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1.
J Cardiothorac Surg ; 16(1): 307, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663408

RESUMO

BACKGROUND: Bronchiolar adenoma (BA) is a recently proposed diagnostic terminology, which is considered as the expansion of the concept of ciliated muconodular papillary tumors. BA is considered to be a benign neoplasm, but a few previous cases have been reported with the possibility of malignant transformation. Therefore, the genetic and histological nature of BA is controversial so far. We describe a rare case of multiple BAs with malignant transformation and CCNE1 (cyclin E1) mutation to increase the understanding of this disease. CASE DESCRIPTION: A 56-year-old woman was admitted to our hospital due to two ground-glass nodules (GGNs) in the left lung detected by chest CT without symptom. The pure GGN located in the upper lingual segment about 6 mm in diameter and another mixed GGN located in the dorsal segment about 7 mm. The two GGNs have been found a year ago without treatment, and the mixed GGN become larger to 8 mm with vacuole sign in the next year health checkup. We performed a wedge resection of the two nodules completely by video-assisted thoracoscopy (VATS). Postoperative pathology indicated that the pure GGN was atypical bronchial adenoma, while the mixed GGN was atypical bronchial adenoma with malignant transformation which was missed in frozen section. Gene mutations analysis by next-generation sequencing (NGS) showed CCNE1 gene mutation in both lesions, and her-2 mutation was identified in the mixed GGN. The programmed cell death 1 ligand 1 (PD-L1) expression analysis of tumor cells showed 0% and less than 1% in the pure GGN and the mixed GGN, respectively. CONCLUSION: BA is generally considered to be a benign tumor. The present study indicated that BA may be carcinogenic in atypical cases with some driver genes mutation and we should be vigilant for its potentiality of malignant transformation in clinical practice.

2.
Int J Environ Health Res ; : 1-11, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496690

RESUMO

We tested the hypothesis of whether maternal residential proximity to municipal solid waste incinerator (MSWI) sites could significantly affect birth outcomes. This retrospective birth cohort study conducted at the International Peace Maternity and Infant Hospital, Shanghai, China, included 59,606 mothers with singleton live births during 2014-2018. Multivariate generalized linear models were used to examine associations between residential proximity to MSWI sites and birth outcomes. Small for gestational age (SGA) was significantly more common among children with maternal residential proximity to MSWI sites (odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.07-1.34). Maternal prepregnancy body mass index (BMI) influenced this association. Infants of underweight mothers (prepregnancy BMI <18.5 kg/m2) with MSWI exposure (OR=2.00, 95% CI: 1.58-2.52) had higher risks of SGA than their counterparts. Our findings underscore the need to prevent adverse environmental effects of MSWI on birth outcomes; improved exposure assessment measures are warranted in future studies.

3.
Placenta ; 114: 100-107, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34509037

RESUMO

INTRODUCTION: In this study we examined the hypothesis that a hypoxic intrauterine environment causes mitochondrial dysfunction of trophoblasts in fetal growth restriction (FGR). METHODS: The mtDNA content, mRNA levels of mitochondrial encoded genes (ND6, COX I), mitochondrial membrane proteins (COX I, COX IV and VDAC), HIF-1α and BINP3 (mitophagy receptor) protein levels were examined in FGR placentas and normal placentas. The mitochondrial function (ATP production and mitochondrial membrane potential-ΔΨm) and above related proteins were further examined in hypoxic HTR-8/SVneo cells induced by cobalt chloride (CoCl2). Mitophagy and its regulating mechanism under hypoxia in FGR was also investigated. RESULTS: Compared with normal controls, both FGR placentas and CoCl2-treated trophoblast cells demonstrated statistically lower mtDNA content, reduced mRNAs of mitochondrial encoding genes, and decreased mitochondrial membrane proteins, accompanied by increased HIF-1α. Mitochondrial functions were impaired as demonstrated by decreased ATP production, and, reduced ΔΨm in CoCl2-treated cells. Meanwhile, mitophagy was markedly enhanced as indicated by increased LC3 fluorescent puncta in mitochondria of hypoxic trophoblastic cells. The upregulated BINP3 expression was demonstrated in FGR placentas as well as in hypoxic trophoblastic cells. DISCUSSION: We demonstrated that hypoxic conditions lead to impaired mitochondrial function in trophoblasts in FGR. Reduced mtDNA may be associated with enhanced mitophagy via activating HIF-1α/BINP3 signalling pathway, that may, in turn, affect nutrition and energy transfer to the growth-restricted fetus.

