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1.
J. Health Biol. Sci. (Online) ; 10(1): 1-4, 01/jan./2022.
Artigo em Inglês | LILACS | ID: biblio-1369163

RESUMO

Introduction: One of the challenges of maxillofacial surgery is the rehabilitation of patients with severe bone loss, using implant-supported prostheses. This challenge is based on the small remaining bone structure, and on the need to reconstruct the structure for the rehabilitation with autogenous or exogenous grafts. Case report: We report the case of a patient with severe maxillary atrophy, where a skullcap graft was performed associated with implant placement and prosthetic completion 14 months after the start of treatment. Final considerations: We demonstrate clinical safety for the use of extraoral grafts without complications, representing a good alternative treatment for this group of patients.


Introdução: um dos desafios da cirurgia bucomaxilofacial é a reabilitação de pacientes com perda óssea severa, utilizando próteses implantossuportadas. Este desafio baseia-se na pequena estrutura óssea remanescente e na necessidade de reconstrução da estrutura para a reabilitação com enxertos autógenos ou exógenos. Relato de caso: Relatamos o caso de um paciente com atrofia maxilar grave, onde foi realizado enxerto de calota craniana associado à instalação de implante, com finalização protética 14 meses após o início do tratamento. Consideracoes finais: Demonstramos segurança clínica para o uso de enxertos extrabucais sem complicações, representando uma boa alternativa de tratamento para este grupo de pacientes.


Assuntos
Mandíbula , Pacientes , Próteses e Implantes , Atrofia , Crânio , Cirurgia Bucal , Arcada Edêntula
2.
ASN Neuro ; 14: 17590914221099112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35503242

RESUMO

Traumatic brain injury (TBI) has consequences that last for years following injury. While TBI can precipitate a variety of diffuse pathologies, the mechanisms involved in injury-induced neuronal membrane disruption remain elusive. The lysosomal cysteine protease, Cathepsin B (Cath B), and specifically its redistribution into the cytosol has been implicated in cell death. Little is known about Cath B or neuronal membrane disruption chronically following diffuse TBI. Therefore, the current study evaluated Cath B and diffuse neuronal membrane disruption over a more chronic post-injury window (6 h-4 w). We evaluated Cath B in adult male Sprague-Dawley rats following central fluid percussion injury (CFPI). Expression of Cath B, as well as Cath B-associated pro (Bak and AIF) and anti-apoptotic (Bcl-xl) proteins, were assessed using western blot analysis. Cath B activity was also assessed. Localization of Cath B was evaluated in the membrane disrupted and non-disrupted population following CFPI using immunohistochemistry paired with quantitative image analysis and ultrastructural verification. There was no difference in expression or activity of Cath B or any of the associated proteins between sham and CFPI at any time post-injury. Immunohistological studies, however, showed a sub-cellular re-localization of Cath B at 2 w and 4 w post-injury in the membrane disrupted neuronal population as compared to the time-point matched non-disrupted neurons. Both membrane disruption and Cath B relocalization appear linked to neuronal atrophy. These observations are indicative of a late secondary pathology that represents an opportunity for therapeutic treatment of these neurons following diffuse TBI. Summary Statement Lysosomal cathepsin B relocalizes to the cytosol in neurons with disrupted plasmalemmal membranes weeks following diffuse brain injury. Both the membrane disrupted and cathepsin B relocalized neuronal subpopulations displayed smaller soma and nucleus size compared to non-pathological neurons, indicating atrophy.


Assuntos
Lesões Encefálicas Difusas , Lesões Encefálicas Traumáticas , Animais , Atrofia/metabolismo , Atrofia/patologia , Lesões Encefálicas Difusas/metabolismo , Lesões Encefálicas Difusas/patologia , Lesões Encefálicas Traumáticas/patologia , Catepsina B/análise , Catepsina B/metabolismo , Masculino , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley
3.
Nat Commun ; 13(1): 2370, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501350

RESUMO

Decline in skeletal muscle cell size (myofiber atrophy) is a key feature of cancer-induced wasting (cachexia). In particular, atrophy of the diaphragm, the major muscle responsible for breathing, is an important determinant of cancer-associated mortality. However, therapeutic options are limited. Here, we have used Drosophila transgenic screening to identify muscle-secreted factors (myokines) that act as paracrine regulators of myofiber growth. Subsequent testing in mouse myotubes revealed that mouse Fibcd1 is an evolutionary-conserved myokine that preserves myofiber size via ERK signaling. Local administration of recombinant Fibcd1 (rFibcd1) ameliorates cachexia-induced myofiber atrophy in the diaphragm of mice bearing patient-derived melanoma xenografts and LLC carcinomas. Moreover, rFibcd1 impedes cachexia-associated transcriptional changes in the diaphragm. Fibcd1-induced signaling appears to be muscle selective because rFibcd1 increases ERK activity in myotubes but not in several cancer cell lines tested. We propose that rFibcd1 may help reinstate myofiber size in the diaphragm of patients with cancer cachexia.


