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1.
J Cell Mol Med ; 28(5): e17979, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37795791

RESUMO

Bladder transitional cell carcinoma (BTCC) forms more than 90% of bladder cancer cases. It brings challenges to the early diagnosis and therapy of BTCC, due to lack of efficient screening biomarkers. We used weighted gene co-expression network analysis (WGCNA) combined competing endogenous RNA (ceRNA) network construction depending on TCGA datasets to investigate potential hub genes and regulatory pathways associated with occurrence and progression of BTCC. We further used real-time polymerase chain reaction (RT-PCR) to validate the relative expression genes correlated with BTCC. By WGCNA, the gene co-expression module with 11 genes was found corelated with BTCC tumour stage and prognosis after survival analyses. Ultimately, we put 100 highly stage-related genes into the above constructed ceRNA network and then constructed another new network. Among them, all elements in AC112721.1/LINC00473/AC128709.1-hsa-mir-195-RECK and LINC00460-hsa-mir-429-ZFPM2 axes were simultaneously corelated with overall survival. RT-PCR showed that AKAP12 was downregulated in tumour tissues. The hub genes screened out in the present study may provide ideals for further treatment on BTCC.

2.
Neurol Sci ; 42(6): 2337-2345, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33043395

RESUMO

AIMS: To detect abnormal eye movements in Parkinson's disease and explore its correlation with clinical characteristics and their value for diagnosis. METHODS: We recruited forty-nine Parkinson's disease patients, including 35 early Parkinson's disease patients (Hoehn-Yahr: 1 to 2 stage) and 14 advanced Parkinson's disease patients (Hoehn-Yahr: 3 to 5 stage) and 23 healthy controls. Clinical manifestations in Parkinson's disease patients were recorded. Oculomotor performances including fixation, gaze, saccade in horizontal and vertical direction, and smooth pursuit in horizontal and vertical direction were measured by video-oculography. RESULTS: We found that five oculomotor parameters, namely square wave jerk frequency, latency of downward saccade, latency of upward saccade, accuracy of upward saccade, and gain of horizontal smooth pursuit were significantly different in Parkinson's disease patients and controls. When combining all these five parameters, we got the diagnostic sensitivity of 78.3% and specificity of 95.2%. More deficits in upward saccade than in other directions were associated with disease duration and progression of Parkinson's disease. CONCLUSION: Our primary study suggests that oculomotor examination might serve as an aid in the clinical assessment of Parkinson's disease patients and differentiating between early Parkinson's disease and normal controls.


Assuntos
Transtornos da Motilidade Ocular , Doença de Parkinson , Movimentos Oculares , Humanos , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Acompanhamento Ocular Uniforme , Movimentos Sacádicos
3.
Development ; 144(8): 1368-1381, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28400433

RESUMO

Retinal degenerative diseases are the leading causes of blindness worldwide. Replacing lost retinal cells via stem cell-based therapies is an exciting, rapidly advancing area of translational research that has already entered the clinic. Here, we review the status of these clinical efforts for several significant retinal diseases, describe the challenges involved and discuss how basic developmental studies have contributed to and are needed to advance clinical goals.


Assuntos
Degeneração Retiniana/terapia , Transplante de Células-Tronco , Animais , Ensaios Clínicos como Assunto , Humanos , Modelos Biológicos , Retina/embriologia , Retina/patologia , Degeneração Retiniana/imunologia
4.
BMC Neurol ; 20(1): 145, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312236