4.
J Med Chem ; 64(19): 14465-14476, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34549580

RESUMO

In this work, a series of novel substituted polycyclic pyridone derivatives were designed and synthesized as potent anti-influenza agents. The cytopathic effect (CPE) assay and cytotoxicity assay indicated that all of the compounds possessed potent anti-influenza virus activity and relatively low cytotoxicity; some of them inhibited the replication of influenza A virus (IAV) at picomolar concentrations. Further studies revealed that, at a concentration of 3 nM, three compounds (10a, 10d, and 10g) could significantly reduce the M2 RNA amounts and M2 protein expression of IAV and inhibit the activity of RNA-dependent RNA polymerase (RdRp). Among them, (R)-12-(5H-dibenzo[a,d][7]annulen-5-yl)-7-hydroxy-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione (10a) was found to be a promising anti-influenza drug candidate with good human liver microsomal stability, as well as with better selectivity index and oral bioavailability than Baloxavir.

5.
JAMA Netw Open ; 4(7): e2117409, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34279647

RESUMO

Importance: Bile acids play essential roles in metabolic modulation. Excessive serum total bile acid (sTBA) levels during pregnancy are associated with adverse perinatal outcomes; however, their association with the risk of intrauterine growth restriction (IUGR) remains unclear. Objective: To investigate the association between maternal sTBA concentration during pregnancy and the risk of IUGR. Design, Setting, and Participants: This retrospective cohort study included pregnant individuals who delivered live singleton neonates and had regular antenatal examination records available at a hospital-based center in Shanghai, China, from 2014 to 2018. Data were analyzed from July to November 2020. Exposures: Maternal sTBA concentration during pregnancy. Main Outcomes and Measures: Fetal birth weight and probability of low birth weight (LBW) and IUGR. Results: This study included 68 245 singleton pregnancies with live births for analysis. The mean (SD) age of the pregnant individuals was 30.5 (3.8) years, 67 168 patients (98.4%) were Han, and 50 155 (73.5%) were nulliparous. Nonlinear regression models suggested that there was an inverted J-shaped association between maternal sTBA level during pregnancy and fetal birth weight, with a steep decrease in birth weight at high sTBA levels (estimated mean [SE] birth weight for sTBA of 40.8 ug/mL, 2879 [39.9] g) and greater birth weights at lower sTBA levels (estimated mean [SE] birth weight for sTBA 0.4 µg/mL, 3290 [3.9] g; and for 4.1 µg/mL, 3334 [1.6] g). Lower birth weight and a higher incidence of IUGR were observed in patients with gestational hypercholanemia (sTBA ≥4.08 µg/mL) compared with those without gestational hypercholanemia (birth weight: estimated adjusted mean [SE], 3309 [3.32] vs 3338 [0.80] g; P = .005; incidence of IUGR: 62 of 4467 [1.4%] vs 312 of 63 778 [0.5%]; P < .001). Moreover, compared with patients with sTBA concentrations of less than 4.08 µg/mL, those with gestational hypercholanemia had an increased risk of LBW (adjusted odds ratio [aOR], 1.29; 95% CI, 1.09-1.53) and IUGR (aOR, 2.18; 95% CI, 1.62-2.91). In addition, there was an additive interaction between hypertensive disorders in pregnancy (HDP) and hypercholanemia on LBW and IUGR risk. The highest risks of LBW and IUGR were found in pregnant individuals with both HDP and hypercholanemia compared with those with normotensive pregnancies with sTBA concentrations less than 4.08 µg/mL (LBW: aOR, 9.13; 95% CI, 6.88-12.12; IUGR: aOR, 19.14; 95% CI, 12.09-30.28). Conclusions and Relevance: This study found that gestational hypercholanemia was associated with an increased risk of LBW and IUGR, especially in pregnant individuals with HDP. Therefore, it would be meaningful to monitor sTBA concentration during the follow-up of pregnancies with potential IUGR.

