Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biomacromolecules ; 21(3): 1202-1213, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-31895550

RESUMO

Regulating cell migration dynamics is of significance in tissue engineering and regenerative medicine. A 3D scaffold was created to provide various topographies based on a poly(ε-caprolactone) (PCL) self-induced nanohybrid shish-kebab structure, which consisted of aligned PCL nanofibers and spaced PCL crystal lamellae grown on the fibers. Electrospinning was applied followed by self-induced crystallization. The results resembled natural collagen fibrils in an extracellular matrix. This variable microstructure enabled control of cell adhesion and migration. The kebab size was controlled by initial PCL concentrations. The geometry of cells seeded on the fibers was less elongated, but the adhesion was more polarized with a higher nuclear shape index and faster migration speed. These results could aid in rapid endothelialization in tissue engineering.

2.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3558-3561, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602922

RESUMO

To preliminarily investigate the effect of Tripterygium Glycosides Tablets( TGT) combined with traditional Chinese medicine( TCM) on the fertility and female menstruation on persons who have took during childhood. The children with henoch-schonlein purpura( HSP) or henoch-schonlein purpura nephritis( HSPN) who treated with TGT under 18 years old and now older than 18 years old( including 18 years old) during January 1998 to December 2010 were selected in our research. The content of follow-up visit included marriage,marriage age,fertility and child health; and unmarried female patients were asked whether they had menstrual abnormalities. The data of the unmarried female patients,including age,clinical classification,TCM syndrome type,initial dose and other related factors that may affect menstrual cycle,was analyzed by using binary logistic regression analysis. A total of 195 patients who met the criteria were followed up in this study,and 26 patients married for more than 1 year. Among the 26 married patients,1 HSP patient had no birth planning due to rheumatoid arthritis,and the remaining 25 patients all had given birth or were pregnant. The 169 unmarried patients included 89 female patients. Among the 89 female patients,4 cases refused to tell the menstrual situations,72 cases had normal menstruation( 84. 7%),13 cases had abnormal menstruation( 15. 3%),and there was no case of amenorrhea. Logistic regression analysis results showed that the age,clinical classification,TCM syndrome type and initial dose had no correlation with abnormal menstruation. Our results demonstrated that TGT has no effect on adulthood fertility among patients who took TGT combined with traditional Chinese medicine during childhood.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Fertilidade/efeitos dos fármacos , Glicosídeos/farmacologia , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Tripterygium/química , Adolescente , Adulto , Criança , Feminino , Humanos , Medicina Tradicional Chinesa , Comprimidos
3.
Artigo em Inglês | MEDLINE | ID: mdl-31448270

RESUMO

Microbial cells in bioprocesses are usually described with averaged parameters. But in fact, single cells within populations vary greatly in characteristics such as stress resistance, especially in response to carbon source gradients. Our aim was to introduce tools to quantify population heterogeneity in bioprocesses using a combination of reporter strains, flow cytometry, and easily comprehensible parameters. We calculated mean, mode, peak width, and coefficient of variance to describe distribution characteristics and temporal shifts in fluorescence intensity. The skewness and the slope of cumulative distribution function plots illustrated differences in distribution shape. These parameters are person-independent and precise. We demonstrated this by quantifying growth-related population heterogeneity of Saccharomyces cerevisiae and Escherichia coli reporter strains in steady-state of aerobic glucose-limited chemostat cultures at different dilution rates and in response to glucose pulses. Generally, slow-growing cells showed stronger responses to glucose excess than fast-growing cells. Cell robustness, measured as membrane integrity after exposure to freeze-thaw treatment, of fast-growing cells was strongly affected in subpopulations of low membrane robustness. Glucose pulses protected subpopulations of fast-growing but not slower-growing yeast cells against membrane damage. Our parameters could successfully describe population heterogeneity, thereby revealing physiological characteristics that might have been overlooked during traditional averaged analysis.

4.
Trials ; 20(1): 538, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464626

RESUMO

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is the most common secondary glomerular disease in children. Currently, the treatment for HSPN is always selected based on the Kidney Disease Improving Global Outcomes guidelines; however, this approach may lead to undertreatment, especially in patients with persistent proteinuria that does not reach nephrotic levels and/or hematuria and those with a pathological classification between grades 1 and 3 according to the International Study of Kidney Disease in Children. This study was performed to evaluate the curative effect and safety of a traditional Chinese medicine (TCM) integrated treatment program in this type of HSPN. METHODS: This multicenter, open-label, large-sample, randomized controlled trial was performed in China and included 500 children with HSPN exhibiting mild pathological patterns. The treatment group to control group ratio was 2:1, and each group was further stratified into two types, light and heavy, according to urinary protein quantification and pathological type. The treatment group received tripterygium glycosides (TGs), tanshinone IIa sodium sulfonate injection, and Chinese herbs selected based on syndrome differentiation in TCM. The heavy and light subgroups received treatment courses and dosages of TG. In the control groups, the light group received benazepril hydrochloride tablets, low molecular weight heparin calcium injection, dipyridamole tablets, and a Chinese medicine placebo, while the heavy group received the same treatment plus prednisone. All groups were treated for 3 months and then followed up for 9 months. The efficacy and safety of the treatments were then evaluated among the groups. DISCUSSION: Currently, few treatments are available for HSPN patients with mild pathological patterns indicating light to moderate proteinuria and/or hematuresis. In this large-sample study, we provide a new approach for HSPN that includes an integrated treatment program that incorporates TCM. TRIAL REGISTRATION: Clinical Trials.gov, NCT03591471 . Re-registered on 19 July 2018.