Assuntos
Caquexia , Neoplasias , Animais , Atrofia/metabolismo , Caquexia/metabolismo , Humanos , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Neoplasias/complicações , Neoplasias/genética , Neoplasias/metabolismo , Receptores de Superfície Celular/metabolismo
4.
Transl Neurodegener ; 11(1): 26, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35501886

RESUMO

BACKGROUND: Patient-to-patient variability in the degree to which ß-amyloid, tau and neurodegeneration impact cognitive decline in Alzheimer's disease (AD) complicates disease modeling and treatment. However, the underlying mechanisms leading to cognitive resilience are not resolved. We hypothesize that the variability in cognitive function and loss relates to neuronal resilience of the hippocampal GABAergic network. METHODS: We compared TgF344-AD and non-transgenic littermate rats at 9, 12, and 15 months of age. Neurons, ß-amyloid plaques and tau inclusions were quantified in hippocampus and entorhinal cortex. Somatostatin (SST) and parvalbumin (PVB) interneurons were traced to examine hippocampal neuroplasticity and cognition was tested in the Barnes maze. RESULTS: The 9-month-old TgF344-AD rats exhibited loss of neurons in the entorhinal cortex and hippocampus. Hippocampal neuronal compensation was observed in 12-month TgF344-AD rats, with upregulation of GABAergic interneuronal marker. By 15 months, the TgF344-AD rats had robust loss of excitatory and inhibitory neurons. ß-Amyloid and tau pathology accumulated continuously across age. SST interneurons exhibited tau inclusions and atrophy from 9 months, whereas PVB interneurons were resilient until 15 months. The hippocampal PVB circuit underwent neuroplastic reorganization with increased dendritic length and complexity in 9- and 12-month-old TgF344-AD rats, before atrophy at 15 months. Strikingly, 12-month-old TgF344-AD rats were resilient in executive function and cognitive flexibility. Cognitive resilience in TgF344-AD rats occurred as maintenance of function between 9 and 12 months of age despite progressive spatial memory deficits, and was sustained by PVB neuroplasticity. CONCLUSIONS: Our results demonstrate the inherent neuronal processes leading to cognitive maintenance, and describe a novel finding of endogenous cognitive resilience in an AD model.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Animais , Atrofia/complicações , Cognição , Modelos Animais de Doenças , Humanos , Plasticidade Neuronal , Parvalbuminas , Placa Amiloide/complicações , Ratos , Ratos Endogâmicos F344 , Ratos Transgênicos , Somatostatina
5.
Oxid Med Cell Longev ; 2022: 2093822, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528506

RESUMO

Currently, aquatic and terrestrial ecosystems are continuously and chronically polluted by cocktails of countless chemical compounds. The susceptibility to infections is tremendously increasing in a variety of organisms due to exposure to environmental pollutants. Pendimethalin, an herbicide, is continuously used in agriculture to remove unwanted broadleaf weeds across the globe. Therefore, this study investigates the mechanisms of toxicity of pendimethalin in freshwater fish bighead carp upon exposure to low and environmentally relevant concentrations. For this purpose, 48 fish without any clinical abnormalities were kept in a glass aquarium in different experimental groups (T0, T1, T2, and T3). These groups were treated with pendimethalin at 0.00, 0.25, 0.50, and 0.75 mg/L, respectively. Four fish were randomly picked from each experimental group and killed at 72, 96, and 120 hours of the trial to study hematobiochemical parameters and visceral tissues including the brain, liver, heart, gills, and kidneys for histopathology. Herbicide-treated fish indicated various physical and behavioral abnormalities including hypersecretion of mucus, erratic swimming, operculum movement, air gulping, tremors of fins, loss of equilibrium, and increased surface breathing. Histopathologically, gills tissues of treated fish indicated atrophied lamellae, uplifting of secondary lamellae, necrosis of primary and secondary lamellar epithelial cells, telogenesis, congestion, and lamellar fusion. Histopathological examination of liver tissues of treated fish showed mild to moderate congestion, necrosis of hepatocytes, and atrophy of hepatocytes while kidneys revealed degeneration of renal tubules, glomerular atrophy, ceroid, and necrosis of renal tubules. The erythrocyte counts, monocyte and lymphocyte counts, and hemoglobin values were significantly (P < 0.05) reduced in pendimethalin-treated fish. Results on serum biochemistry showed that the biomarkers of kidneys, heart, and liver were significantly higher in fish of treated groups. In addition, values of different biochemical reactions like reactive oxygen species (ROS), thiobarbituric acid reactive species (TBARS), total proteins, and quantity of different antioxidant enzymes including reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were significantly different when compared to untreated fish. Moreover, the percentile of different nuclear abnormalities in red blood cells and frequency of DNA damage increased significantly in treated fish. It can be concluded from the findings that pendimethalin causes its toxic effects via disruption of physiological and hematobiochemical reactions of fish.