RESUMO

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset, X-linked genetic, neurodegenerative disorder caused by a "premutation (PM)" in the fragile X mental retardation 1 (FMR1) gene. Here we report a case of FXTAS from mainland of China who presented with rare orthostatic tremor. A review of tremor of FXTAS in the literature is also included. CASE PRESENTATION: A 67-year-old right-handed farmer started with tremor of both legs 8 years ago which was present while standing but absent when sitting or lying and progressed with unsteady gait one and a half years ago. The brain MRI showed high intensity signal in the bilateral middle cerebellar peduncles (MCP) in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images and gene test for premutation for FMR1 was positive with 101 CGG repeats. The patient met the the diagnosis of definite FXTAS. Clonazepam and topiramate were administered to control tremor. We reviewed the literature and identified 64 cases with detailed clinical and genetic information. Orthostatic tremor associated with FXTAS is very rare. We found 85.2% patients reported tremor,42.6% with intention tremor,36.1% with kinetic tremor,32.8% with rest tremor and 29.5% with posture tremor. 37.7% of patients who have tremor showed at least two types of tremor. There were 6 patients with isolated rest tremor. There was 2 patient with voice tremor and 6 with head tremor. We also found that 74.6% FXTAS patients had family history of FMR1 gene associated diseases including Fragile X syndrome (FXS), FXTAS or fragile X-associated primary ovarian insufficiency (FXPOI). CONCLUSIONS: Adding our data to the available literature suggests that orthostatic tremor could be a rare initial manifestation of FXTAS and the review will increasing our understanding the phenotype of tremor in FXTAS. Family history of FMR1 gene associated diseases might be an important clue to the diagnosis.


Assuntos
Ataxia , Síndrome do Cromossomo X Frágil , Tremor , Idoso , Anticonvulsivantes/uso terapêutico , Ataxia/diagnóstico , Ataxia/tratamento farmacológico , Ataxia/genética , Ataxia/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Clonazepam/uso terapêutico , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/tratamento farmacológico , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Topiramato/uso terapêutico , Tremor/diagnóstico , Tremor/tratamento farmacológico , Tremor/genética , Tremor/fisiopatologia
5.
J Cell Physiol ; 234(11): 21395-21406, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31069793

RESUMO

To investigate the role of S100 calcium-binding protein A16 (S100A16) in hepatic lipid metabolism, S100a16 transgenic, S100a16 knockdown, and wildtype C57BL/6 mice were fed either a high-fat diet (HFD) or normal-fat diet (NFD) for 16 weeks. The results showed that for HFD-fed mice, S100a16 transgenic mice showed significantly more severe fatty liver than other HFD-fed mice, with a significant increase in serum triglyceride (TG) concentration, with more and larger lipid droplets in the liver, whereas S100a16 knockdown mice were completely opposite, with liver fat lesions and TG serological changes being the mildest; for NFD-fed mice, liver fat accumulation and serum TG concentrations were significantly lower than those fed HFD, and no significant lipid droplets were found in the liver. Further, we found that calmodulin (CaM) interacts with S100A16, a member of the AMP-activated protein kinase (AMPK) pathway. Our research found that S100A16 regulates the AMPK pathway-associated protein by interacting with CaM to regulate liver lipid synthesis. S100A16 regulates liver lipid metabolism through the CaM/CAMKK2/AMPK pathway. Overexpression of S100A16 promotes the deterioration of fatty liver induced by HFD, and low expression of S100A16 can attenuate fatty liver.


Assuntos
Hepatócitos/metabolismo , Lipogênese/fisiologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas S100/metabolismo , Animais , Dieta Hiperlipídica , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/fisiologia
7.
Am J Physiol Cell Physiol ; 312(2): C111-C118, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27881413

RESUMO

Stretch activation (SA) is a delayed increase in force that enables high power and efficiency from a cyclically contracting muscle. SA exists in various degrees in almost all muscle types. In Drosophila, the indirect flight muscle (IFM) displays exceptionally high SA force production (FSA), whereas the jump muscle produces only minimal FSA We previously found that expressing an embryonic (EMB) myosin heavy chain (MHC) isoform in the jump muscle transforms it into a moderately SA muscle type and enables positive cyclical power generation. To investigate whether variation in MHC isoforms is sufficient to produce even higher FSA, we substituted the IFM MHC isoform (IFI) into the jump muscle. Surprisingly, we found that IFI only caused a 1.7-fold increase in FSA, less than half the increase previously observed with EMB, and only at a high Pi concentration, 16 mM. This IFI-induced FSA is much less than what occurs in IFM, relative to isometric tension, and did not enable positive cyclical power generation by the jump muscle. Both isometric tension and FSA of control fibers decreased with increasing Pi concentration. However, for IFI-expressing fibers, only isometric tension decreased. The rate of FSA generation was ~1.5-fold faster for IFI fibers than control fibers, and both rates were Pi dependent. We conclude that MHC isoforms can alter FSA and hence cyclical power generation but that isoforms can only endow a muscle type with moderate FSA Highly SA muscle types, such as IFM, likely use a different or additional mechanism.