6.
J Cardiothorac Surg ; 16(1): 192, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233697

RESUMO

INTRODUCTION: Chondroblastoma is a rare, benign locally but aggressive bone tumor. It accounts for < 1% of primary bony tumors, and mostly arises from long bones; the rib chondroblastoma is especial rare. Due to its rarity, there are no definitive or standard treatment guidelines. CASE PRESENTATION: A case of a 24-year-old male with a chondroblastoma located on the 6th posterior left rib. Computed tomography (CT) demonstrated a rib tumor that was a well-defined oval lesion of 20 mm × 18 mm, with lytic bone destruction. The imaging first diagnosis was Langerhans cell histiocytosis (LCH), a giant cell tumor, or other type of neoplasm. The whole tumor and a part of partial rib were resected by video-assisted thoracoscopy surgery (VATS). Pathological and immunohistochemical (IHC) examination made a diagnosis of chondroblastoma. Compared with traditional open thoracic surgery, VATS can achieve the same effects and cause less injury to patient. No postoperative adjuvant therapy was given, and had followed up 23 months after surgery, there was no recurrence or metastasis. CONCLUSION: Chondroblastoma has a risk of recurrence and metastasis, surgery plays an important role in the treatment of chondroblastoma, VATS can achieve the same outcome as traditional open thoracic surgery with less pain and lung function. Close follow-up is needed postoperative.


Assuntos
Neoplasias Ósseas/cirurgia , Condroblastoma/cirurgia , Cirurgia Torácica Vídeoassistida , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Condroblastoma/diagnóstico por imagem , Condroblastoma/patologia , Humanos , Masculino , Recidiva Local de Neoplasia , Radiografia Torácica , Costelas , Tomografia Computadorizada por Raios X , Adulto Jovem
7.
Bioorg Chem ; 114: 105026, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34186467

RESUMO

In this work, two series of cyclic amine-containing benzimidazole carboxamide derivatives were designed and synthesized as potent anticancer agents. PARP1/2 inhibitory activity assays indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was investigated against four human cancer cell lines (MDA-MB-436, MDA-MB-231, MCF-7 and CAPAN-1), and several compounds exhibited strong cytotoxicity to tumor cells. Among them, 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[d]imidazole-4-carboxamide (17d) was found to be effective PARP1/2 inhibitors (IC50 = 4.30 and 1.58 nM, respectively). In addition, 17d possessed obvious selective antineoplastic activity and noteworthy microsomal metabolic stability. What's more, further studies revealed that 17d was endowed with an excellent ADME profile. These combined results indicated that 17d could be a promising candidate for the treatment of cancer.

8.
Medicine (Baltimore) ; 100(26): e26449, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190169

RESUMO

RATIONALE: Anaplastic lymphoma kinase (ALK) inhibitors have been approved for patients with ALK-rearrangement lung cancer. The effect is superior to the standard first-line therapy of pemetrexed plus platinum-based chemotherapy. However, ALK inhibitors are associated with rare and sometimes fatal adverse events. Organizing pneumonitis (OP) is a rare and serious adverse event usually caused by ceritinib, and it is easily misdiagnosed as infectious pneumonia, metastasis, or cancer progression. PATIENT CONCERNS: A 56-year-old female presented with chest tightness and dyspnea for more than 10 days. She was previously healthy with no significant medical history. Workup including chest computed tomography (CT), pathological examination of a biopsy specimen, and next-generation sequencing was consistent with a diagnosis of IVA ALK-rearrangement lung adenocarcinoma. She was treated with pemetrexed plus platinum-based chemotherapy and crizotinib concurrently, followed by maintenance therapy with crizotinib alone and she had an almost complete response. However, about 26 months after beginning treatment she developed multiple brain metastases. Crizotinib was discontinued and she was begun on ceritinib. After about 3 months the brain metastases had almost complete response. After 5 months of ceritinib, however, multiple patchy lesions appeared in the bilateral upper lungs. DIAGNOSES: Treatment with antibiotics had no effect and blood and sputum cultures are negative. A CT-guided biopsy of the upper lung was performed, and pathological hematoxylin-eosin staining and immunohistochemical studies were consistent with OP. INTERVENTIONS: Ceritinib was discontinued, she was begun on prednisone 0.5 mg/kg orally every day, and regular follow-up is necessary. OUTCOMES: CT of the chest 2 and 4 weeks after beginning prednisone showed the lung lesions to be gradually resolving, and she was continued on prednisone for 2 months and gradually reduced the dose of prednisone every 2 weeks. No related adverse events were occurred in patient. LESSONS: OP must be differentiated from infectious pneumonia, metastasis, or cancer progression. The mechanism of OP is still unknown and needs further research. Biopsy plays a role in making a diagnosis of OP. In our patient, discontinuing ceritinib and treating her with prednisone resulted in a good outcome.