Assuntos
Compostos de Anilina , Carpas , Herbicidas , Poluentes Químicos da Água , Compostos de Anilina/toxicidade , Animais , Atrofia , Carpas/metabolismo , Catalase/metabolismo , Ecossistema , Água Doce , Herbicidas/toxicidade , Fígado/metabolismo , Mutagênicos , Necrose/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/toxicidade
6.
Artigo em Chinês | MEDLINE | ID: mdl-35545594

RESUMO

Objective: Objective to investigate the health changes of patients with severe trimethyltin chloride (TMT) poisoning in four years. Methods: Six patients with severe TMT poisoning treated in the First Affiliated Hospital of Gannan Medical College in August 2016 were numbered 1, 2, 3, 4, 5 and 6 respectively. The patients were followed up 0.5, 2 and 4 years after poisoning and compared and analyzed. The follow-up contents include: symptom degree, score of simple mental intelligence examination scale (MMSE) and modified Rankin Scale (MRS) , cranial magnetic resonance imaging (MRI) , EEG, etc. Results: The symptoms of dizziness, headache, chest tightness, palpitation, nausea and vomiting decreased gradually in 6 patients. The symptoms of speech disorder and memory decline in No.1, 2 and 3 patients gradually increased, and the scores of MMSE and Mrs gradually decreased; Patients No.4, 5 and 6 had improved speech disorder, but their memory decreased, MMSE and Mrs scores were still flat, and mild cognitive impairment. The brain atrophy of No.1, 2 and 3 patients was aggravated, which showed obvious atrophy of hippocampus, temporal lobe, insular lobe and cerebellum and enlargement of ventricle; There was no significant change in brain atrophy in No.4, 5 and 6 patients. Conclusion: The neurotoxic symptoms in the later stage of severe TMT poisoning are still serious, and the neurotoxic time is long.


Assuntos
Compostos de Trimetilestanho , Atrofia , Seguimentos , Humanos , Imageamento por Ressonância Magnética
7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(2): 208-212, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35538754

RESUMO

Objective To study the influence of recombinant bovine basic fibroblast growth factor as an adjuvant therapy on scar alleviation and inflammatory cytokines in patients with atrophic acne scar. Methods The random number table was employed to randomly assign 120 patients with atrophic acne scar into a test group and a control group.Both groups of patients were treated with CO2 lattice laser.After the operation,the control group was routinely smeared with erythromycin ointment and the test group was coated with recombinant bovine basic fibroblast growth factor gel.The clinical efficacy,clinical indicators,scar alleviation,and inflammatory cytokine levels before and after treatment were compared,and adverse reactions were counted. Results The test group had higher total effective rate(P=0.040) and lower total incidence of adverse reactions(P=0.028) than the control group.Compared with the control group,the test group showcased short erythema duration after treatment(P=0.025),early scab forming(P=0.002),and early edema regression(P<0.001).After treatment,the proportion of grade 1 scars graded by Goodman and Baron's acne scar grading system in the test group and control group increased(P=0.001,P=0.027),and the proportion of grade 4 scars decreased(P<0.001,P=0.034).Moreover,the proportion of grade 1 scars in the test group was higher than that in the control group(P=0.031) after treatment,and the proportion of grade 4 scars presented an opposite trend(P=0.031).After treatment,the levels of tumor necrosis factor-α(TNF-α) and interleukin-1ß(IL-1ß) in both groups declined(all P<0.001),and the test group had lower TNF-α and IL-1ß levels than the control group(all P<0.001). Conclusion The recombinant bovine basic fibroblast growth factor gel as an adjuvant therapy of CO2 lattice laser can effectively alleviate the atrophic acne scar,relieve local inflammatory reaction,and has good curative effect and less adverse reactions.