Assuntos
/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , Nefrite/tratamento farmacológico , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Tripterygium , /efeitos adversos , Adolescente , Fatores Etários , Criança , Pré-Escolar , China , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Glicosídeos/efeitos adversos , Glicosídeos/isolamento & purificação , Humanos , Masculino , Estudos Multicêntricos como Assunto , Nefrite/diagnóstico , Púrpura de Schoenlein-Henoch/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento , Tripterygium/química
5.
Biochim Biophys Acta Mol Basis Dis ; 1865(10): 2694-2705, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31348989

RESUMO

Leber congenital amaurosis (LCA) is the most serious form of inherited retinal dystrophy that leads to blindness or severe visual impairment within a few months after birth. Approximately 1-2% of the reported cases are caused by mutations in the LCA5 gene. This gene encodes a ciliary protein called LCA5 that is localized to the connecting cilium of photoreceptors. The retinal phenotypes caused by LCA5 mutations and the underlying pathological mechanisms are still not well understood. In this study, we knocked out the lca5 gene in zebrafish using CRISPR/Cas9 technology. An early onset visual defect is detected by the ERG in 7 dpf lca5-/- zebrafish. Histological analysis by HE staining and immunofluorescence reveal progressive degeneration of rod and cone photoreceptors, with a pattern that cones are more severely affected than rods. In addition, ultrastructural analysis by transmission electron microscopy shows disordered and broken membrane discs in rods' and cones' outer segments, respectively. In our lca5-/- zebrafish, the red-cone opsin and cone α-transducin are selectively mislocalized to the inner segment and synaptic terminal. Moreover, we found that Ift88, a key component of the intraflagellar transport complex, is retained in the outer segments. These data suggest that the intraflagellar transport complex-mediated outer segment protein trafficking might be impaired due to lca5 deletion, which finally leads to a type of retinal degeneration mimicking the phenotype of cone-rod dystrophy in human. Our work provides a novel animal model to study the physiological function of LCA5 and develop potential treatments of LCA.

6.
Anal Chem ; 91(9): 5499-5503, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986341

RESUMO

We demonstrate a novel optomechanical synchronization method to achieve ultrahigh-contrast time-gated fluorescence imaging using live zebrafish as models. Silicon quantum dot nanoparticles (SiQDNPs) with photoluminescence lifetime of about 16 µs were used as the long-lived probes to enable background autofluorescence removal and multiplexing through time-gating. A continuous-wave 405 nm laser as the excitation source was focused on a rotating optical chopper on which the emission light beam obtained from an inverted fluorescence microscope was also focused but with a phase difference such that in a short delay after the excitation laser is blocked, the emission light beam passes through the optical chopper, initiating the image acquisition by a conventional sensor. Both excitation and detection time windows were synchronized by one optical chopper, eliminating the need for pulsed light source and image intensifier which is often used as ultrafast optical shutter. Through use of the cost-effective time-gating method, nearly all background autofluorescence emitted from the yolk sac of a zebrafish embryo microinjected with the SiQDNPs was removed, leading to a 45-fold increase in signal-to-background ratio. Furthermore, two kinds of fluorescence signals emitted from the microinjected SiQDNPs and the intrinsic green fluorescent protein of transgenic zebrafish larvae can be clearly separated through time-gating.

7.
Biochim Biophys Acta Mol Basis Dis ; 1865(6): 1273-1283, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30684641

RESUMO

Mutations in the photoreceptor cell-specific nuclear receptor gene Nr2e3 increased the number of S-cone photoreceptors in human and murine retinas and led to retinal degeneration that involved photoreceptor and non-photoreceptor cells. The mechanisms underlying these complex phenotypes remain unclear. In the hope of understanding the precise role of Nr2e3 in photoreceptor cell fate determination and differentiation, we generated a line of Nr2e3 knockout zebrafish using CRISPR technology. In these Nr2e3-null animals, rod precursors undergo terminal mitoses but fail to differentiate as rods. Rod-specific genes are not expressed and the outer segment (OS) fails to form. Formation and differentiation of cone photoreceptors is normal. Specifically, there is no increase in the number of UV-cone or S-cone photoreceptors. Laminated retinal structure is maintained. After normal development, L-/M-cones selectively degenerate, with progressive shortening of OS that starts at age 1 month. The amount of cone phototransduction proteins is concomitantly reduced, whereas UV- and S-cones have normal OS lengths even at age 10 months. In vitro studies show Nr2e3 synergizes with Crx and Nrl to enhance rhodopsin gene expression. Nr2e3 does not affect cone opsin expression. Our results extend the knowledge of Nr2e3's roles and have specific implications for the interpretation of the phenotypes observed in human and murine retinas. Furthermore, our model may offer new opportunities in finding treatments for enhanced S-cone syndrome (ESCS) and other retinal degenerative diseases.


Assuntos
Diferenciação Celular/genética , Mutação , Receptores Citoplasmáticos e Nucleares/genética , Células Fotorreceptoras Retinianas Cones/patologia , Degeneração Retiniana/genética , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Proteínas de Peixe-Zebra/genética , Animais , Sequência de Bases , Sistemas CRISPR-Cas , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Microscopia Eletrônica de Transmissão , Receptores Citoplasmáticos e Nucleares/metabolismo , Retina/embriologia , Retina/crescimento & desenvolvimento , Retina/ultraestrutura , Células Fotorreceptoras Retinianas Cones/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Células Fotorreceptoras Retinianas Bastonetes/citologia , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
8.
Autophagy ; 15(3): 453-465, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30205735

RESUMO

Macroautophagy/autophagy is an important intracellular mechanism for the maintenance of cellular homeostasis. Here we show that the CERKL (ceramide kinase like) gene, a retinal degeneration (RD) pathogenic gene, plays a critical role in regulating autophagy by stabilizing SIRT1. In vitro and in vivo, suppressing CERKL results in impaired autophagy. SIRT1 is one of the main regulators of acetylation/deacetylation in autophagy. In CERKL-depleted retinas and cells, SIRT1 is downregulated. ATG5 and ATG7, 2 essential components of autophagy, show a higher degree of acetylation in CERKL-depleted cells. Overexpression of SIRT1 rescues autophagy in CERKL-depleted cells, whereas CERKL loses its function of regulating autophagy in SIRT1-depleted cells, and overexpression of CERKL upregulates SIRT1. Finally, we show that CERKL directly interacts with SIRT1, and may regulate its phosphorylation at Ser27 to stabilize SIRT1. These results show that CERKL is an important regulator of autophagy and it plays this role by stabilizing the deacetylase SIRT1.

