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1.
Orphanet J Rare Dis ; 14(1): 206, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429781

RESUMO

BACKGROUND: Sirolimus has been confirmed to be effective for lymphangioleiomyomatosis (LAM), a rare multisystem neoplastic disease in women. The long-term effects of sirolimus treatment for LAM, however, are largely unknown. We aimed to analyze the long-term efficacy and safety of sirolimus therapy for LAM with 4-year follow-up. METHODS: In total, 142 sporadic LAM patients who took sirolimus for 1-4 years were retrospectively enrolled for this analysis. The variables used for analysis included pulmonary function tests, arterial blood gas analysis, 6-min walking distance (6MWD), St. George's Respiratory Questionnaires (SGRQ) and serum vascular endothelial growth factor-D (VEGF-D) levels before and after the initiation of sirolimus therapy. The rates of change (slope) in those variables were calculated, and adverse events were also analyzed. RESULTS: In total, 122, 83, 60 and 32 patients out of 142 were followed for 1, 2, 3 and 4 years respectively. Sirolimus treatment improved the change rate in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) compared with the data before treatment (FEV1, - 10 ± 15 vs. - 178 ± 36 ml/y, P <  0.001 and FVC, 54 ± 22 vs.-72 ± 68 ml/y, P < 0.05). In comparison to the baseline measurements, significant improvements were observed in FEV1 at the first year; FVC at 1-2 years; arterial oxygen levels, 6MWD, and SGRQ at 1-3 years; and VEGF-D at 1-4 years. Overall, all variables stabilized or improved during the 4 years of observation. Adverse events related to sirolimus were mild. CONCLUSION: Sirolimus therapy is effective at improving or stabilizing pulmonary function, oxygen levels, exercise capacity, and quality of life in patients with LAM for up to 4 years. VEGF-D is maintained at a lower level for 4 years after treatment. Adverse events related to sirolimus were mild.

2.
Yi Chuan ; 41(7): 582-598, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31307968

RESUMO

Gene editing is a genetic manipulation technology which utilizes bacterial nucleases to accurately and efficiently modify DNA or RNA. Gene editing has broad applications in basic research, breeding, and drug screening, and it is gaining validity and applicability to the therapy of many diseases especially genetic-based disease. In this review, we summarize the development of gene editing technology, its different strategies and applications in the treatment of disease, and the research of gene editing therapy for genetic diseases (including base editor and epigenetic regulation) in the treatment of disorders and diseases of the blood system, liver, muscle and nervous system. Finally, we discuss the future development prospects of gene editing therapy.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/tendências , Terapia Genética , Doença , Epigênese Genética , Humanos
3.
Vet Microbiol ; 235: 143-150, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282372

RESUMO

Porcine parvovirus (PPV) is one of the major pathogens that bring about reproductive failure of pregnant sows. However, the study of the pathogenesis mechanism is circumscribed due to the lack of efficient genetic manipulation method. Infectious clone is a powerful tool for further studying the genetic mechanisms of PPV. In the present study, the gene fragment (157-4812) of PPV was amplified by PPV China isolate strain as a template, and PPV DNA fragments (1-182) forming Y-structure within in 5' end and (4788-5074) forming U-structure in 3' end were synthesized. And then, the above three fragments were inserted into plasmid pKQLL to congregate a PPV full-length recombinant plasmid by means of In-Fusion cloning technology. After the successful sequencing identification of the recombinant plasmid, the EcoR I restriction site was brought out as a genetic marker by nonsense mutation (A3058 T) to produce plasmid Y-PPV, which was transfected into PK-15 cells for rescue of virus. The rescued viral particles were observed under transmission electron microscopy, and the sequencing analysis showed that Y-PPV could stably carry the genetic marker. It could be seen that Y-PPV has similar replicate capability and pathogenicity as the wild-type parental PPV strain by cellular and animal experiments. These results confirmed that Y-PPV maintain similar biological characteristics with wild-type parental PPV strain. Infectious clone could be a valuable tool for studying the individual genes of PPV and applications in gene deletion or live vector vaccines.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 893-898, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204950