Assuntos
Acne Vulgar , Cicatriz , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Animais , Atrofia/complicações , Dióxido de Carbono , Bovinos , Cicatriz/tratamento farmacológico , Cicatriz/etiologia , Cicatriz/patologia , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Humanos , Resultado do Tratamento , Fator de Necrose Tumoral alfa
8.
Wiad Lek ; 75(3): 664-669, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35522876

RESUMO

OBJECTIVE: The aim: To study the topographic variability of the left and right mandibular canals in case of bone atrophy caused by the loss of the masticatory teeth. PATIENTS AND METHODS: Materials and methods: 136 digital scans were selected for morphometric analysis, 68 for each side taken with the Vatech PaX-i 3D Green extra-oral radiography system. The readout of absolute morphometric values, laying the left and right MC was performed in the projection of 3.7, 3.6, 4.6, 4.7 teeth using standardized Ez3D-I software. RESULTS: Results: The alveolar part is characterized by distance to the alveolar ridge, and primarily exposed to pronounced atrophic processes of bone tissue. Distance to the lingual ridge directly proportionally indicates the morphological transposition vector of the mandibular canals for the distance to the buccal ridge, by the same length to its reduction. Morphometric analysis on a short toothless segment determines the variability of laying the mandibular canals but it is characterized by constant regular values of the ridge of the mandibular base. CONCLUSION: Conclusions: Dentition defects, moving towards the missing teeth, lead to a decrease in the biophysical stimulus on bone tissue, causing pronounced morphological changes with the loss of significant volume and restructuring of its trabecular layer, which synchronously affects the topographic variability of the left and right MC.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Processo Alveolar , Atrofia/patologia , Humanos , Mandíbula/diagnóstico por imagem , Radiografia
9.
Rom J Ophthalmol ; 66(1): 79-83, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531456

RESUMO

Objective: To describe the development of retinal pigment epithelium (RPE) atrophy after uncomplicated pars plana vitrectomy (PPV) with epiretinal membrane (ERM) and/or internal limiting membrane (ILM) peeling in 2 patients. Cases description: Case 1: A 79-years-old female with diagnosis of a full-thickness macular hole in her right eye (OD) with best corrected visual acuity (BCVA) of: 20/100 and left eye (OS): 20/70. After surgery she developed large RPE hyperplasia and presented hand movement that did not improve with pinhole. Case 2: A 69-years-old female patient who had ERM in her OS with BCVA of 20/30 in both eyes (OU). PPV was assisted with brilliant blue (BB) to better visualize the ILM. During follow-up visits we evidenced RPE atrophy in the zone where peeling was done. In the last control after 2-years, her visual acuity was 20/40 that did not improve with pinhole. Discussion: There are three possible mechanisms to explain this complication: toxic damage, mechanical trauma during the membrane removal with forceps, or a combination of both. In our cases, a combination of them is probably the cause of the presence of RPE atrophy. Conclusion: Vitrectomy with membrane removal is successful in most cases with low rate of complications. Because RPE atrophy is infrequent, our suggestion is to continue performing this technique and if possible, it should be done without dye staining to minimize risks. Abbreviations: ERM = epiretinal membrane, ILM = internal limiting membrane, MH = macular hole, RPE = Retinal pigment epithelium, OD = right eye, BCVA = Best corrected visual acuity, OS = left eye, OU = both eyes, IOL = intraocular lens, OCT = Optical coherence tomography, BB = Brilliant blue, TB = Trypan blue, ICG = indocyanine green.


Assuntos
Membrana Epirretiniana , Perfurações Retinianas , Idoso , Atrofia , Membrana Basal/cirurgia , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Feminino , Humanos , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Perfurações Retinianas/cirurgia , Epitélio Pigmentado da Retina , Estudos Retrospectivos , Tomografia de Coerência Óptica , Vitrectomia/efeitos adversos , Vitrectomia/métodos
10.
Front Immunol ; 13: 866167, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35603187