9.
Blood ; 133(8): 805-815, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30482793

RESUMO

Hematopoietic stem and progenitor cells (HSPCs) originate from the hemogenic endothelium via the endothelial-to-hematopoietic transition, are self-renewing, and replenish all lineages of blood cells throughout life. BCAS2 (breast carcinoma amplified sequence 2) is a component of the spliceosome and is involved in multiple biological processes. However, its role in hematopoiesis remains unknown. We established a bcas2 knockout zebrafish model by using transcription activator-like effector nucleases. The bcas2 -/- zebrafish showed severe impairment of HSPCs and their derivatives during definitive hematopoiesis. We also observed significant signs of HSPC apoptosis in the caudal hematopoietic tissue of bcas2 -/- zebrafish, which may be rescued by suppression of p53. Furthermore, we show that the bcas2 deletion induces an abnormal alternative splicing of Mdm4 that predisposes cells to undergo p53-mediated apoptosis, which provides a mechanistic explanation of the deficiency observed in HSPCs. Our findings revealed a novel and vital role for BCAS2 during HSPC maintenance in zebrafish.


Assuntos
Embrião não Mamífero/embriologia , Desenvolvimento Embrionário , Células-Tronco Hematopoéticas/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados/embriologia , Animais Geneticamente Modificados/genética , Técnicas de Silenciamento de Genes , Proteínas de Neoplasias/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-30584456

RESUMO

Objectives: As current evidence of the effectiveness on acupuncture for primary dysmenorrhea (PD) is inconsistent, we aimed to critically appraise the evidence from relevant systematic reviews (SRs). Methods: SRs of randomized controlled trials (RCTs) concerning acupuncture and PD were searched in four databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and latest Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklists were used to assess reporting characteristics and methodological quality, respectively. Results: The literature search yielded 38 potential records, of which five met the inclusion criteria. The total average (SD) for PRISMA was 20.60 (1.14) out of 27. All five SRs have more than one critical weakness in AMSTAR2, so their methodological qualities were considered as critically low. The most frequent problems included nonregistration of study protocol, absence of a list of excluded studies, and unclear acknowledgment of conflicts of interests. The three studies of higher methodological quality reported positive results in pain relief. Conclusion: The reporting and methodological quality of systematic reviews and meta-analysis studies were suboptimal, which demands further improvement. More efforts are needed to improve validity of systematic reviews and RCTs in this area.

11.
Hum Genet ; 137(10): 779-794, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30242501

RESUMO

Most cases of Usher syndrome type II (USH2) are due to mutations in the USH2A gene. There are no effective treatments or ideal animal models for this disease, and the pathological mechanisms of USH2 caused by USH2A mutations are still unknown. Here, we constructed a ush2a knockout (ush2a-/-) zebrafish model using TALEN technology to investigate the molecular pathology of USH2. An early onset auditory disorder and abnormal morphology of inner ear stereocilia were identified in the ush2a-/- zebrafish. Consequently, the disruption of Ush2a in zebrafish led to a hearing impairment, like that in mammals. Electroretinography (ERG) test indicated that deletion of Ush2a affected visual function at an early stage, and histological analysis revealed that the photoreceptors progressively degenerated. Rod degeneration occurred prior to cone degeneration in ush2a-/- zebrafish, which is consistent with the classical description of the progression of retinitis pigmentosa (RP). Destruction of the outer segments (OSs) of rods led to the down-regulation of phototransduction cascade proteins at late stage. The expression of Ush1b and Ush1c was up-regulated when Ush2a was null. We also found that disruption of fibronectin assembly at the retinal basement membrane weakened cell adhesion in ush2a-/- mutants. In summary, for the first time, we generated a ush2a knockout zebrafish line with auditory disorder and retinal degeneration which mimicked the symptoms of patients, and revealed that disruption of fibronectin assembly may be one of the factors underlying RP. This model may help us to better understand the pathogenic mechanism and find treatment for USH2 in the future.


Assuntos
Proteínas da Matriz Extracelular , Técnicas de Inativação de Genes , Síndromes de Usher , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Modelos Animais de Doenças , Eletrorretinografia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Síndromes de Usher/genética , Síndromes de Usher/metabolismo , Síndromes de Usher/patologia , Síndromes de Usher/fisiopatologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
12.
Cochrane Database Syst Rev ; 6: CD012409, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29926474