RESUMO

OBJECTIVE: To investigate the gene mutation types and spectrum of α, ß-thalassemia in Fuzhou area of China. METHODS: Thalassemia gene screening was performed in the women receiving physical, prenatal, and pre-pregnancy examination, and the patients with suspected thalassemia in our hospital from July 2013 to March 2018.Genotypes of thalassem were detected by Gap-PCR and RDB-PCR. RESULTS: 1042 were positive among 2074 suspected cases with a positive rate of 50.24%; 618 cases were confirmed to be α-thalassemia and with a positive rate of 29.8%; 409 cases were confirmed to be ß-thalassemia with a positive rate of 19.72%. 15 cases were confirmed to be α-ß complex thalassemia with a positive rate of 0.72%. the --SEA/αα(76.54%) was the most common genotype among α-thalassemia, -α3.7/αα(10.03%) and -α4.2/αα(2.91%) in hot pursuit. In addition, IVS-II-55 (T->G) and IVS-II-119 (-G, +CTCGGCCC) were newly found alpha mutations; the IVS-2-654 (C→T) (40.83%) was the most common genotype among ß-thalassemia, CD41-42 (-TCTT) (35.94%) and CD17 (A→T) (9.78%) in hot pursuit. CONCLUSION: The genotype of thalassemia in Fuzhou area is highly heterogenic, --SEA/αα is the most common genotype among α-thalassemia, IVS-2-654 (C→T) is the most common genotype among ß-thalassemia, Meanwhile, two α-mutation sites are found in this study which were not reported in the Database of Human Hemoglobin Variants and Thalassemias.


Assuntos
Talassemia alfa , Talassemia beta , China , Feminino , Genótipo , Humanos , Mutação , Gravidez
5.
Biomed Pharmacother ; 115: 108816, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31096144

RESUMO

OBJECTIVE: Inflammation and immune responses are crucial factors associated with the onset and progression of stroke. Interleukin-11 (IL-11) is a hematopoietic IL-6 family cytokine that functions as an anti-inflammatory agent against various inflammatory diseases. However, its roles in stroke remain unknown. In this study, we investigated the effects of IL-11 on cerebral ischemia-reperfusion injury in a model of focal cerebral ischemia. METHODS: Mice were randomly divided into five groups the vehicle group, the middle cerebral artery occlusion (MCAO) group, the MCAO plus adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C group, the MCAO plus IL-11 treatment group, and the MCAO plus IL-11 treatment and compound C group. Focal cerebral ischemia was induced by occluding the left middle cerebral artery, and reperfusion was achieved by withdrawing the suture 2 h after ischemia. The protein expression levels of IL-11 were measured using Western blot analysis, and its location was detected using immunohistochemistry and immunofluorescence staining. The infarct volume was examined using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the neurobehavioral progression was assessed using the neurological scoring system. The expression of astrocytes and microglia was detected using immunochemistry, and real-time quantitative PCR was used for the gene quantification of inflammatory cytokines. The extent of cerebral ischemia-reperfusion injury was tested using Nissl staining and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of the apoptotic proteins Bax, Bcl-2 and cleaved caspase-3 were detected using Western blot analysis, and the oxidative stress was also measured. RESULTS: The expression of IL-11 mRNA and protein significantly decreased after cerebral ischemia. Immunohistochemical staining showed a large amount of IL-11 in the cerebral cortex of the mice in the vehicle group, whereas the immunoreactivity of IL-11 remained weak for 24 h in the MCAO group. Immunofluorescent staining further confirmed that IL-11 was mainly expressed in the neurons. It was suggested that IL-11 (20 µg/kg) treatment ameliorated infarction and reduced neurological scores. In addition, IL-11 proved to reduce neuropathic damage, glial activation, and the expression of proinflammatory cytokines and increase the expression of anti-inflammatory cytokines after cerebral ischemia. IL-11 was also able to alleviate oxidative stress caused by cerebral ischemia, and AMPK inhibition enhanced the alleviation. Moreover, IL-11 was found to inhibit apoptosis caused by cerebral ischemia, which could also be facilitated by AMPK inhibitors. SIGNIFICANCE: Our research suggests that IL-11 is decreased during cerebral ischemia-reperfusion injury, but IL-11 treatment can improve neurological function and reduce the cerebral infarct volume, which can trigger stroke in mice. AMPK inhibition can further promote the protective effect of IL-11 in stroke. Overall, we demonstrate that IL-11 is of therapeutic interest in controlling stroke and managing cerebral ischemia-reperfusion injury.