Assuntos
Drosophila/fisiologia , Voo Animal/fisiologia , Contração Isométrica/fisiologia , Músculo Esquelético/fisiologia , Cadeias Pesadas de Miosina/metabolismo , Reflexo de Estiramento/fisiologia , Animais , Cadeias Pesadas de Miosina/química , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo
8.
Am J Physiol Cell Physiol ; 313(6): C621-C631, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28835434

RESUMO

Muscle stretch activation (SA) is critical for optimal cardiac and insect indirect flight muscle (IFM) power generation. The SA mechanism has been investigated for decades with many theories proposed, but none proven. One reason for the slow progress could be that multiple SA mechanisms may have evolved in multiple species or muscle types. Laboratories studying IFM SA in the same or different species have reported differing SA functional properties which would, if true, suggest divergent mechanisms. However, these conflicting results might be due to different experimental methodologies. Thus, we directly compared SA characteristics of IFMs from two SA model systems, Drosophila and Lethocerus, using two different fiber bathing solutions. Compared with Drosophila IFM, Lethocerus IFM isometric tension is 10- or 17-fold higher and SA tension was 5- or 10-fold higher, depending on the bathing solution. However, the rate of SA tension generation was 9-fold faster for Drosophila IFM. The inverse differences between rate and tension in the two species causes maximum power output to be similar, where Drosophila power is optimized in the bathing solution that favors faster muscle kinetics and Lethocerus in the solution that favors greater tension generation. We found that isometric tension and SA tension increased with calcium concentration for both species in both solutions, reaching a maximum plateau around pCa 5.0. Our results favor a similar mechanism for both species, perhaps involving a troponin complex that does not fully calcium activate the thin filament thus leaving room for further tension generation by SA.


Assuntos
Cálcio/metabolismo , Drosophila/fisiologia , Voo Animal/fisiologia , Heterópteros/fisiologia , Contração Muscular/fisiologia , Tono Muscular/fisiologia , Animais , Músculos/fisiologia , Sarcômeros
9.
World Neurosurg ; 184: e518-e523, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38316178

RESUMO

OBJECTIVE: Social support can be divided into emotional support, tool support, and information support in function or mode. Emotional support is an encouragement, expressed as love and care, respect and value, encouragement and compassion, and psychological resilience due to adaptation to adversity and stressors, which is conducive to personal positive psychological adjustment and good functional status. This study aims to explore the status of resilience and social support in elderly stroke patients and examine the correlation between the 2 factors. METHODS: Convenience sampling was used to survey 280 elderly stroke ischemic patients admitted to the Department of Neurology in our hospital from January to December 2020. General information, resilience, and social support were assessed through questionnaires. RESULTS: The participants had a moderate level of resilience, with an average score of 63.77 ± 9.99. The total social support score ranged with an average score of 33.72 ± 5.77, indicating a relatively low level of social support. After the Pearson correlation analysis, there was a positive correlation between resilience and social support, namely, r = 0.277, P < 0.05. CONCLUSIONS: Enhancing social support among elderly stroke patients is an effective way to improve their psychological resilience.


Assuntos
AVC Isquêmico , Resiliência Psicológica , Acidente Vascular Cerebral , Humanos , Idoso , Apoio Social , Adaptação Psicológica , Inquéritos e Questionários
10.
Biophys J ; 104(12): 2662-70, 2013 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-23790374

RESUMO

The mechanism behind stretch activation (SA), a mechanical property that increases muscle force and oscillatory power generation, is not known. We used Drosophila transgenic techniques and our new muscle preparation, the jump muscle, to determine if myosin heavy chain isoforms influence the magnitude and rate of SA force generation. We found that Drosophila jump muscles show very low SA force and cannot produce positive power under oscillatory conditions at pCa 5.0. However, we transformed the jump muscle to be moderately stretch-activatable by replacing its myosin isoform with an embryonic isoform (EMB). Expressing EMB, jump muscle SA force increased by 163% and it generated net positive power. The rate of SA force development decreased by 58% with EMB expression. Power generation is Pi dependent as >4 mM Pi was required for positive power from EMB. Pi increased EMB SA force, but not wild-type SA force. Our data suggest that when muscle expressing EMB is stretched, EMB is more easily driven backward to a weakly bound state than wild-type jump muscle. This increases the number of myosin heads available to rapidly bind to actin and contribute to SA force generation. We conclude that myosin heavy chain isoforms influence both SA kinetics and SA force, which can determine if a muscle is capable of generating oscillatory power at a fixed calcium concentration.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Contração Isométrica , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Animais , Drosophila/metabolismo , Músculo Esquelético/fisiologia , Isoformas de Proteínas/metabolismo
11.
Neurochem Res ; 2013 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-24078266