RESUMO

BACKGROUND: Cerebral palsy is an umbrella term that encompasses disorders of movement and posture attributed to non-progressive disturbances occurring in the developing foetal or infant brain. As there are diverse risk factors and aetiologies, no one strategy will prevent cerebral palsy. Therefore, there is a need to systematically consider all potentially relevant interventions for prevention. OBJECTIVES: PrimaryTo summarise the evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions for preventing cerebral palsy (reducing cerebral palsy risk).SecondaryTo summarise the evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions that may increase cerebral palsy risk. METHODS: We searched the Cochrane Database of Systematic Reviews (27 November 2016) for reviews of neonatal interventions reporting on cerebral palsy. Two review authors assessed reviews for inclusion, extracted data, and assessed review quality (using AMSTAR and ROBIS) and quality of the evidence (using the GRADE approach). Reviews were organised by topic; findings were summarised in text and were tabulated. Interventions were categorised as effective (high-quality evidence of effectiveness); possibly effective (moderate-quality evidence of effectiveness); ineffective (high-quality evidence of harm); probably ineffective (moderate-quality evidence of harm or lack of effectiveness); and no conclusions possible (low- to very low-quality evidence). MAIN RESULTS: Forty-three Cochrane Reviews were included. A further 102 reviews pre-specified the outcome cerebral palsy, but none of the included randomised controlled trials (RCTs) reported this outcome. Included reviews were generally of high quality and had low risk of bias, as determined by AMSTAR and ROBIS. These reviews involved 454 RCTs; data for cerebral palsy were available from 96 (21%) RCTs involving 15,885 children. Review authors considered interventions for neonates with perinatal asphyxia or with evidence of neonatal encephalopathy (3); interventions for neonates born preterm and/or at low or very low birthweight (33); and interventions for other specific groups of 'at risk' neonates (7). Quality of evidence (GRADE) ranged from very low to high.Interventions for neonates with perinatal asphyxia or with evidence of neonatal encephalopathyEffective interventions: high-quality evidence of effectivenessResearchers found a reduction in cerebral palsy following therapeutic hypothermia versus standard care for newborns with hypoxic ischaemic encephalopathy (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.54 to 0.82; seven trials; 881 children).No conclusions possible: very low-quality evidenceOne review observed no clear differences in cerebral palsy following therapeutic hypothermia versus standard care.Interventions for neonates born preterm and/or at low or very low birthweightPossibly effective interventions: moderate-quality evidence of effectivenessResearchers found a reduction in cerebral palsy with prophylactic methylxanthines (caffeine) versus placebo for endotracheal extubation in preterm infants (RR 0.54, 95% CI 0.32 to 0.92; one trial; 644 children).Probably ineffective interventions: moderate-quality evidence of harmResearchers reported an increase in cerebral palsy (RR 1.45, 95% CI 1.06 to 1.98; 12 trials; 1452 children) and cerebral palsy in assessed survivors (RR 1.50, 95% CI 1.13 to 2.00; 12 trials; 959 children) following early (at less than eight days of age) postnatal corticosteroids versus placebo or no treatment for preventing chronic lung disease in preterm infants.Probably ineffective interventions: moderate-quality evidence of lack of effectivenessTrial results showed no clear differences in cerebral palsy following ethamsylate versus placebo for prevention of morbidity and mortality in preterm or very low birthweight infants (RR 1.13, 95% CI 0.64 to 2.00; three trials, 532 children); volume expansion versus no treatment (RR 0.76, 95% CI 0.48 to 1.20; one trial; 604 children); gelatin versus fresh frozen plasma (RR 0.94, 95% CI 0.52 to 1.69; one trial, 399 children) for prevention of morbidity and mortality in very preterm infants; prophylactic indomethacin versus placebo for preventing mortality and morbidity in preterm infants (RR 1.04, 95% CI 0.77 to 1.40; four trials; 1372 children); synthetic surfactant versus placebo for respiratory distress syndrome in preterm infants (RR 0.76, 95% CI 0.55 to 1.05; five trials; 1557 children); or prophylactic phototherapy versus standard care (starting phototherapy when serum bilirubin reached a pre-specified level) for preventing jaundice in preterm or low birthweight infants (RR 0.96, 95% CI 0.50 to 1.85; two trials; 756 children).No conclusions possible: low- to very low-quality evidenceNo clear differences in cerebral palsy were observed with interventions assessed in 21 reviews.Interventions for other specific groups of 'at risk' neonatesNo conclusions possible: low- to very low-quality evidenceReview authors observed no clear differences in cerebral palsy with interventions assessed in five reviews. AUTHORS' CONCLUSIONS: This overview summarises evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions on cerebral palsy, and can be used by researchers, funding bodies, policy makers, clinicians, and consumers to aid decision-making and evidence translation. To formally assess other benefits and/or harms of included interventions, including impact on risk factors for cerebral palsy, review of the included Reviews is recommended.Therapeutic hypothermia versus standard care for newborns with hypoxic ischaemic encephalopathy can prevent cerebral palsy, and prophylactic methylxanthines (caffeine) versus placebo for endotracheal extubation in preterm infants may reduce cerebral palsy risk. Early (at less than eight days of age) postnatal corticosteroids versus placebo or no treatment for preventing chronic lung disease in preterm infants may increase cerebral palsy risk.Cerebral palsy is rarely identified at birth, has diverse risk factors and aetiologies, and is diagnosed in approximately one in 500 children. To date, only a small proportion of Cochrane Systematic Reviews assessing neonatal interventions have been able to report on this outcome. There is an urgent need for long-term follow-up of RCTs of such interventions addressing risk factors for cerebral palsy (through strategies such as data linkage with registries) and for consideration of the use of relatively new interim assessments (including the General Movements Assessment). Such RCTs must be rigorous in their design and must aim for consistency in cerebral palsy outcome measurement and reporting to facilitate pooling of data and thus to maximise research efforts focused on prevention.