6.
Ecotoxicol Environ Saf ; 177: 100-107, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30974243

RESUMO

Contamination of vegetable plants with cadmium (Cd) has become a serious issue in recent years. In the present study, pakchoi (Brassica chinensis L.) grown in Cd-contaminated soil inoculated with abscisic acid (ABA)-generating bacteria, Azospirillum brasilense and Bacillus subtilis, showed 28%-281% and 26%-255% greater biomass, and 40%-79% and 43%-77% lower Cd concentrations, respectively, than those of the controlbacteria-free plants. These treatments also alleviated the Cd-induced photosynthesis inhibition and oxidative damage (indicated by malondialdehyde [MDA], H2O2, and O2• -). Furthermore, the application of bacteria also remarkably improved the levels of antioxidant-related compounds (total phenolics, total flavonoids, ascorbate, and 2,2-diphenyl-1-picrylhydrazyl [DPPH] activity) and nutritional quality (soluble sugar and soluble protein) in the Cd-supplied plants. Based on these results, we conclude that the application of ABA-generating bacteria might be an alternative strategy for improving the biomass production and quality of vegetable plants grown in Cd-contaminated soil.


Assuntos
Ácido Abscísico/biossíntese , Brassica/metabolismo , Cádmio/análise , Poluentes do Solo/análise , Antioxidantes/metabolismo , Azospirillum brasilense/metabolismo , Bacillus subtilis/metabolismo , Brassica/microbiologia , Cádmio/metabolismo , Cádmio/toxicidade , Poluição Ambiental , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Solo/química , Microbiologia do Solo , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Verduras/crescimento & desenvolvimento , Verduras/metabolismo , Verduras/microbiologia
7.
J Med Chem ; 62(10): 4949-4966, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31026162

RESUMO

Pancreatic cancer is one of the most common cancers with an extremely low survival rate. Metastasis, as one of the key reasons of cancer-related death, is found in more than 50% pancreatic cancer patients at diagnosis. Novel therapeutic targets and drugs blocking cancer metastasis are urgently needed. Herein, we report a series of 1,5-diaryl-1,2,4-triazole derivatives as potent antimetastatic agents. Lead compound 6y displayed effective antimetastatic activities in pancreatic cancer in vitro and in vivo. Concomitant studies indicated that 6y probably binds with myoferlin (MYOF), a novel potential antitumor metastasis target, which regulates vesicle trafficking and metastasis-related proteins. Subsequent biophysical and biochemical methods verified that 6y bound to MYOF. Mechanism studies revealed that 6y inhibited pancreatic cancer metastasis through reversing the epithelial mesenchymal transition, inhibiting the secretions of matrix metalloproteinase and blocking the receptor tyrosine kinases. Our findings suggest that targeting MYOF with 6y may be a promising therapeutic strategy to prevent pancreatic cancer metastasis.