Assuntos
Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Pneumonia em Organização Criptogênica , Neoplasias Pulmonares , Prednisona/administração & dosagem , Pirimidinas , Sulfonas , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/fisiopatologia , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética , Antineoplásicos/uso terapêutico , Biópsia/métodos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Crizotinibe/uso terapêutico , Pneumonia em Organização Criptogênica/induzido quimicamente , Pneumonia em Organização Criptogênica/patologia , Pneumonia em Organização Criptogênica/terapia , Substituição de Medicamentos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Pessoa de Meia-Idade , Pemetrexede/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonas/administração & dosagem , Sulfonas/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
9.
Electrophoresis ; 42(16): 1578-1593, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34018209

RESUMO

The Y-STR landscape of Coastal Southeastern Han (CSEH) living in Chinese southeast areas (including Guangdong, Fujian, and Zhejiang provinces) is still unclear. We investigated 62 Y-STR markers in a reasonably large number of 1021 unrelated males and 1027 DNA-confirmed father-son pairs to broaden the genetic backgrounds of CSEH. In total, 85 null alleles, 121 off-ladder alleles, and 95 copy number variants were observed, and 1012 distinct haplotypes were determined with the overall HD and DC values of 0.999974 and 0.9912. We observed 369 mutations in 76 099 meiotic transfers, and the average estimated Y-STR mutation rate was 4.85 × 10-3 (95% CI, 4.4 × 10-3 -5.4 × 10-3 ). The Spearman correlation analyses indicated that GD values (R2 = 0.6548) and average allele sizes (R2 = 0.5989) have positive correlations with Y-STR mutation rates. Our RM Y-STR set including 8 candidate RM Y-STRs, of which DYS534, DYS630, and DYS713 are new candidates in CSEH, distinguished 18.52% of father-son pairs. This study also clarified the population structures of CSEH which isolated in population-mixed South China relatively. The strategy, SM Y-STRs for familial searching and RM Y-STRs for individual identification regionally, could be applicable based on enough knowledge of the Y-STR mutability of different populations.

10.
BMJ Open ; 11(4): e045192, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795307

RESUMO

INTRODUCTION: Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk. METHODS AND ANALYSIS: This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study. ETHICS AND DISSEMINATION: The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie-CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation. TRIAL REGISTRATION NUMBER: ChiCTR1800017773. PROTOCOL VERSION: November 11, 2020 (Version #5).


Assuntos
Obesidade Pediátrica , Canadá , Criança , Pré-Escolar , China , Feminino , Humanos , Masculino , Relações Mãe-Filho , Estudos Multicêntricos como Assunto , Obesidade Pediátrica/prevenção & controle , Projetos Piloto , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
J Agric Food Chem ; 69(6): 1916-1924, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33541074

RESUMO

Indole-3-acetic acid (IAA) is a critical plant hormone that regulates cell division, development, and metabolism. IAA synthesis in plants and plant-associated microorganisms cannot fulfill the requirement for large-scale agricultural production. Here, two novel IAA biosynthesis pathways, tryptamine (TAM) and indole-3-acetamide (IAM), were developed for IAA production by whole-cell catalysis and de novo biosynthesis in an engineered Escherichia coli MG1655. When 10 g/L l-tryptophan was used as a substrate, an MIA-6 strain containing a heterologous IAM pathway had the highest IAA titer of 7.10 g/L (1.34 × 103 mg/g DCW), which was 98.4 times more than MTAI-5 containing the TAM pathway by whole-cell catalysis. De novo IAA biosynthesis was optimized by improving NAD(P)H availability, resulting in an increased IAA titer of 906 mg/L obtained by the MGΔadhE::icd strain, which is 29.7% higher than the control. These strategies exhibit the potential for IAA production in engineered E. coli and possible industrial applications.