Assuntos
Paralisia Cerebral/prevenção & controle , Asfixia Neonatal/terapia , Encefalopatias/terapia , Humanos , Hipotermia Induzida , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Literatura de Revisão como Assunto
13.
Pharm Biol ; 56(1): 217-224, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29560767

RESUMO

CONTEXT: Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment. OBJECTIVE: This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined. A TLE model was then created via bilateral intrahippocampal injection of 0.35 µg kainic acid (KA). Rats received CDDP (85 mg/kg), CBZ (100 mg/kg) or combined (85 mg/kg CDDP +100 mg/kg CBZ) via intragastric administration for 90 d, respectively. Seizure intensity, apoptosis and glial cell line-derived neurotrophic factor (GDNF) were measured. Furthermore, the improvement in cognitive impairment and hippocampal neuronal damage was evaluated. RESULTS: CDDP combined with CBZ significantly decreased seizure severity and frequency (p < 0.05) and ameliorated cognitive impairment (p < 0.05). The model group showed a significant reduction of neurons and Bcl-2/Bax expression in the hippocampus CA3 area (p < 0.01), the combined groups significantly reversed these change (p < 0.01). GDNF expression in the combined groups showed a clear increase over the model group (p < 0.05). CONCLUSION: These findings support the use of CDDP as an adjuvant drug for the treatment of TLE and cognitive deficit. Its mechanism might be related to an anti-apoptosis effect and up-regulation of GDNF.


Assuntos
Anticonvulsivantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Região CA3 Hipocampal/efeitos dos fármacos , Carbamazepina/farmacologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Epilepsia do Lobo Temporal/prevenção & controle , Ácido Caínico , Animais , Apoptose/efeitos dos fármacos , Região CA3 Hipocampal/metabolismo , Região CA3 Hipocampal/patologia , Região CA3 Hipocampal/fisiopatologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Modelos Animais de Doenças , Quimioterapia Combinada , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Reação de Fuga/efeitos dos fármacos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismo
14.
Cochrane Database Syst Rev ; 11: CD010443, 2017 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29129039

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a wide range of adverse health consequences for women and their infants in the short and long term. With an increasing prevalence of GDM worldwide, there is an urgent need to assess strategies for GDM prevention, such as combined diet and exercise interventions. This is an update of a Cochrane review that was first published in 2015. OBJECTIVES: To assess the effects of diet interventions in combination with exercise interventions for pregnant women for preventing GDM, and associated adverse health consequences for the mother and her infant/child. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 November 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs, comparing combined diet and exercise interventions with no intervention (i.e. standard care), that reported on GDM diagnosis as an outcome. Quasi-RCTs were excluded. Cross-over trials were not eligible for inclusion. We planned to include RCTs comparing two or more different diet/exercise interventions, however none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, assessed the risk of bias of the included trials and assessed quality of evidence for selected maternal and infant/child outcomes using the GRADE approach. We checked data for accuracy. MAIN RESULTS: In this update, we included 23 RCTs (involving 8918 women and 8709 infants) that compared combined diet and exercise interventions with no intervention (standard care). The studies varied in the diet and exercise programs evaluated and health outcomes reported. None reported receiving funding from a drug manufacturer or agency with interests in the results. Overall risk of bias was judged to be unclear due to the lack of methodological detail reported. Most studies were undertaken in high-income countries.For our primary review outcomes, there was a possible reduced risk of GDM in the diet and exercise intervention group compared with the standard care group (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.71 to 1.01; 6633 women; 19 RCTs; Tau² = 0.05; I² = 42%; P = 0.07; moderate-quality evidence). There was also a possible reduced risk of caesarean section (RR 0.95, 95% CI 0.88 to 1.02; 6089 women; 14 RCTs; moderate-quality evidence). No clear differences were seen between groups for pre-eclampsia (RR 0.98, 95% CI 0.79 to 1.22; 5366 participants; 8 RCTs; low-quality evidence), pregnancy-induced hypertension and/or hypertension (average RR 0.78, 95% CI 0.47 to 1.27; 3073 participants; 6 RCTs; Tau² = 0.19; I² = 62%; very low-quality evidence), perinatal mortality (RR 0.82, 95% CI 0.42 to 1.63; 3757 participants; 2 RCTs; low-quality evidence) or large-for-gestational age (RR 0.93, 95% CI 0.81 to 1.07; 5353 participants; 11 RCTs; low-quality evidence). No data were reported for infant mortality or morbidity composite.Subgroup analyses (based on trial design, maternal body mass index (BMI) and ethnicity) revealed no clear differential treatment effects. We were unable to assess the impact of maternal age, parity and specific features of the diet and exercise interventions. Findings from sensitivity analyses (based on RCT quality) generally supported those observed in the main analyses. We were not able to perform subgroup analyses based on maternal age, parity or nature of the exercise/dietary interventions due to the paucity of information/data on these characteristics and the inability to meaningfully group intervention characteristics.For most of the secondary review outcomes assessed using GRADE, there were no clear differences between groups, including for perineal trauma (RR 1.27, 95% CI 0.78 to 2.05; 2733 participants; 2 RCTs; moderate-quality evidence), neonatal hypoglycaemia (average RR 1.42, 95% CI 0.67 to 2.98; 3653 participants; 2 RCTs; Tau² = 0.23; I² = 77%; low quality evidence); and childhood adiposity (BMI z score) (MD 0.05, 95% CI -0.29 to 0.40; 794 participants; 2 RCTs; Tau² = 0.04; I² = 59%; low-quality evidence). However, there was evidence of less gestational weight gain in the diet and exercise intervention group compared with the control group (mean difference (MD) -0.89 kg, 95% CI -1.39 to -0.40; 5052 women; 16 RCTs; Tau² = 0.37; I² = 43%;moderate-quality evidence). No data were reported for maternal postnatal depression or type 2 diabetes; childhood/adulthood type 2 diabetes, or neurosensory disability. AUTHORS' CONCLUSIONS: Moderate-quality evidence suggests reduced risks of GDM and caesarean section with combined diet and exercise interventions during pregnancy as well as reductions in gestational weight gain, compared with standard care. There were no clear differences in hypertensive disorders of pregnancy, perinatal mortality, large-for-gestational age, perineal trauma, neonatal hypoglycaemia, and childhood adiposity (moderate- tovery low-quality evidence).Using GRADE methodology, the evidence was assessed as moderate to very low quality. Downgrading decisions were predominantly due to design limitations (risk of bias), and imprecision (uncertain effect estimates, and at times, small sample sizes and low event rates), however two outcomes (pregnancy-induced hypertension/hypertension and neonatal hypoglycaemia), were also downgraded for unexplained inconsistency (statistical heterogeneity).Due to the variability of the diet and exercise components tested in the included studies, the evidence in this review has limited ability to inform practice. Future studies could describe the interventions used in more detail, if and how these influenced behaviour change and ideally be standardised between studies. Studies could also consider using existing core outcome sets to facilitate more standardised reporting.