8.
Medicine (Baltimore) ; 98(14): e15039, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30946344

RESUMO

RATIONALE: Amyloidosis secondary to intrapulmonary Castleman disease (CD) is a rare benign disease diagnosed by histopathology. It seems to be associated with chronic inflammation, and large amounts of IL-6 produced in the germinal center of CD may enhance the production of precursor of amyloid. PATIENT CONCERNS: We reported a case of an 18-year-old woman presenting with dry cough and dyspnea on exertion for 6 months and detailed exams revealed multiple pulmonary nodules, positive antinuclear antibodies, hypocomplementemia, and thrombocytopenia. DIAGNOSES: A computed tomography-guided percutaneous lung biopsy revealed the histopathological features of pulmonary hyalinizing granuloma (PHG), but video-assisted pulmonary wedge resection for biopsy with immunohistochemical stains finally demonstrated a corrected diagnosis of intrapulmonary CD with secondary amyloidosis. INTERVENTIONS: The patient had received prednisone and Tacrolimus for 6 months. OUTCOMES: There was no significant improvement in pulmonary lesions or platelet level. Chemotherapy to CD was needed. LESSONS: Intrapulmonary CD should be considered in patients with multiple pulmonary nodules irresponsive to corticosteroid and diagnosis of PHG should be carefully considered based on small lung biopsy sample. The treatment of amyloidosis secondary to CD remains to be uncertain.


Assuntos
Amiloidose/diagnóstico , Hiperplasia do Linfonodo Gigante/diagnóstico , Granuloma/diagnóstico , Pneumopatias/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adolescente , Amiloidose/etiologia , Hiperplasia do Linfonodo Gigante/complicações , Diagnóstico Diferencial , Feminino , Humanos , Pneumopatias/complicações
9.
J Lipid Res ; 60(5): 1058-1064, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30902903

RESUMO

Vitamin D metabolite analysis possessed significant clinical value for the pediatric department. However, invasive venipuncture sampling and high blood consumption inflicted much suffering on patients. For alleviation, we carried out a LC-MS method for 25-hydroxyvitamin D quantification in only 3 µl of plasma from the considerably less invasive finger-prick blood samples. To improve sensitivity, acylation on C3-hydroxyl (by isonicotinoyl chloride) rather than Diels-Alder adduction on s-cis-diene structure was for the very first time introduced into vitamin D metabolite derivatization. Compared with the existing derivatization approaches, this novel strategy not only prevented isomer interference, but also exhibited higher reacting throughput. For certification, the methodology was systematically validated and showed satisfying consistency with SRM927a. During clinical application, we found a convincing correlation between 25-hydroxyvitamin D and indirect/total bilirubin in jaundiced newborns. Such an observation indicated that vitamin D supplementation may help to achieve optimal outcomes in neonatal jaundice.

10.
Medicine (Baltimore) ; 98(1): e14017, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608451

RESUMO

RATIONALE: Chronic eosinophilic pneumonia (CEP) is rare and an idiopathic disorder. The disease has been associated with drugs, infection, or irradiation, and its relationship with asthma remains unclear. PATIENT CONCERNS: We reported a case of a 49-year-old female patient after trastuzumab and radiation therapy for breast cancer. Two months after radiation treatment, the patient complained of productive cough, progressive breathlessness, occasional wheezing, and left pectoralgia. DIAGNOSES: Computed tomography (CT) scan revealed infiltrates in lungs. Without evidence of infection, marked increased eosinophils in a transbronchial biopsy performed from the left upper lobe confirmed the diagnosis of CEP after trastuzumab and radiation therapy. INTERVENTIONS: The patient was started with oral prednisone at 0.5 mg/kg/day. OUTCOMES: A CT scan of the chest obtained 2 weeks after steroid treatment showed diminishment of the lesions, and at the 6-month follow-up, the patient had no complaints of discomfort with no relapse of pulmonary lesions. LESSONS: Physicians should consider CEP as a diagnosis in patients who have had previous exposure to trastuzumab and radiation therapy, especially with a history of asthma. Timely diagnosis and treatment may benefit these patients.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Eosinofilia Pulmonar/induzido quimicamente , Radioterapia/efeitos adversos , Trastuzumab/efeitos adversos , Administração Oral , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/complicações , Neoplasias da Mama/radioterapia , Doença Crônica , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Eosinofilia Pulmonar/diagnóstico por imagem , Eosinofilia Pulmonar/tratamento farmacológico , Eosinofilia Pulmonar/patologia , Tomografia Computadorizada por Raios X/métodos , Trastuzumab/uso terapêutico , Resultado do Tratamento
11.
J Pharm Biomed Anal ; 162: 34-40, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30219597