RESUMO

Pathological correlates of potential autoimmune gastritis (AIG), defined by anti-parietal cell antibody (PCA) positivity in the absence of gastric atrophy, have never been described. We herein aimed to assess intraepithelial lymphocyte (IEL) infiltration in gastric corpus of AIG patients. From 2000 to 2021, among 53 potential AIG patients, we focused on nine (median age 61 years, IQR 53-82; four females) who subsequently developed overt AIG. IEL infiltration of the oxyntic mucosa was assessed before and after developing overt AIG by measuring deep and superficial CD3+ IEL. AIG patients with different degrees of corpus atrophy, healthy controls (HC), active H. pylori gastritis, celiac disease (CD), and Hashimoto's thyroiditis patients were included as controls. Of note, deep, but not superficial, CD3+ IEL count was higher (p<0.001) in potential AIG compared to HC and H. pylori gastritis. Deep CD3+ IEL infiltration did not change before or after the evolution into atrophy (median 9.6, IQR 8.8-12.4, vs 11.3, IQR 9.4-12.9). No difference was found in deep CD3+ IEL infiltration among potential, mild, and severe AIG, and compared to Hashimoto's thyroiditis or CD. A deep CD3+ IEL cut-off of >7/100 epithelial cells allowed discrimination of any AIG stage and severity (AUC=0.842). We conclude that an increased deep CD3+ IEL infiltration of the oxyntic mucosa could represent a marker of potential AIG. Prospective studies including a larger number of potential AIG patients are needed.


Assuntos
Doenças Autoimunes , Doença Celíaca , Gastrite , Doença de Hashimoto , Linfócitos Intraepiteliais , Atrofia , Doença Celíaca/patologia , Feminino , Mucosa Gástrica , Doença de Hashimoto/patologia , Humanos , Linfócitos Intraepiteliais/patologia , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Alzheimers Res Ther ; 14(1): 62, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505442

RESUMO

IMPORTANCE: The entry of artificial intelligence into medicine is pending. Several methods have been used for the predictions of structured neuroimaging data, yet nobody compared them in this context. OBJECTIVE: Multi-class prediction is key for building computational aid systems for differential diagnosis. We compared support vector machine, random forest, gradient boosting, and deep feed-forward neural networks for the classification of different neurodegenerative syndromes based on structural magnetic resonance imaging. DESIGN, SETTING, AND PARTICIPANTS: Atlas-based volumetry was performed on multi-centric T1-weighted MRI data from 940 subjects, i.e., 124 healthy controls and 816 patients with ten different neurodegenerative diseases, leading to a multi-diagnostic multi-class classification task with eleven different classes. INTERVENTIONS: N.A. MAIN OUTCOMES AND MEASURES: Cohen's kappa, accuracy, and F1-score to assess model performance. RESULTS: Overall, the neural network produced both the best performance measures and the most robust results. The smaller classes however were better classified by either the ensemble learning methods or the support vector machine, while performance measures for small classes were comparatively low, as expected. Diseases with regionally specific and pronounced atrophy patterns were generally better classified than diseases with widespread and rather weak atrophy. CONCLUSIONS AND RELEVANCE: Our study furthermore underlines the necessity of larger data sets but also calls for a careful consideration of different machine learning methods that can handle the type of data and the classification task best.


Assuntos
Inteligência Artificial , Aprendizado de Máquina , Algoritmos , Atrofia , Humanos , Síndrome
12.
Physiol Rep ; 10(8): e15281, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35439362

RESUMO

Mitochondria in the skeletal muscle are essential for maintaining metabolic plasticity and function. Mitochondrial quality control encompasses the dynamics of the biogenesis and remodeling of mitochondria, characterized by the constant fission and fusion of mitochondria in response to metabolic stressors. However, the roles of mitochondrial fission or fusion in muscle hypertrophy and atrophy remain unclear. The aim of this study was to determine whether mitochondrial fusion and fission events are influenced by muscle hypertrophy or atrophy stimulation. Twenty-six male F344 rats were randomly assigned to a control group or were subjected to up to 14 days of either plantaris overload (via tenotomy of the gastrocnemius and soleus muscles; hypertrophy group) or hindlimb cast immobilization (atrophy group). After 14 days of treatment, plantaris muscle samples were collected to determine the expression levels of mitochondrial fusion- and fission-related proteins. Muscle weight and total muscle protein content increased following plantaris overload in the hypertrophy group, but decreased following immobilization for 14 days in the atrophy group. In the hypertrophied muscle, the level of activated dynamin-related protein 1 (Drp1), phosphorylated at Ser616, significantly increased by 25.8% (p = 0.014). Moreover, the protein expression level of mitochondrial fission factor significantly decreased by 36.5% in the hypertrophy group compared with that of the control group (p = 0.017). In contrast, total Drp1 level significantly decreased in the atrophied plantaris muscle (p = 0.011). Our data suggest that mitochondrial fission events may be influenced by both muscle hypertrophy and atrophy stimulation, and that mitochondrial fission- related protein Drp1 plays an important role in the regulation of skeletal muscle in response to mechanical stimulation.