Assuntos
Escherichia coli , Ácidos Indolacéticos , Escherichia coli/genética , Reguladores de Crescimento de Plantas , Plantas , Triptofano
12.
Forensic Sci Int ; 321: 110720, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33639416

RESUMO

In the field of drowning research, the method of diatom morphology has been most applied to determine whether the cause of death is drowning. However, the characteristics of complex operation, high level of professional knowledge drive us to propose a new method. Here, based on the common phytoplankton in water(such as diatoms and Aeromonas), aiming at the rbcL, 23 S, NIES, rPOD, Hly and preprotoxin aerolysin gene, we designed 6 pairs of specific primers and applied SYBR Green real-time qPCR(RT-qPCR) method to detect phytoplankton in the Pearl River Basin of Guangdong Province, China, so as to achieve the purpose of diagnosing drowning. After the experimental verification of the corresponding algae species and the standard strains of bacteria, as well as the verification of tissue samples (lung, liver and kidney) of 56 cases( 40 drowning cases and 16 non-drowning cases), we found that these primers were of great accuracy and tedious laboratory work of diatom test was reduced. Based on the advantages of high throughput, short period and high sensitivity, this RT-qPCR method is expected to diagnose drowning more rapidly and accurately.


Assuntos
Aeromonas/genética , Cianobactérias/genética , Primers do DNA , Diatomáceas/genética , Afogamento/diagnóstico , Benzotiazóis , Diaminas , Corantes Fluorescentes , Humanos , Rim/patologia , Fígado/patologia , Pulmão/patologia , Quinolinas , Reação em Cadeia da Polimerase em Tempo Real
13.
Int J Legal Med ; 135(2): 443-444, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32030456

RESUMO

The genetic polymorphism of 17 autosomal short tandem repeat (STR) loci included in the PowerPlex® 18D System was evaluated from 638 unrelated healthy Han individuals of Meizhou in Guangdong Province, Southern China. The values of combined power of discrimination (CPD) and the combined probability of exclusion (CPE) were observed as 0.999999999999999 and 0.999999933. Penta E showed the highest values of polymorphism information content (0.9073), expected heterozygosity (0.9147), and observed heterozygosity (0.9373), whereas TPOX showed the lowest (0.5373, 0.6035, and 0.6082). Furthermore, both of the PCA plot and neighbor-joining phylogenetic tree showed that the Meizhou Hakka population has a relatively close genetic relationship with the Guangdong Han population. The results showed that most of these 17 autosomal STR loci were highly informative and can be effective for forensic individual identification and paternity testing in Meizhou Hakka population.

14.
Mol Med Rep ; 22(6): 5069-5082, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174040

RESUMO

Long non­coding RNAs (lncRNAs) affect atherosclerosis by regulating the physiological and pathological processes of endothelial cells; however, the role of lncRNA WEE2 antisense RNA 1 (WEE2­AS1) in arteriosclerosis obliterans (ASO) is not completely understood. The present study aimed to explore the function of lncRNA WEE2­AS1 in human vascular endothelial cells. The results indicated that lncRNA WEE2­AS1 was significantly elevated in plasma and artery tissue samples of patients with ASO compared with healthy controls. The fluorescence in situ hybridization results suggested that lncRNA WEE2­AS1 was expressed in the cytoplasm and nuclei of primary human umbilical vein endothelial cells (HUVECs). The Cell Counting Kit­8 assay results suggested that lncRNA WEE2­AS1 knockdown significantly promoted HUVEC viability, whereas lncRNA WEE2­AS1 overexpression inhibited HUVEC viability compared with the negative control groups. Furthermore, analysis of the cell cycle by flow cytometry indicated that lncRNA WEE2­AS1 knockdown significantly decreased the proportion of cells in the G0/G1 phase and significantly increased the proportion of cells in the G2/M phase compared with the negative control group. However, lncRNA WEE2­AS1 overexpression had no significant effect on cell cycle distribution compared with the negative control group. The western blotting results indicated that lncRNA WEE2­AS1 knockdown significantly reduced the expression levels of phosphorylated cyclin dependent kinase 1, WEE1 homolog 2 and myelin transcription factor 1, but increased the expression level of cell division cycle 25B compared with the negative control group. lncRNA WEE2­AS1 overexpression displayed the opposite effect on protein expression. Collectively, the present study suggested that lncRNA WEE2­AS1 was significantly upregulated in ASO and may serve a role in regulating human vascular endothelial cell viability. Further investigation into lncRNA WEE2­AS1 may broaden the current understanding of the molecular mechanism underlying ASO, and aid with the identification of specific probes and precise targeted drugs for the diagnosis and treatment of ASO.