RESUMO

BACKGROUND: Comprehensive serum sex hormone profiling is essential for monitoring the occurrence and development of many related diseases. However, the current methods for multi-class sex hormone detection were always lack of Standard Reference Material (SRM) certification and suffered from large sample consumption. For improvement, we developed a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method focused on SRM certification and minimization of serum consumption for simultaneous quantification of seven mainstream serum sex hormones including estrogens (estrone E1, estradiol E2 and estriol E3), androgens (testosterone T, androstenedione AD, dehydroepiandrosterone DHEA) and progestogens (progesterone P). METHODS: To achieve one-batch analysis, a straightforward strategy was designed and carefully optimized. Schematically, serum was firstly spiked with isotope-labeled internal standards. Then, liquid-liquid extraction was performed with methyl tert-butyl ether. After drying under nitrogen, dansyl chloride was introduced for derivatization. Finally, the mixture was submitted to LC-MS/MS for quantification. RESULTS: The limit of quantification was 0.005 ng/mL for E1, E2 and E3, 0.01 ng/mL for T, P and AD, 0.25 ng/mL for DHEA. Inter- and intra-assay CVs were less than 11.8%. The selectivity was proved satisfactory by interference spiking tests. With systematical SRM validation, the mean bias of -5.4 to 4.7% was observed, which indicated excellent method reliability. We found significant positive bias in chemiluminescence immunoassay (CLIA) detection comparing with current method, which promoted us to reconsider our previous results on sex hormone regulation in male patients with coronary atherosclerotic disease. After redetecting the related samples, modified and improved conclusions were proposed. CONCLUSIONS: A LC-MS/MS method for multi-class serum sex hormone profiling was developed with SRM certification and minimized serum consumption. Taking advantages of such reliable method, the previous CLIA-based research findings on sex hormone regulation in male patients with coronary atherosclerosis were modified and improved after redetecting the same sample-pool.


Assuntos
Análise Química do Sangue/métodos , Cromatografia Líquida , Doença da Artéria Coronariana/sangue , Hormônios Esteroides Gonadais/sangue , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Idoso , Androstenodiona/sangue , Androstenóis/sangue , Análise Química do Sangue/normas , Calibragem , Estudos de Casos e Controles , Cromatografia Líquida/normas , Doença da Artéria Coronariana/diagnóstico , Estranos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Progesterona/sangue , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray/normas , Espectrometria de Massas em Tandem/normas , Testosterona/sangue
12.
Med Teach ; : 1-3, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30462549

RESUMO

OBJECTIVE: To reflectively look at the present methods by which the clinical competence of 5th-year medical students (i.e. interns) in Sun Yat-Sen University (SYSU) are assessed upon finishing internship rotation in internal medicine (IM). METHODS: Current procedures for the competence assessment of end-of-rotation IM interns in the First Affiliated Hospital of SYSU were reviewed, along with a point-by-point appraisal based on the PROFILE approach to structured assessment, and, whenever possible, suggestions for future improvement. RESULTS AND DISCUSSIONS: On a scale of 1-10, with 10 being the best or the most ideal, our marks for current methods to assess end-of-rotation IM interns in terms of being Programmatic, Real-World, Outcome-based, Formative, Impactful, Learner-engaged, and Evaluation-guaranteed were 7, 9, 3, 4, 6, 8, and 1, respectively. The strengths, weaknesses as well as potential solutions in each of the seven aspects are also discussed separately. CONCLUSIONS: Current assessment program for IM internship is strong in being programmatic, real-world, educationally impactful and learner engaged, and has room for further improvement in its time-based arrangements, relative shortage of feedback provision, as well as a systematic lack of quality control measures.