RESUMO

Alzheimer's disease (AD) is characterized by Amyloid-ß (Aß) deposition in senile plaques in specific areas of the brain and by intraneuronal p-tau accumulation in neurofibrillary tangles. Cumulative evidence supports that oxidative stress is an important factor in the pathogenesis of AD and contributes to Aß generation. However, there is no effective treatment for AD. Human umbilical cord mesenchymal stem cells (HUMSCs) have potential therapeutic value for the treatment of neurological disease. However, the therapeutic impact of systemic administration of HUMSCs and their mechanism of action in AD have not yet been determined. Here, we found that intravenous infusion of HUMSCs significantly improved spatial learning and alleviated memory decline in an AßPP/PS1 mouse model of AD. HUMSC treatment also increased glutathione (GSH) activity and ratio of GSH to oxidative glutathione as well as superoxide dismutase activity, while decreasing malondialdehyde activity and protein carbonyl level, which suggests that HUMSC infusion alleviated oxidative stress in AßPP/PS1 mice. In addition, HUMSC infusion reduced ß-secretase 1 and CTFß, thus reducing Aß deposition in mice. HUMSCs may have beneficial effects in the prevention and treatment of AD.

12.
Can J Neurol Sci ; 40(5): 691-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23968943

RESUMO

BACKGROUND: Polymorphisms of genes participating in iron transportation have been associated with Alzheimer's disease (AD) risk. The association between transferrin (TF) gene rs1049296 (P570S) polymorphism and AD is controversial. METHODS: We performed meta analysis on data from 19 studies with 6310 cases and 13661 controls to reexamine the association between the TF gene rs1049296 polymorphism and AD. We applied a fixed-effects model to combine the odds ratio (OR) and 95% confidence intervals (95% CI). Egger's test was carried out to evaluate the potential publication bias. RESULTS: The overall ORs with 95% CIs showed statistical association between the TF gene rs1049296 polymorphism and the risk of AD in the allele contrast, the recessive model and the dominant model for allele C2 (fixed-effects pooled OR 1.11; 95% CI 1.05 to 1.17, pooled OR 1.13; 95% CI 1.06 to 1.21, and pooled OR 1.23; 95% CI 1.03 to 1.47, respectively). In the contrast of C2C2+C2C1 vs C1C1, large heterogeneity among the Asian subgroup (p=0.041, I2= 68.6%) was observed but not among the overall population (p = 0.184, I2= 22.4%). No publication bias was observed. CONCLUSIONS: The present meta analysis demonstrated that TF gene rs1049296 polymorphism is a genetic determinant of AD.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Transferrina/genética , Idoso , Idoso de 80 Anos ou mais , Viés , Bases de Dados Bibliográficas/estatística & dados numéricos , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Risco
13.
Zhonghua Yi Xue Za Zhi ; 93(29): 2324-8, 2013 Aug 06.
Artigo em Zh | MEDLINE | ID: mdl-24300157

RESUMO

OBJECTIVE: To explore the effect and mechanism of murine marrow stromal cells (MSCs) within cerebrospinal fluid (CSF) on Cu/Zn superoxide dismutase 1 (SOD1) transgenic mice. METHODS: A dose of 5×10(5) MSCs was injected into the CSF of SOD1 transgenic mice at the ages of 8, 10 and 12 weeks.Hanging wire test and motor neuron counts were used to assess disease progression of SOD1 mice. To examine the glial activation in murine lumbar spinal cord at 15 weeks of age, the sections were stained with antibody to CD11b and GFAP through immunohistochemistry.In vitro, mRNA expression of neurotrophin of MSCs was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with vehicle-treated mice, intrathecally transplanted MSCs enhanced motor performance and decreased motor neuron loss. An intrathecal injection of MSCs inhibited microglial (52 ± 7 vs 38 ± 7; F = 69.3, P = 0.02) and astrocyte (79 ± 9 vs 63 ± 9; F = 40.7, P = 0.03) activity in lumbar spinal cord at the age of 15 weeks of age. MSCs cultured in an inflammatory environment expressed a higher mRNA level of neurotrophin (P < 0.05). CONCLUSION: A CSF administration of MSCs has therapeutic effects on SOD1 mice. And the meditation of MSCs may be achieved through inhibiting neuroinflammation and secreting a variety of trophic factors.