Assuntos
Arteriosclerose Obliterante/genética , Proteínas de Ciclo Celular/genética , Células Endoteliais/metabolismo , Proteínas Tirosina Quinases/genética , Idoso , Arteriosclerose Obliterante/metabolismo , Proteína Quinase CDC2/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/fisiologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/metabolismo , RNA Antissenso/genética , RNA Longo não Codificante/genética
15.
Mediators Inflamm ; 2020: 3691701, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33223955

RESUMO

Recent studies have illuminated that blocking Ca2+ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.

16.
Sensors (Basel) ; 20(19)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007834

RESUMO

Graphene is a new type of carbon material with a flexible, two-dimensional structure. Due to the excellent stability of its lattice structure and its mechanical flexibility, graphene-based materials can be applied in flexible humidity sensors. At present, the application of graphene-based flexible humidity sensors in the fields of medical care and environmental monitoring is attracting widespread attention. In this review, the basic properties of graphene oxide (GO) and reduced graphene oxide (rGO) as moisture-sensitive materials and methods for their preparation were introduced. Moreover, three methods for improving the performance of moisture-sensitive materials were discussed. The working principle of different types of graphene-based humidity sensors were introduced. The progress in the research on graphene-based flexible humidity sensors in four respects: Human respiration, skin moisture, human sweat, and environmental humidity were discussed. Finally, the future research, following the development trends and challenges, to develop the potential of integrated, graphene-based flexible humidity sensors were discussed.

17.
Appl Microbiol Biotechnol ; 104(23): 10005-10018, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33128613

RESUMO

L-Tyrosine is a versatile compound used in the fine chemical, pharmaceutical, and functional food industries. Here, we report a bi-enzymatic cascade involving alanine racemase (ALR) and D-amino acid oxidase (DAAO) to produce pyruvate, as co-substrate for L-tyrosine production, from the cheap substrate L-alanine. The BpALR (ALR from Bacillus pseudofirmus) was used as a whole-cell biocatalyst, converting L-alanine to D, L-alanine. The FsDAAO (DAAO from Fusarium solani) was immobilized to oxidize the D-alanine generated in the first step to pyruvate. Both systems were combined as a continuous-flow reactor for maximized L-alanine-to-pyruvate conversion rates. The optimal parameters and appropriate conditions for FsDAAO immobilization were investigated. The pyruvate concentration of 86.6 g/L was achieved within 17 h. Subsequently, a whole-cell biocatalyst system for L-tyrosine production, catalyzed by the tyrosine phenol-lyase (TPL) from Erwinia herbicola (EhTPL), was developed, and a fed-batch approach was applied with phenol and the pyruvate produced with the ALR/DAAO system mentioned above. The concentration of phenol and pyruvate in the reactor should not exceed 7.5 g/L and 10 g/L, respectively. Significantly, the L-tyrosine concentration of 152.5 g/L was achieved within 10 h, demonstrating the great potential for high-efficiency production of L-tyrosine through the approach we established in this paper. Graphical abstract KEY POINTS: • A specific bioreactor system for pyruvate produced from l-alanine was developed • The appropriate condition for immobilization of FsDAAO was investigated • A fed-batch process was established to produce l-tyrosine with recombinant E. coli • The bi-enzymatic cascade was successfully used for l-tyrosine production at low cost.