13.
Endocrine ; 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30338480

RESUMO

BACKGROUND: Rathke's cleft cysts (RCC) are lesions that arise from Rathke's pouch. Though frequently incidental, resulting symptoms in a minority of cases are indicators for surgical resection, which may prove beneficial. OBJECTIVE: To characterize a cohort of surgically-resected RCC cases at Oregon Health & Science University; tabulate associated hormonal imbalances and symptoms, possible symptom reversal with surgery, determine recurrence risk; identify predictors of recurrence and headache improvement. METHOD: Electronic records of all RCC resected cases (from 2006-2016; 11 years) were retrospectively reviewed. Patients had been evaluated by one neuroendocrinologist using a uniform protocol. RESULTS: A pathological RCC diagnosis was established in 73 of 814 (9%) surgical pituitary cases. The RCC cohort was 77% (n = 56/73) female, mean age was 39.5 ± 14.9 years at first surgery, and at presentation headache was reported in 88% and visual defects/diplopia in 18% of patients. Initial RCC maximum diameter was 1.3 ± 0.7 cm. The most frequent hormonal deficit was cortisol; 24% of patients had a new adrenal insufficiency (AI) diagnosis, however, 36% also had AI at 3 months post-operatively. Mean follow up was 4.0 ± 4.5 years. Two-thirds of patients (41/62) had headache improvement 3 months post-operatively. Post-operative imaging revealed no residual cyst in 58% (38/65). In those patients with no residual RCC, 29% had recurrence and 71% had long lasting cure. From the 42% (27/65) of patients with residual cyst on post-operative imaging; 59% (16/27) remained stable, 26% (7/27) progressed and 15% (4/27) regressed. CONCLUSION: Symptomatic RCC present mostly in women, with a high proportion reporting headaches. Prevalence of AI at diagnosis is high. Surgery may not achieve adrenal axis recovery, but renders a high percentage of headache improvement. Approximately 25% of RCC will recur by 4 years postoperatively. Clinicians should cautiously screen patients with symptomatic RCC, regardless of lesion size for AI.

14.
Endocrinol Metab (Seoul) ; 33(3): 355-363, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30112867

RESUMO

BACKGROUND: The aim of this study was to investigate the factors associated with resolution of hypertension after adrenalectomy in patients with primary aldosteronism. A secondary aim was to describe our use of the contralateral ratio in adrenal venous sampling (AVS) in the setting of suboptimal successful cannulation rates. METHODS: A retrospective review of patients who underwent AVS followed by unilateral adrenalectomy for primary aldosteronism was performed. RESULTS: Complete resolution of hypertension and hypokalemia was seen in 17 of 40 patients (42.5%), while a clinical improvement in hypertension was seen in 38 of 40 (95%). Shorter duration of hypertension, mean aldosteronoma resolution score (ARS), and a high ARS of 3 to 5 were associated with resolution of hypertension after adrenalectomy (P=0.02, P=0.02, and P=0.004, respectively). Of the individual components of ARS, only a duration of hypertension of ≤6 years was associated with resolution of hypertension after adrenalectomy (P=0.03). CONCLUSION: A shorter duration of hypertension was significantly associated with resolution of hypertension after adrenalectomy in patients with primary aldosteronism.

