survival rates for patients with ovarian cancer are worse than the two aforementioned. The majority of patients with ovarian cancer are diagnosed at an advanced stage when cancer has metastasized to different body sites and the cure rates, including the five-year survival, are significantly diminished. The delay in diagnosis is due to the absence of or unspecific symptoms at the initial stages of cancer as well as a lack of effective screening and diagnostic biomarkers that can detect cancer at the early stages. This, therefore, provides an imperative to prospect for new biomarkers that will provide early diagnostic strategies allowing timely mitigative interventions. Glycosylation is a protein post-translational modification that is modified in cancer patients. In the current review, we document the state-of-the-art of blood-based glycomic biomarkers for early diagnosis of ovarian cancer and the technologies currently used in this endeavor.
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GDP-mannose-pyrophosphorylase-B (GMPPB) facilitates the generation of GDP-mannose, a sugar donor required for glycosylation. GMPPB defects cause muscle disease due to hypoglycosylation of α-dystroglycan (α-DG). Alpha-DG is part of a protein complex, which links the extracellular matrix with the cytoskeleton, thus stabilizing myofibers. Mutations of the catalytically inactive homolog GMPPA cause alacrima, achalasia, and mental retardation syndrome (AAMR syndrome), which also involves muscle weakness. Here, we showed that Gmppa-KO mice recapitulated cognitive and motor deficits. As structural correlates, we found cortical layering defects, progressive neuron loss, and myopathic alterations. Increased GDP-mannose levels in skeletal muscle and in vitro assays identified GMPPA as an allosteric feedback inhibitor of GMPPB. Thus, its disruption enhanced mannose incorporation into glycoproteins, including α-DG in mice and humans. This increased α-DG turnover and thereby lowered α-DG abundance. In mice, dietary mannose restriction beginning after weaning corrected α-DG hyperglycosylation and abundance, normalized skeletal muscle morphology, and prevented neuron degeneration and the development of motor deficits. Cortical layering and cognitive performance, however, were not improved. We thus identified GMPPA defects as the first congenital disorder of glycosylation characterized by α-DG hyperglycosylation, to our knowledge, and we have unraveled underlying disease mechanisms and identified potential dietary treatment options.
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Distroglicanas , Guanosina Difosfato Manose , Músculo Esquelético/metabolismo , Doenças Neuromusculares , Nucleotidiltransferases/deficiência , Animais , Distroglicanas/genética , Distroglicanas/metabolismo , Glicosilação , Guanosina Difosfato Manose/genética , Guanosina Difosfato Manose/metabolismo , Humanos , Camundongos , Camundongos Knockout , Doenças Neuromusculares/dietoterapia , Doenças Neuromusculares/genética , Doenças Neuromusculares/metabolismo , Nucleotidiltransferases/metabolismoRESUMO
OBJECTIVE: We aimed to assess the impact of an educational program on the symptoms and quality of life of patients undergoing supervised pelvic floor muscle training (PFMT). Secondary objectives included: baseline assessment of patients' knowledge of the pelvic floor; and patient satisfaction and symptom improvement after the entire PFMT program. MATERIAL AND METHODS: An observational questionnaire-based study in women attending a PFMT program consisting of four educational sessions, one visual feedback session, and five personalized training sessions. The patients completed the questionnaire at baseline, after the four educational sessions and then after completion of program. The questionnaires included the ICIQ-SF, USP, Contilife, PFDI 20, Kess and Wexner scores. Additional questions were added before treatment about the patient's knowledge of the pelvic floor. RESULTS: Seventy-nine women were included. Improvement in symptoms was significant after the four educational sessions: mean PFDI-20 score decreased from 68.5-29.5 (p < 0.05); ICIQ-SF score from 8.0-3.1 (p < 0.05), Wexner and Kess scores from 8.2-6.5 and from 13.3-10 (p < 0.05). Symptom scores were also all significantly improved on completion of the program. After the four educational sessions, 50 of the 68 patients (73.5 %) with complete questionnaires reported feeling better or much better. Only 12 (15.2 %) women overall located the pelvic floor across the entire bottom of the pelvis. CONCLUSION: This preliminary study suggests that four educational sessions can improve symptoms and quality of life before PFM reinforcement itself. If confirmed by larger prospective studies, a solid educational element should be systematically integrated in all PFMT programs.