Assuntos
Esclerose Lateral Amiotrófica/terapia , Transplante de Medula Óssea , Células Estromais/transplante , Animais , Astrócitos/metabolismo , Células da Medula Óssea/citologia , Células Cultivadas , Injeções Espinhais , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Neurônios Motores/metabolismo , Fatores de Crescimento Neural/metabolismo , Células Estromais/citologia , Superóxido Dismutase/genética , Superóxido Dismutase-1
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(4): 1085-1092, 2023 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37551481

RESUMO

OBJECTIVE: To explore the biological function of LINC00174 in multiple myeloma (MM). METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of LINC00174 and miR-150 in peripheral blood of MM patients and MM cell lines. EdU staining and flow cytometry were used to detect the effects of LINC00174 and miR-150 on the proliferation and apoptosis of MM cells. Western blot was used to detect the expressions of proliferation marker nuclear-related antigen Ki67, apoptosis-related protein cleaved caspase-3 and transcription factor forkhead box protein P1 (FOXP1). Bioinformatics and dual-luciferase reporter assay were used to verify the targeting relationship between LINC00174 and miR-150 and the targeting relationship between miR-150 and FOXP1. RESULTS: The level of LINC00174 was significantly increased in peripheral blood of MM patients and MM cell lines (P <0.05). Compared with NC-siRNA group, the expression of LINC00174 was significantly reduced in LINC00174-siRNA group, the proliferation of U266 cells was reduced, the apoptosis rate was significantly increased, the level of Ki67 protein was reduced, and the level of cleaved caspase-3 protein was increased (all P <0.05). LINC00174 targeted regulation of the expression of miR-150. Compared with LINC00174-siRNA+NC inhibitor group, the expression of miR-150 in U266 cells in LINC00174-siRNA+miR-150 inhibitor group was significantly reduced, the cell proliferation was enhanced, the apoptosis rate was reduced, the level of Ki67 protein was increased, and the level of cleaved caspase-3 was decreased (all P <0.05). FOXP1 is the target gene of miR-150. Compared with NC mimic group, the expression of FOXP1 protein in miR-150 mimic group was significantly reduced, the cell proliferation was reduced, the apoptosis rate was significantly increased, Ki67 protein level was decreased, and the level of cleaved caspase-3 was increased. Compared with miR-150 mimic + vector group, the expression of FOXP1 protein in miR-150 mimic + pcDNA-FOXP1 group was significantly increased, the cell proliferation was enhanced, the apoptosis rate was reduced, the level of Ki67 protein was increased, and the level of cleaved caspase-3 was decreased (all P <0.05). CONCLUSION: LINC00174 promotes the proliferation of MM cells and inhibits cell apoptosis by regulating the miR-150/ FOXP1 axis.


Assuntos
MicroRNAs , Mieloma Múltiplo , RNA Longo não Codificante , Humanos , Apoptose , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição Forkhead , Antígeno Ki-67 , MicroRNAs/genética , Mieloma Múltiplo/patologia , Proteínas Repressoras , RNA Interferente Pequeno , RNA Longo não Codificante/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-36981821