15.
Opt Express ; 26(14): 18006-18018, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-30114081

RESUMO

We investigate the interest of combined process of reactive ion etching (RIE) and dynamic chemical etching (DCE) as a final step after polishing to improve the laser damage resistance of fused silica optics at the wavelength of 355 nm. The investigation is carried out on the polished fused silica optics by changing the RIE depth while keeping the DCE depth fixed. We evidence that the combined etching process can effectively remove the damage precursors on the fused silica surface and thus improve its laser-induced damage threshold exceeding the level of the deep HF-etched surface. The effects of the combined etching depth on the surface roughness and surface error are also studied systematically. We show that the combined shallow etching can achieve better overall surface quality. Deeper etching will cause surface quality degradation of the fused silica optics, which is believed to be associated with the chemical etching during the combined process. Given that HF acid processing will degrade the surface quality of fused silica optics, the combined shallow etching appears as a pertinent alternative to HF-based deep etching.

16.
J Lipid Res ; 59(9): 1783-1790, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30026263

RESUMO

Fat-soluble vitamins (FSVs), A, D, and E, are components of prenatal vitamin care. Previously, limited evidence existed to explain on a molecular level how maternal FSV supplementation affects the fetus during pregnancy. We developed a simplified LC-MS/MS method to simultaneously detect FSVs in maternal plasma (MP) and amniotic fluid (AF); we used this approach to investigate the correlation between FSV levels in these two matrices. With this method, we circumvented frequently used liquid-liquid extraction or solid-phase extraction methods and, instead, used simple protein precipitation with acetonitrile for sample preparation. This method displayed satisfactory linearity, intra- and inter-day imprecision, and accuracy. We validated the consistency with standard reference material 972a and 968f certification. In analysis of MP and AF samples from 50 pregnant women in the second trimester, concentrations of retinol, 25-hydroxyvitamin D3 [25(OH)D3], and α-tocopherol (reflecting vitamins A, D, and E, respectively) were lower in AF than in MP. Significant positive correlations existed between MP and AF for 25(OH)D3 (r = 0.667; P < 0.001) and retinol (r = 0.393; P = 0.005), but not for α-tocopherol (r = 0.145, P > 0.05). This novel LC-MS/MS method shows prominent applicability for FSV detection and the observed correlations contribute to research on fetal development.

17.
Cell Death Dis ; 9(6): 625, 2018 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-29795373

RESUMO

Transforming growth factor ß (TGF-ß) is critical for embryonic development, adult tissue homeostasis, and tumor progression. TGF-ß suppresses tumors at early stage, but promotes metastasis at later stage through oncogenes such as Twist1. Gamma-synuclein (SNCG) is overexpressed in a variety of invasive and metastatic cancer. Here, we show that TGF-ß induces SNCG expression by Smad-Twist1 axis, thus promoting TGF-ß- and Twist1-induced cancer cell migration and invasion. We identify multiple Twist1-binding sites (E-boxes) in SNCG promoter. Chromatin immunoprecipitation and luciferase assays confirm the binding of Twist1 to the E-boxes of SNCG promoter sequence (-129/-1026 bp). Importantly, the Twist1-binding site close to the transcription initiation site is critical for the upregulation of SNCG expression by TGF-ß and Twist1. Mutations of Twist1 motif on the SNCG promoter constructs markedly reduces the promoter activity. We further show that TGF-ß induces Twist1 expression through Smad thereby enhancing the binding of Twist1 to SNCG promoter, upregulating SNCG promoter activity and increasing SNCG expression. SNCG knockdown abrogates TGF-ß- or Twist1-induced cancer cell migration and invasion. Finally, SNCG knockdown inhibits the promotion of cancer metastasis by Twist1. Together, our data demonstrate that SNCG is a novel target of TGF-ß-Smad-Twist1 axis and a mediator of Twist1-induced cancer metastasis.