Assuntos
Tirosina Fenol-Liase , Tirosina , Bacillus , Escherichia coli/genética , Fusarium , Ácido Pirúvico , Tirosina Fenol-Liase/genética
18.
Placenta ; 99: 173-179, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32810765

RESUMO

INTRODUCTION: The aim of this research was to study the alteration of three key tight junction proteins, to explore whether they were involved in the occurrence of prelabor rupture of the membrane (PROM) and to determine the correlation with intrauterine infection. METHODS: A total of 208 women were enrolled between January 2015 to December 2018, including those with preterm and term PROM (PROM group) and normal pregnancies with intact fetal membrane (control group). We investigated the expressions of three key TJ molecules (Zonula occludens-1, Occludin and Claudin-5) in fetal membranes. The localization and expression of Zonula occludens-1 (ZO-1) in the amnion and chorion were studied by immunohistochemistry assay. The associations between ZO-1 expression levels and extent of inflammatory reactions as well as other obstetric characteristics were further studied using Spearman's rank correlation test and Mann-Whitney U test. RESULTS: ZO-1 was significantly downregulated in PROM group compared with control group (P < 0.001), whereas no significant changes were found for Occludin and Claudin-5. ZO-1 expression was reduced in the chorion and amnion layers in PROM group compared with that in control group, which showed a significant difference (P < 0.01), but no significant differences were observed between the preterm PROM and term PROM groups (P > 0.05). The expression levels of ZO-1 in the chorion were negatively correlated with the stage/grade of acute chorioamnionitis (P < 0.05). DISCUSSION: Our study suggests that inflammation-related downregulation of ZO-1 might be a pivotal event in the occurrence of PROM, which helps to clarify the mechanism of membrane rupture caused by infection.

19.
Sensors (Basel) ; 20(13)2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32635285

RESUMO

Pine wilt disease (PWD) caused by pine wood nematode (PWN, Bursaphelenchus xylophilus) originated in North America and has since spread to Asia and Europe. PWN is currently a quarantine object in 52 countries. In recent years, pine wilt disease has caused considerable economic losses to the pine forest production industry in China, as it is difficult to control. Thus, one of the key strategies for controlling pine wilt disease is to identify epidemic points as early as possible. The use of hyperspectral cameras mounted on drones is expected to enable PWD monitoring over large areas of forest, and hyperspectral images can reflect different stages of PWD. The trend of applying hyperspectral techniques to the monitoring of pine wilt disease is analyzed, and the corresponding strategies to address the existing technical problems are proposed, such as data collection of early warning stages, needs of using unmanned aerial vehicles (UAVs), and establishment of models after preprocessing.


Assuntos
Pinus/parasitologia , Doenças das Plantas/parasitologia , Tylenchida/patogenicidade , Animais , China
20.
J Cell Physiol ; 235(12): 9538-9556, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32529639

RESUMO

Despite the high prevalence of varicose veins, the underlying pathogenesis of this disease remains unclear. The present study aims to explore the role of insulin-like growth factor binding protein 6 (IGFBP6) in vascular smooth muscle cells (VSMCs). Using a protein array approach, we identified several differentially expressed proteins between varicose great saphenous veins and normal great saphenous veins. Bioinformatic analysis showed that IGFBP6 was closely related to cell proliferation. Further validation confirmed that IGFBP6 was one of the most highly expressed proteins in varicose vein tissue. Knocking down IGFBP6 in VSMCs significantly attenuated cell proliferation and induced the S phase arrest during the cell cycle. Further experiments demonstrated that IGFBP6 knockdown increased cyclin E ubiquitination, which reduced expression of cyclin E and phosphorylation of CDK2. Furthermore, IGFBP6 knockdown arrested centrosome replication, which subsequently influenced VSMC morphology. Ultimately, IGFBP6 was validated to be involved in VSMC proliferation in varicose vein tissues. The present study reveals that IGFBP6 is closely correlated with VSMC biological function and provides unprecedented insights into the underlying pathogenesis of varicose veins.


Assuntos
Ciclina E/genética , Quinase 2 Dependente de Ciclina/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Proteoma/genética , Proliferação de Células/genética , Feminino , Regulação da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Análise Serial de Proteínas , Veia Safena/metabolismo , Varizes/metabolismo , Varizes/patologia
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