Assuntos
Dinâmica Mitocondrial , Músculo Esquelético , Animais , Atrofia , Hipertrofia/metabolismo , Masculino , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/metabolismo , Ratos , Ratos Endogâmicos F344
13.
F1000Res ; 11: 114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242306

RESUMO

Introduction: Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods: In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE<27 (n=14) and a normal cognition (NC) group with adjMMSE≥27 (n=20). A multiparametric approach, comprising structural magnetic resonance imaging measurement of different hippocampal segments and blood mRNA expression of redox and inflammatory genes was applied. Results: Our findings indicate that hippocampal segment volumes correlate positively with adjMMSE and negatively with the blood transcript levels of 19 genes, mostly redox genes correlating especially with the left subiculum and presubiculum. A strong negative correlation between hippocampal subfields atrophy and Sulfiredoxin-1 ( SRXN1) redox gene was emphasized. Conclusions: Concluding, these results suggest that SRXN1 might be a valuable candidate blood biomarker for non-invasively monitoring the evolution of hippocampal atrophy in CD patients.


Assuntos
Disfunção Cognitiva , Doenças Neurodegenerativas , Atrofia/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Estudos Transversais , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , RNA Mensageiro/genética
14.
Front Immunol ; 13: 843086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371081

RESUMO

Celiac Disease (CeD) is a complex immune disorder involving villous atrophy in the small intestine that is triggered by gluten intake. Current CeD diagnosis is based on late-stage pathophysiological parameters such as detection of specific antibodies in blood and histochemical detection of villus atrophy and lymphocyte infiltration in intestinal biopsies. To date, no early onset biomarkers are available that would help prevent widespread villous atrophy and severe symptoms and co-morbidities. To search for novel CeD biomarkers, we used single-cell RNA sequencing (scRNAseq) to investigate PBMC samples from 11 children before and after seroconversion for CeD and 10 control individuals matched for age, sex and HLA-genotype. We generated scRNAseq profiles of 9559 cells and identified the expected major cellular lineages. Cell proportions remained stable across the different timepoints and health conditions, but we observed differences in gene expression profiles in specific cell types when comparing patient samples before and after disease development and comparing patients with controls. Based on the time when transcripts were differentially expressed, we could classify the deregulated genes as biomarkers for active CeD or as potential pre-diagnostic markers. Pathway analysis showed that active CeD biomarkers display a transcriptional profile associated with antigen activation in CD4+ T cells, whereas NK cells express a subset of biomarker genes even before CeD diagnosis. Intersection of biomarker genes with CeD-associated genetic risk loci pinpointed genetic factors that might play a role in CeD onset. Investigation of potential cellular interaction pathways of PBMC cell subpopulations highlighted the importance of TNF pathways in CeD. Altogether, our results pinpoint genes and pathways that are altered prior to and during CeD onset, thereby identifying novel potential biomarkers for CeD diagnosis in blood.


Assuntos
Doença Celíaca , Atrofia , Biomarcadores , Doença Celíaca/diagnóstico , Doença Celíaca/genética , Criança , Humanos , Leucócitos Mononucleares/metabolismo , Análise de Sequência de RNA , Soroconversão
16.
World J Gastroenterol ; 28(12): 1272-1283, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35431514

RESUMO

BACKGROUND: Research on celiac disease (CD) in northwest China is still in its infancy. At present, large-sample data on the epidemiological, clinical, and pathological characteristics of CD are limited. AIM: To investigate the epidemiological, clinical, and pathological characteristics of CD in northwest China. METHODS: The clinical data of 2884 patients with gastrointestinal (GI) symptoms were retrospectively analyzed. Total immunoglobulin A (IgA) and anti-tissue transglutaminase (tTG) IgA levels were examined in all patients. Gastroscopy and colonoscopy were performed in patients with positive anti-tTG IgA and deficient total IgA levels. Atrophy of the duodenal and ileal villi was examined and histopathological examinations were performed. The modified Marsh-Oberhuber classification system was used to grade villous atrophy in the duodenum or distal ileum. The patients' Helicobacter pylori (H. pylori) infection status was compared in terms of clinical presentation and Marsh grade. Statistical analyses were performed using the t-test or chi-square test. RESULTS: Among the 2884 patients, 73 were positive for serum anti-tTG IgA, and 50 were diagnosed with CD. The CD detection rate was significantly higher in Kazakhs (4.39%) than in Uyghurs (2.19%), Huis (0.71%), and Hans (0.55%). The main symptoms of CD were chronic diarrhea, anorexia, anemia, fatigue, weight loss, sleep disorders, osteopenia, and osteoporosis. The body mass index of patients with CD was significantly lower than that of patients without CD. A total of 69 patients with positive serum anti-tTG IgA and two patients with deficient total IgA levels underwent GI endoscopy. Endoscopy revealed crypt hyperplasia and/or duodenal villous atrophy, mainly manifested as nodular mucosal atrophy, grooves, and fissures. The difference in H. pylori infection rates was not statistically significant between CD and non-CD patients but was significantly different among CD patients with different Marsh grades. CONCLUSION: Among the patients with GI symptoms in northwestern China, the prevalence of CD was more in the Uyghur and Kazakh populations. H. pylori infection may be associated with CD severity.