RESUMO

The comprehensive reform of agricultural water prices is an important policy for promoting the high-quality sustainable development of agriculture and ensuring national water security. In this study, based on farmer survey data from different water price policy implementation areas in the oasis-desert transition zone of the Heihe River Basin (HRB), crops are divided into high-water-consuming crops and low-water-consuming crops based on the average water consumption per hm2. The content of this study consists of two main parts: first, the study explores the response of farmers to different agricultural water price policies by comparing the impact of uniform water price and tiered water price policies on their planting structure. Second, it studies the areas where the tiered water price policy is implemented to verify the impact of price signals on farmers' production decisions. The results show that, compared with the uniform water price policy, the implementation of the tiered water price policy will significantly reduce the proportion of high-water-consuming crops planted when other conditions remain unchanged. Under the tiered water price policy, the increase in water prices will reduce the proportion of farmers planting high-water-consuming crops, but the difference is not significant. This result reveals that when the opportunity cost of irrigation water increases, farmers will increase the proportion of low-water-consuming crops. The findings also indicate that a higher educational level, improved land inflow, the number of crop types, and satisfaction with the current subsidy policy will help increase the proportion of low-water-consuming crops. However, an increase in the family-cultivated land area will reduce the area of low-water-consuming crops.


Assuntos
Fazendeiros , Rios , Humanos , Água , Agricultura/métodos , Produtos Agrícolas , China
16.
Lymphat Res Biol ; 21(6): 536-548, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37267206

RESUMO

Background: Lymphedema is a significant postsurgical complication observed in the majority of breast cancer patients. These multifactorial etiopathogenesis have a significant role in the development of novel diagnostic/prognostic biomarkers and the development of novel therapies. This review aims to ascertain the epigenetic alterations that lead to breast cancer-related lymphedema (BCRL), multiple pathobiological events, and the underlying genetic predisposing factors, signaling cascades pertinent to the lapses in effective prognosis/diagnosis, and finally to develop a suitable therapeutic regimen. Methods and Results: We have performed a literature search in public databases such as PubMed, Medline, Google Scholar, National Library of Medicine and screened several published reports. Search words such as epigenetics to induce BCRL, prognosis/diagnosis, primary lymphedema, secondary lymphedema, genetic predisposing factors for BRCL, conventional therapies, and surgery were used in these databases. This review described several epigenetic-based predisposing factors and the pathophysiological consequences of BCRL, which affect the overall quality of life, and the interplay of these events could foster the progression of lymphedema in breast cancer survivors. Prognosis/diagnostic and therapy lapses for treating BCRL are highly challenging due to genetic and anatomical variations, alteration in the lymphatic vessel contractions, and variable expression of several factors such as vascular endothelial growth factor (VEGF)-E and vascular endothelial growth factor receptor (VEGFR) in breast cancer survivors. Conclusion: We compared the efficacy of various conventional therapies for treating BCRL as a multidisciplinary approach. Further substantial research is required to decipher underlying signaling epigenetic pathways to develop chromatin-modifying therapies pertinent to the multiple etiopathogenesis to explore the correlation between the disease pathophysiology and novel therapeutic modalities to treat BCRL.


Assuntos
Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Linfedema , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Qualidade de Vida , Fator A de Crescimento do Endotélio Vascular , Linfedema Relacionado a Câncer de Mama/diagnóstico , Linfedema Relacionado a Câncer de Mama/genética , Linfedema Relacionado a Câncer de Mama/terapia , Linfedema/etiologia , Linfedema/genética
17.
J Exp Med ; 220(12)2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-37728563

RESUMO

Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.


Assuntos
Perfilação da Expressão Gênica , Neurônios , Animais , Ratos , Biomarcadores , Células Epiteliais , Pigmentos da Retina
18.
Medicine (Baltimore) ; 101(36): e30519, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086692

RESUMO

BACKGROUND: We report a case of a pregnant woman who presented posterior reversible encephalopathy syndrome (PRES) without pre-eclampsia, eclampsia, or any other common causes of PRES. METHODS: A 32-year-old primigravida at 25 weeks and 4 days of gestation was admitted to neurology department because of suffering intermittent headache, hearing loss, memory loss with mental and behavioral disorder, and blurred vision for 1 month. She was healthy before without hypertension, migraine, or other medical or family history. Brain magnetic resonance imaging (MRI) revealed diffuse symmetrical high-signal intensity lesions in the white matter, medulla oblongata, without enhancement. After completely multidisciplinary discussion and with the family of the patient, she accepted termination of pregnancy. RESULTS: After the operation, the patient improved symptomatically. The follow-up MRI showed a decrease of the white matter lesion after 3 months and complete recovery at postoperative 6 months. The patient returned to work without any neurological sequelae. CONCLUSION: It might widen the cause spectrum of PRES that pregnancy itself without pre-eclampsia, eclampsia, or any other known risk factors could cause PRES. Pregnancy with acute or subacute leukoencephalopathy should be screened related causes and risk factors carefully. Hormonal fluctuations during the pregnancy might account for pregnancy-related PRES.