18.
Environ Sci Pollut Res Int ; 25(22): 21801-21810, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29796882

RESUMO

The retention of aquatic plant debris in freshwater systems favors a reduction in soluble reactive phosphorus (P) in overlying water through microbe-mediated mechanisms in sediment. For a more complete view of the changes in sediment microbial structure and functioning when receiving plant debris, the enzyme activities and microbial community structure in sediments incubated with or without plant debris were investigated. Significantly higher fluorescein diacetate (FDA) hydrolysis, alkaline phosphatase, polyphenol oxidase, cellulase, ß-glucosidase, and dehydrogenase activities were observed with plant debris treatment. High-throughput pyrosequencing showed that the number of total operational taxonomic units (OTUs) of bacteria estimated by using the Chao1 analysis was 2064 (in the control) and 1821 (with the plant debris treatment). The Shannon index, functional organization, and Venn diagrams revealed that the enriched OTUs in plant debris-treated community were less diversified than those in the control sample. The prominent bacterial phyla Firmicutes and Bacteroidetes were more diverse after plant debris addition. At the class level, the relative abundance of Alphaproteobacteria increased by 114% when plant debris was added, whereas the relative abundances of Beta-, Delta-, and Gammaproteobacteria decreased by 42, 78, and 86%, respectively. Azospirillum and Dechloromonas, the dominant phylogenetic groups at the genus level, increased with plant debris addition. Our study showed the importance of the above microbial genera in plant debris-mediated P retention in sediment.

19.
Medicine (Baltimore) ; 97(21): e10743, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29794752

RESUMO

With the improvement of living standard, gestational diabetes mellitus (GDM) incidence is increasing every year. We observed the effects of abnormal 75 g oral glucose tolerance test (OGTT) at different time points on neonatal complications and neurobehavioral development in GDM.A total of 144 newborns whose mothers were diagnosed with GDM and received prenatal examination and childbirth in our hospital from October 2015 to April 2016, were observed in this study. Pregnant women underwent 75 g OGTT and the blood glucose level was recorded on an empty stomach, as well as postprandial 1 and 2 hours, respectively. Based on the frequency of 75 g OGTT-abnormal time points, the pregnant women were divided into group 1 (OGTT abnormality at 1 time point), group 2 (OGTT abnormality at 2 time points), and group 3 (OGTT abnormality at 3 time points). Neonatal behavioral neurological assessment (NBNA) was performed on the 3 groups, respectively.In the total score of NBNA, there was a significant difference among the 3 groups (F = 17.120, P = .000), and there were significant differences between the 3 groups (all P < .05). The incidence of neonatal hypoglycemia was significantly lower in groups 1 and 2 than in group 3, and the incidence of macrosomia was significantly lower in groups 1 than in groups 2 and 3 (all P < .05). In the 144 newborns, NBNA scoring was significantly lower in the newborns with hypoglycemia than in the newborns with normal blood glucose level, and in macrosomia than in the newborns with normal body weight (all P < .01).With the increase of OGTT-abnormal time points in the pregnant women with GDM, the incidences of neonatal hypoglycemia and macrosomia rise and neonatal NBNA score decreases. Therefore, reasonable measures should be adopted as early as possible to prevent poor prognosis in the pregnant women with GDM.


Assuntos
Diabetes Gestacional/fisiopatologia , Macrossomia Fetal/epidemiologia , Intolerância à Glucose/complicações , Teste de Tolerância a Glucose/métodos , Hipoglicemia/epidemiologia , Adulto , Glicemia/análise , Desenvolvimento Infantil/fisiologia , Feminino , Humanos , Incidência , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Triagem Neonatal/métodos , Exame Neurológico/métodos , Gravidez
20.
Materials (Basel) ; 11(4)2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29642571

RESUMO

The reactive ion etching (RIE) process of fused silica is often accompanied by surface contamination, which seriously degrades the ultraviolet laser damage performance of the optics. In this study, we find that the contamination behavior on the fused silica surface is very sensitive to the RIE process which can be significantly optimized by changing the plasma generating conditions such as discharge mode, etchant gas and electrode material. Additionally, an optimized RIE process is proposed to thoroughly remove polishing-introduced contamination and efficiently prevent the introduction of other contamination during the etching process. The research demonstrates the feasibility of improving the damage performance of fused silica optics by using the RIE technique.

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