Assuntos
Doença Celíaca , Infecções por Helicobacter , Atrofia/epidemiologia , Atrofia/patologia , Autoanticorpos , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Duodeno/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Humanos , Imunoglobulina A , Estudos Retrospectivos , Transglutaminases
17.
Neurosciences (Riyadh) ; 27(2): 111-115, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35477912

RESUMO

Kearns-Sayre Syndrome (KSS) is a subtype of chronic progressive external ophthalmoplegia (CPEO). In this case, A 21-year-old man diagnosed with KSS, and presented with chronic progressive blepharoptosis (ptosis) and external ophthalmoplegia, diffuse depigmentation of the retinal pigment epithelium, and cerebellar ataxia, with a cerebrospinal fluid protein of 254 mg/dL, was reported. Genetic screening revealed a novel mutated gene in SLC25A4 in the patient as well as in his mother: NM_001151:c.170G>C in exon 2. Its imaging finding is a characteristic progressive atrophy of the right cerebellar hemisphere. In conclusion, we found a case of KSS with a novel mutated gene in SLC25A4: NM_001151:c.170G>C in exon 2 as the pathogenic mechanism, and found that KSS can be caused only when the proportion of mutations in the SLC25A4 gene reach a certain degree, and the patient with KSS showed a unique cranial imaging feature of unilateral progressive cerebellar atrophy.


Assuntos
Síndrome de Kearns-Sayre , Oftalmoplegia Externa Progressiva Crônica , Translocador 1 do Nucleotídeo Adenina/genética , Adulto , Atrofia , Feminino , Humanos , Síndrome de Kearns-Sayre/diagnóstico por imagem , Síndrome de Kearns-Sayre/genética , Masculino , Mães , Mutação/genética , Oftalmoplegia Externa Progressiva Crônica/diagnóstico , Oftalmoplegia Externa Progressiva Crônica/genética , Adulto Jovem
18.
J Neurol Sci ; 437: 120269, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35483239

RESUMO

BACKGROUND: Retinal atrophy in the chronic phase of optic neuritis (ON) in anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear. METHODS: Patients with these diseases were repeatedly evaluated using optical coherence tomography (OCT) for the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) in the ON-involved eyes during relapse-free period after the first ON episode before relapse. Optic MRI with short tau inversion recovery (STIR) sequences was further evaluated retrospectively. RESULTS: Twelve patients with MOGAD (20 eyes with ON-involvement) and 14 with AQP4-Ab-positive NMOSD (16 eyes with ON-involvement) were enrolled. The progression of retinal atrophy ≥12 months after onset was observed in AQP4-Ab-positive NMOSD, but was not apparent in MOGAD. A decrease in retinal thickness by the same amount results in more severe visual impairment in AQP4-Ab-positive NMOSD. On optic MRI, the residual STIR hyperintensity in the optic nerves remained in the chronic phase in almost all eyes with ON in both diseases. Optic nerve atrophy occurred in all evaluated ON-involved eyes in AQP4-Ab-positive NMOSD, while it was observed in half of ON-involved eyes in MOGAD. CONCLUSIONS: Progression of retinal atrophy in the chronic phase has been observed in patients with AQP4-Ab-positive NMOSD, while it remains uncertain in patients with MOGAD. The visual impairments upon similar levels of retinal atrophy would be worse in AQP4-Ab-positive NMOSD, possibly attributable in part to a higher incidence of optic nerve atrophy in this disease.