Assuntos
Eclampsia , Síndrome da Leucoencefalopatia Posterior , Pré-Eclâmpsia , Adulto , Encéfalo , Eclampsia/diagnóstico , Feminino , Humanos , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/etiologia , Pré-Eclâmpsia/diagnóstico , Gravidez , Gestantes
19.
Am J Med Sci ; 364(5): 631-637, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35718124

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) and osteoporosis are two age-associated diseases. Body mass index (BMI) is positively associated with osteoporosis or osteopenia in T2DM population. Bone mineral density does not necessarily reflect the alterations in bone microarchitecture. Our aims were to investigate the relationship between BMI and femoral neck strength in males with T2DM and normal range of bone mineral density (BMD). METHODS: This study enrolled 115 males (median age 53.3 years) with T2DM and normal BMD. Femoral neck strength indexes, including compression strength index (CSI), bending strength index (BSI), impact strength index (ISI), were calculated by parameters generated from Dual-energy X-ray absorptiometry software. Pearson correlation analysis was performed to evaluate the relationships between BMI and femoral neck strength variables. RESULTS: Compared with T2DM-normal weight group, T2DM-overweight group and T2DM-obesity group had a higher femur neck and total femur BMDs. Cross sectional moment of inertia (CSMI), cross sectional area (CSA), section modulus (SM) were significantly higher (all p<0.05), and buckling ratio (BR) (6.35±2.08 vs 7.18±1.71) was lower in T2DM-obesity group than in T2DM-normal weight group. Compared with T2DM-normal weight group, CSI (all p<0.001), BSI (all p<0.001), ISI (all p<0.001) were significantly reduced in T2DM-obesity and T2DM-overweight groups. Pearson correlation analysis indicated that BMI was negatively correlated with CSI (r= - 0.457, p<0.001), BSI(r = -0.397, p<0.001), ISI (r = - 0.414, p<0.001). CONCLUSIONS: Higher BMI is associated with lower femoral neck strength in males with T2DM and normal BMD. It implies that femoral neck fracture risk increases in obese and diabetic males, despite their high bone density.


Assuntos
Diabetes Mellitus Tipo 2 , Osteoporose , Humanos , Masculino , Pessoa de Meia-Idade , Colo do Fêmur/diagnóstico por imagem , Densidade Óssea , Índice de Massa Corporal , Sobrepeso , Absorciometria de Fóton , Obesidade , Osteoporose/etiologia
20.
Front Hum Neurosci ; 16: 806122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35982687

RESUMO

Background and purpose: We previously established a radiological protocol to discriminate multiple system atrophy-parkinsonian subtype (MSA-P) from Parkinson's disease (PD). However, we do not know if it can differentiate early stage disease. This study aimed to investigate whether the morphological and intensity changes in susceptibility weighted imaging (SWI) of the lentiform nucleus (LN) could discriminate MSA-P from PD at early stages. Methods: We retrospectively enrolled patients with MSA-P, PD and sex- and age-matched controls whose brain MRI included SWI, between January 2015 and July 2020 at the Movement Disorder Center. Two specialists at the center reviewed the medical records and made the final diagnosis, and two experienced neuroradiologists performed MRI analysis, based on a defined and revised protocol for conducting morphological measurements of the LN and signal intensity. Results: Nineteen patients with MSA-P and 19 patients with PD, with less than 2 years of disease duration, and 19 control individuals were enrolled in this study. We found that patients with MSA- P presented significantly decreased size in the short line (SL) and corrected short line (cSL), ratio of the SL to the long line (SLLr) and corrected SLLr (cSLLr) of the LN, increased standard deviation of signal intensity (SIsd_LN, cSIsd_LN) compared to patients with PD and controls (P < 0.05). With receiver operating characteristic (ROC) analysis, this finding had a sensitivity of 89.5% and a specificity of 73.7% to distinguish MSA- P from PD. Conclusion: Compared to PD and controls, patients with MSA-P are characterized by a narrowing morphology of the posterior region of the LN. Quantitative morphological changes provide a reference for clinical auxiliary diagnosis.

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