Assuntos
Diabetes Gestacional/prevenção & controle , Dieta , Exercício Físico , Cesárea/estatística & dados numéricos , Terapia Combinada/métodos , Feminino , Humanos , Hipertensão/epidemiologia , Recém-Nascido , Mortalidade Perinatal , Períneo/lesões , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Cell Physiol Biochem ; 43(3): 1207-1219, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28977800

RESUMO

BACKGROUND/AIMS: Inhibition of the repair of 5-fluorouracil (5-FU)-induced DNA lesions may improve the responses of tumors to anticancer agents. XRCC2 is a key factor in DNA repair. However, the role of XRCC2 in the chemoresistance of colorectal cancer (CRC) treated with 5-FU remains unclear. The aim of this study is to investigate whether XRCC2 expression affects the chemosensitivity of colorectal cancer. METHODS: XRCC2 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of XRCC2 expression. Following treatment with 5-FU, the effect of XRCC2 on proliferation was evaluated via a CCK-8 assay, the effects on cell cycle distribution and apoptosis were analyzed using flow cytometry, and γH2AX foci formation assays were performed to examine the influence of 5-FU on DNA Double-strand breaks(DSBs) repair in CRC cells. RESULTS: XRCC2 expression in CRC tissues was significantly higher than that in normal tissues, and this increased XRCC2 expression was associated with advanced T staging, M staging, TNM staging, Duke's staging, and greater liver and lymph node metastases. XRCC2 expression might be an independent prognostic indicator for CRC patients. Patients with negative XRCC2 expression exhibit greater sensitivity to treatment with 5-FU-based chemotherapy than those with positive XRCC2 expression. Moreover, our observations revealed that the knockdown of XRCC2 in CRC cells increased the sensitivities to 5-FU in terms of cell proliferation, apoptosis and cell cycle arrest. DNA DSBs repair was slower in the XRCC2-deficient cells than in the XRCC2-wild type cells. CONCLUSION: Our study demonstrated that XRCC2 might play an important role in CRC and function as a novel prognostic indicator and that the down-regulation of XRCC2 may be useful for sensitizing CRC cells during 5-FU chemotherapy.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Quinase do Ponto de Checagem 2/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Leucovorina/uso terapêutico , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Fosforilação/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Taxa de Sobrevida , Regulação para Cima/efeitos dos fármacos
16.
Cell Death Dis ; 8(10): e3082, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28981088

RESUMO

Cataract refers to opacities of the lens that impede the passage of light. Mutations in heat shock transcription factor 4 (HSF4) have been associated with cataract; however, the mechanisms regarding how mutations in HSF4 cause cataract are still obscure. In this study, we generated an hsf4 knockout zebrafish model using TALEN technology. The mutant zebrafish developed an early-onset cataract with multiple developmental defects in lens. The epithelial cells of the lens were overproliferated, resulting in the overabundance of lens fiber cells in hsf4null zebrafish lens. Consequently, the arrangement of the lens fiber cells became more disordered and irregular with age. More importantly, the terminal differentiation of the lens fiber cell was interrupted as the organelles cannot be cleaved in due time. In the cultured human lens epithelial cells, HSF4 could stabilize and retain p53 in the nucleus to activate its target genes such as fas cell surface death receptor (Fas) and Bcl-2-associated X apoptosis regulator (Bax). In the hsf4null fish, both p53 and activated-caspase3 were significantly decreased. Combined with the finding that the denucleation defect could be partially rescued through microinjection of p53, fas and bax mRNA into the mutant embryos, we directly proved that HSF4 promotes lens fiber cell differentiation by activating p53 and its downstream regulators. The data we presented suggest that apoptosis-related genes are involved in the lens fiber cell differentiation. Our finding that HSF4 functions in the upstream to activate these genes highlighted the new regulatory modes of HSF4 in the terminal differentiation of lens fiber cell.


Assuntos
Catarata/genética , Diferenciação Celular/genética , Fatores de Transcrição de Choque Térmico/genética , Proteína Supressora de Tumor p53/genética , Animais , Caspase 3/genética , Catarata/patologia , Linhagem Celular , Núcleo Celular/genética , Núcleo Celular/patologia , Proteínas de Ligação a DNA/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Cristalino/crescimento & desenvolvimento , Cristalino/metabolismo , Cristalino/patologia , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Proteína X Associada a bcl-2/genética , Receptor fas/genética
17.
Hum Mol Genet ; 26(12): 2335-2345, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28398482

RESUMO

In humans, CERKL mutations cause widespread retinal degeneration: early dysfunction and loss of rod and cone photoreceptors in the outer retina and, progressively, death of cells in the inner retina. Despite intensive efforts, the function of CERKL remains obscure and studies in animal models have failed to clarify the disease mechanism of CERKL mutations. To address this gap in knowledge, we have generated a stable CERKL knockout zebrafish model by TALEN technology and a 7bp deletion in CERKL cDNA that caused the premature termination of CERKL. These CERKL-/- animals showed progressive degeneration of photoreceptor outer segments (OSs) and increased apoptosis of retinal cells, including those in the outer and inner retinal layers. Additionally, we confirmed by immunofluorescence and western-blot that rod degeneration in CERKL-/- zebrafish occurred earlier and was more significant than that in cone cells. Accumulation of shed OSs in the interphotoreceptor matrix was observed by transmission election microscopy (TEM). This suggested that CERKL may regulate the phagocytosis of OSs by the retinal pigment epithelium (RPE). We further found that the phagocytosis-associated protein MERTK was significantly reduced in CERKL-/- zebrafish. Additionally, in ARPE-19 cell lines, knockdown of CERKL also decreased the mRNA and protein level of MERTK, as well as the ox-POS phagocytosis. We conclude that CERKL deficiency in zebrafish may cause rod-cone dystrophy, but not cone-rod dystrophy, while interfering with the phagocytosis function of RPE associated with down-regulation of the expression of MERTK.