Assuntos
Neuromielite Óptica , Neurite Óptica , Aquaporina 4 , Atrofia , Autoanticorpos , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica/complicações , Neuromielite Óptica/diagnóstico por imagem , Neurite Óptica/diagnóstico por imagem , Estudos Retrospectivos
19.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(2): 222-226, 2022 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-35435183

RESUMO

OBJECTIVE: To summarize and analyze the clinical characteristics of children with basal ganglia germinoma and to improve the level of early clinical diagnosis. METHODS: The clinical data of children diagnosed with basal ganglia germinoma admitted to the Pediatric Surgery Ward of Peking University First Hospital from January 2013 to December 2020 were retrospectively analyzed, and descriptive statistics were used to analyze the clinical characteristics of children with basal ganglia germinoma. RESULTS: A total of 30 patients were included in the study, 28 were male, 2 were female, the mean age at onset was (9.7±2.2) years, the median disease duration was 7 months, 27 had unilateral disease, and 3 had bilateral disease. The clinical manifestations were decreased limb muscle strength, cognitive function disorders, polydipsia, precocious puberty, intracranial hypertension, dysphonia and swallowing dysfunction. The serum and cerebrospinal fluid tumor marker alpha-fetoprotein (AFP) were normal in the 30 patients, and the serum and cerebrospinal fluid tumor marker ß-human chorionic gonadotropin (ß-HCG) were normal in 8 patients.The serum ß-HCG was normal in 11 patients but the cerebrospinal fluid ß-HCG was slightly elevated, and the serum and cerebrospinal fluid ß-HCG were slightly elevated in 11 patients. A total of 33 lesions with irregular shapes were found by imaging examination, including 15 (45.5%) patchy lesions, 10 (30.3%) patchy lesions, and 8 (24.2%) round-like high-density lesions. Tumors showed obvious high-density shadows on computed tomography (CT) scan. Magnetic resonance imaging (MRI) scan of the tumors showed low or isointensity on T1WI and isointensity on T2WI, accompanied by mild peritumoral edema, hemispheric atrophy, cerebral peduncle atrophy, calcification, cystic degeneration, ventricular dilatation and wallerian degeneration. On contrast-enhanced scans, the tumor showed no enhancement or heterogeneous enhancement. CONCLUSION: The main age of onset of germ cell tumors in the basal ganglia in children is about 10 years old, and males are absolutely dominant. The clinical features and imaging manifestations have certain characteristics. With both combined, the early diagnosis of germ cell tumors in the basal ganglia can be improved.


Assuntos
Neoplasias Encefálicas , Germinoma , Neoplasias Embrionárias de Células Germinativas , Atrofia/complicações , Atrofia/patologia , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Biomarcadores Tumorais , Neoplasias Encefálicas/diagnóstico por imagem , Criança , Gonadotropina Coriônica Humana Subunidade beta , Feminino , Germinoma/complicações , Germinoma/diagnóstico , Germinoma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos
20.
Genes (Basel) ; 13(4)2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35456509

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia worldwide and is characterized by a progressive decline in cognitive functions. Accumulation of amyloid-ß plaques and neurofibrillary tangles are a typical feature of AD neuropathological changes. The entorhinal cortex (EC) is the first brain area associated with pathologic changes in AD, even preceding atrophy of the hippocampus. In the current study, we have performed a meta-analysis of publicly available expression data sets of the entorhinal cortex (EC) in order to identify potential pathways underlying AD pathology. The meta-analysis identified 1915 differentially expressed genes (DEGs) between the EC from normal and AD patients. Among the downregulated DEGs, we found a significant enrichment of biological processes pertaining to the "neuronal system" (R-HSA-112316) and the "synaptic signaling" (GO:0099536), while the "regulation of protein catabolic process" (GO:00042176) and "transport of small molecules" (R-HSA-382551) resulted in enrichment among both the upregulated and downregulated DEGs. Finally, by means of an in silico pharmacology approach, we have prioritized drugs and molecules potentially able to revert the transcriptional changes associated with AD pathology. The drugs with a mostly anti-correlated signature were: efavirenz, an anti-retroviral drug; tacrolimus, a calcineurin inhibitor; and sirolimus, an mTOR inhibitor. Among the predicted drugs, those potentially able to cross the blood-brain barrier have also been identified. Overall, our study found a disease-specific set of dysfunctional biological pathways characterizing the EC in AD patients and identified a set of drugs that could in the future be exploited as potential therapeutic strategies. The approach used in the current study has some limitations, as it does not account for possible post-transcriptional events regulating the cellular phenotype, and also, much clinical information about the samples included in the meta-analysis was not available. However, despite these limitations, our study sets the basis for future investigations on the pathogenetic processes occurring in AD and proposes the repurposing of currently used drugs for the treatment of AD patients.


Assuntos
Doença de Alzheimer , Córtex Entorrinal , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides , Atrofia/patologia , Córtex Entorrinal/metabolismo , Córtex Entorrinal/patologia , Hipocampo/metabolismo , Humanos
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