Assuntos
Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Animais , Linhagem Celular , Regulação para Baixo , Técnicas de Inativação de Genes/métodos , Humanos , Mutação , Fagocitose/genética , Células Fotorreceptoras , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Retina/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Degeneração Retiniana/genética , Epitélio Pigmentado da Retina/metabolismo , Retinite Pigmentosa/metabolismo , Peixe-Zebra/genética
18.
Sci Rep ; 7: 46098, 2017 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-28378834

RESUMO

Mutations in EYS are associated with autosomal recessive retinitis pigmentosa (arRP) and autosomal recessive cone-rod dystrophy (arCRD) however, the function of EYS and the molecular mechanisms of how these mutations cause retinal degeneration are still unclear. Because EYS is absent in mouse and rat, and the structure of the retina differs substantially between humans and Drosophila, we utilised zebrafish as a model organism to study the function of EYS in the retina. We constructed an EYS-knockout zebrafish-line by TALEN technology which showed visual impairment at an early age, while the histological and immunofluorescence assays indicated the presence of progressive retinal degeneration with a cone predominately affected pattern. These phenotypes recapitulate the clinical manifestations of arCRD patients. Furthermore, the EYS-/- zebrafish also showed mislocalisation of certain outer segment proteins (rhodopsin, opn1lw, opn1sw1, GNB3 and PRPH2), and disruption of actin filaments in photoreceptors. Protein mislocalisation may, therefore, disrupt the function of cones and rods in these zebrafish and cause photoreceptor death. Collectively, these results point to a novel role for EYS in maintaining the morphological structure of F-actin and in protein transport, loss of this function might be the trigger for the resultant cellular events that ultimately lead to photoreceptor death.


Assuntos
Actinas/metabolismo , Distrofias de Cones e Bastonetes/metabolismo , Proteínas do Olho/metabolismo , Deleção de Genes , Segmento Externo da Célula Bastonete/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Envelhecimento/patologia , Animais , Apoptose , Sequência de Bases , Distrofias de Cones e Bastonetes/patologia , Distrofias de Cones e Bastonetes/fisiopatologia , Eletrorretinografia , Técnicas de Inativação de Genes , Transdução de Sinal Luminoso , Segmento Externo da Célula Bastonete/patologia , Segmento Externo da Célula Bastonete/ultraestrutura , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Visão Ocular
19.
Cochrane Database Syst Rev ; 2: CD009275, 2017 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-28236296

RESUMO

BACKGROUND: Dietary advice is the main strategy for managing gestational diabetes mellitus (GDM). It remains unclear what type of advice is best. OBJECTIVES: To assess the effects of different types of dietary advice for women with GDM for improving health outcomes for women and babies. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (8 March 2016), PSANZ's Trials Registry (22 March 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials comparing the effects of different types of dietary advice for women with GDM. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias, and extracted data. Evidence quality for two comparisons was assessed using GRADE, for primary outcomes for the mother: hypertensive disorders of pregnancy; caesarean section; type 2 diabetes mellitus; and child: large-for-gestational age; perinatal mortality; neonatal mortality or morbidity composite; neurosensory disability; secondary outcomes for the mother: induction of labour; perineal trauma; postnatal depression; postnatal weight retention or return to pre-pregnancy weight; and child: hypoglycaemia; childhood/adulthood adiposity; childhood/adulthood type 2 diabetes mellitus. MAIN RESULTS: In this update, we included 19 trials randomising 1398 women with GDM, at an overall unclear to moderate risk of bias (10 comparisons). For outcomes assessed using GRADE, downgrading was based on study limitations, imprecision and inconsistency. Where no findings are reported below for primary outcomes or pre-specified GRADE outcomes, no data were provided by included trials. Primary outcomes Low-moderate glycaemic index (GI) versus moderate-high GI diet (four trials): no clear differences observed for: large-for-gestational age (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.22 to 2.34; two trials, 89 infants; low-quality evidence); severe hypertension or pre-eclampsia (RR 1.02, 95% CI 0.07 to 15.86; one trial, 95 women; very low-quality evidence); eclampsia (RR 0.34, 95% CI 0.01 to 8.14; one trial, 83 women; very low-quality evidence) or caesarean section (RR 0.66, 95% CI 0.29 to 1.47; one trial, 63 women; low-quality evidence). Energy-restricted versus no energy-restricted diet (three trials): no clear differences seen for: large-for-gestational age (RR 1.17, 95% CI 0.65 to 2.12; one trial, 123 infants; low-quality evidence); perinatal mortality (no events; two trials, 423 infants; low-quality evidence); pre-eclampsia (RR 1.00, 95% CI 0.51 to 1.97; one trial, 117 women; low-quality evidence); or caesarean section (RR 1.12, 95% CI 0.80 to 1.56; two trials, 420 women; low-quality evidence). DASH (Dietary Approaches to Stop Hypertension) diet versus control diet (three trials): no clear differences observed for: pre-eclampsia (RR 1.00, 95% CI 0.31 to 3.26; three trials, 136 women); however there were fewer caesarean sections in the DASH diet group (RR 0.53, 95% CI 0.37 to 0.76; two trials, 86 women). Low-carbohydrate versus high-carbohydrate diet (two trials): no clear differences seen for: large-for-gestational age (RR 0.51, 95% CI 0.13 to 1.95; one trial, 149 infants); perinatal mortality (RR 3.00, 95% CI 0.12 to 72.49; one trial, 150 infants); maternal hypertension (RR 0.40, 95% CI 0.13 to 1.22; one trial, 150 women); or caesarean section (RR 1.29, 95% CI 0.84 to 1.99; two trials, 179 women). High unsaturated fat versus low unsaturated fat diet (two trials): no clear differences observed for: large-for-gestational age (RR 0.54, 95% CI 0.21 to 1.37; one trial, 27 infants); pre-eclampsia (no cases; one trial, 27 women); hypertension in pregnancy (RR 0.54, 95% CI 0.06 to 5.26; one trial, 27 women); caesarean section (RR 1.08, 95% CI 0.07 to 15.50; one trial, 27 women); diabetes at one to two weeks (RR 2.00, 95% CI 0.45 to 8.94; one trial, 24 women) or four to 13 months postpartum (RR 1.00, 95% CI 0.10 to 9.61; one trial, six women). Low-GI versus high-fibre moderate-GI diet (one trial): no clear differences seen for: large-for-gestational age (RR 2.87, 95% CI 0.61 to 13.50; 92 infants); caesarean section (RR 1.91, 95% CI 0.91 to 4.03; 92 women); or type 2 diabetes at three months postpartum (RR 0.76, 95% CI 0.11 to 5.01; 58 women). Diet recommendation plus diet-related behavioural advice versus diet recommendation only (one trial): no clear differences observed for: large-for-gestational age (RR 0.73, 95% CI 0.25 to 2.14; 99 infants); or caesarean section (RR 0.78, 95% CI 0.38 to 1.62; 99 women). Soy protein-enriched versus no soy protein diet (one trial): no clear differences seen for: pre-eclampsia (RR 2.00, 95% CI 0.19 to 21.03; 68 women); or caesarean section (RR 1.00, 95% CI 0.57 to 1.77; 68 women). High-fibre versus standard-fibre diet (one trial): no primary outcomes reported. Ethnic-specific versus standard healthy diet (one trial): no clear differences observed for: large-for-gestational age (RR 0.14, 95% CI 0.01 to 2.45; 20 infants); neonatal composite adverse outcome (no events; 20 infants); gestational hypertension (RR 0.33, 95% CI 0.02 to 7.32; 20 women); or caesarean birth (RR 1.20, 95% CI 0.54 to 2.67; 20 women). Secondary outcomes For secondary outcomes assessed using GRADE no differences were observed: between a low-moderate and moderate-high GI diet for induction of labour (RR 0.88, 95% CI 0.33 to 2.34; one trial, 63 women; low-quality evidence); or an energy-restricted and no energy-restricted diet for induction of labour (RR 1.02, 95% CI 0.68 to 1.53; one trial, 114 women, low-quality evidence) and neonatal hypoglycaemia (average RR 1.06, 95% CI 0.48 to 2.32; two trials, 408 infants; very low-quality evidence).Few other clear differences were observed for reported outcomes. Longer-term health outcomes and health services use and costs were largely not reported. AUTHORS' CONCLUSIONS: Evidence from 19 trials assessing different types of dietary advice for women with GDM suggests no clear differences for primary outcomes and secondary outcomes assessed using GRADE, except for a possible reduction in caesarean section for women receiving a DASH diet compared with a control diet. Few differences were observed for secondary outcomes.Current evidence is limited by the small number of trials in each comparison, small sample sizes, and variable methodological quality. More evidence is needed to assess the effects of different types of dietary advice for women with GDM. Future trials should be adequately powered to evaluate short- and long-term outcomes.


Assuntos
Diabetes Gestacional/dietoterapia , Restrição Calórica , Cesárea/estatística & dados numéricos , Dieta com Restrição de Carboidratos , Dieta para Diabéticos , Carboidratos da Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Feminino , Índice Glicêmico , Humanos , Hipertensão/epidemiologia , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Sci Rep ; 6: 24226, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27052676

RESUMO

Disseminated superficial porokeratosis (DSP) is a rare keratinization disorder of the epidermis. It is characterized by keratotic lesions with an atrophic center encircled by a prominent peripheral ridge. We investigated the genetic basis of DSP in two five-generation Chinese families with members diagnosed with DSP. By whole-exome sequencing, we sequencing identified a nonsense variation c.412C > T (p.Arg138*) in the phosphomevalonate kinase gene (PMVK), which encodes a cytoplasmic enzyme catalyzing the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate in the mevalonate pathway. By co-segregation and haplotype analyses as well as exclusion testing of 500 normal control subjects, we demonstrated that this genetic variant was involved in the development of DSP in both families. We obtained further evidence from studies using HaCaT cells as models that this variant disturbed subcellular localization, expression and solubility of PMVK. We also observed apparent apoptosis in and under the cornoid lamella of PMVK-deficient lesional tissues, with incomplete differentiation of keratinocytes. Our findings suggest that PMVK is a potential novel gene involved in the pathogenesis of DSP and PMVK deficiency or abnormal keratinocyte apoptosis could lead to porokeratosis.


Assuntos
Genes Dominantes , Predisposição Genética para Doença/genética , Mutação , Fosfotransferases (Aceptor do Grupo Fosfato)/genética , Poroceratose/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Sequência de Bases , Linhagem Celular , Criança , Pré-Escolar , China , Análise Mutacional de DNA , Saúde da Família , Feminino , Predisposição Genética para Doença/etnologia , Humanos , Masculino , Microscopia Confocal , Linhagem , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Poroceratose/enzimologia , Poroceratose/etnologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA