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1.
Eur J Pediatr ; 183(4): 1741-1750, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38233605

RESUMO

Differences in clinical characteristics of early-onset and late-onset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in neonates remain unclear. This study aimed to determine whether there are differences in the main clinical, radiological, and laboratory features of early-onset and late-onset SARS-CoV-2 infections in neonates. This single-center, prospective cohort study enrolled neonates with SARS-CoV-2 infection from December 7, 2022, to January 3, 2023, and evaluated their clinical characteristics during hospitalization. All neonates (N = 58) infected with SARS-CoV-2 within 28 days of birth who were admitted to the neonatal intensive care unit of Taizhou Hospital were included. These neonates were classified into the early-onset (diagnosed within 7 days of birth) and late-onset (diagnosed more than 7 days after birth) groups. The symptoms, treatment, and prognosis of SARS-CoV-2 infection were the main study outcomes. The incidence of hospitalization attributable to SARS-CoV-2 infection was 10.6% (58 of 546 neonates) in Linhai. Sixteen (28%) of the 58 SARS-CoV-2 infections were early-onset cases, and 42 (72%) were late-onset cases. The common symptoms among the late-onset group were fever (p < 0.001) and cough (p < 0.001). Neonates with late-onset SARS-CoV-2 infection (p < 0.001) were significantly more likely to develop pneumonia.  Conclusion: The clinical symptoms and rates of pneumonia caused by SARS-CoV-2 infection in neonates differed between the early-onset and late-onset groups. Different clinical management is necessary for neonates with early-onset and late-onset SARS-CoV-2 infections. What is Known: • Neonates are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). • Differences in clinical characteristics of early-onset and late-onset SARS-CoV-2 infections in neonates remain unclear. What is New: • Fever and cough were the most common symptoms among neonates with late-onset infection. • Neonates with late-onset SARS-CoV-2 infection were more likely to develop pneumonia.


Assuntos
COVID-19 , Pneumonia , Complicações Infecciosas na Gravidez , Recém-Nascido , Humanos , Gravidez , Feminino , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Prospectivos , Tosse , Febre/etiologia , Complicações Infecciosas na Gravidez/diagnóstico
2.
Inorg Chem ; 60(24): 19263-19269, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34817992

RESUMO

Incorporating heterometal and chromogenic groups into the titanium oxo cluster (TOC) nanomaterials is one of the effective strategies for the development of new high-performance photoelectrically active materials. In this Article, we report the structures and photoelectrochemical (PEC) performances of a family of TOCs, including pure [Ti12O8(OEt)16L8] ({Me-Ti12}) and six Cd-doped clusters formulated as [H4Cd2Ti10O8(OEt)16(L)8(H2O)2] ({Cd2Ti10}; L = salicylic acid and their derivatives). The six Cd-doped clusters are isostructural, containing the same {Cd2Ti10O8} core, but are protected by salicylic ligands modified with different functional groups. The compositions, structures, and solution stability of these clusters have been studied in detail by single-crystal X-ray diffraction and electrospray ionization mass spectrometry measurements. The embedding of heterometallic Cd(II) and chemical modification of organic protective shells can effectively regulate the PEC water oxidation activity of those clusters, with {F-Cd2Ti10} having the highest turnover number of 518.55 and the highest turnover frequency of 172.85 h-1. Our work highlights the potential of using TOCs that do not contain noble metals as water oxidation catalysts, and their catalytic activity can be regulated by structural modification.

3.
Biol Pharm Bull ; 38(6): 935-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25810454

RESUMO

The ubiquitin-proteasome pathway plays an important role in regulating apoptosis and the cell cycle. Recently, proteasome inhibitors have been shown to have antitumor effects and have been used in anticancer therapy for several cancers such as multiple myeloma. Although some flavones, such as apigenin, chrysin and luteolin, have a specific role in the inhibition of proteasome activity and induced apoptosis in some reports, these findings did not address all flavone types. To further investigate the proteasome-inhibitory mechanism of flavonoids, we examined the inhibitory activity of 5,6,7-trihydroxyflavone, baicalein and 5,6,7,4'-tetrahydroxyflavone, scutellarein on extracted proteasomes from mice and cancer cells. Unlike the other flavones, baicalein and scutellarein did not inhibit proteasome activity or accumulate levels of ubiquitinated proteins. These results indicate that flavones with hydroxy groups at positions 5, 6 and 7 of the A-ring lack the anti-proteasome function.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos/farmacologia , Flavonas/farmacologia , Neoplasias/metabolismo , Extratos Vegetais/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos Fitogênicos/química , Apigenina/química , Apigenina/farmacologia , Apoptose , Flavanonas/química , Flavanonas/farmacologia , Flavonas/química , Células HCT116 , Humanos , Células Jurkat , Estrutura Molecular , Fitoterapia , Extratos Vegetais/química , Inibidores de Proteassoma/química , Coelhos , Relação Estrutura-Atividade
4.
J Pediatr Surg ; 59(6): 1128-1134, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38368195

RESUMO

BACKGROUND: Sclerotherapy is purportedly less effective in patients with hemorrhagic than with non-hemorrhagic lymphatic malformations (LMs). We aimed to compare the efficacy of bleomycin-lauromacrogol foam (BLF) sclerotherapy in the treatment of macrocystic LMs with and without intralesional hemorrhage. METHODS: Fifty-five children with macrocystic LMs admitted to the Pediatric Surgery Department were retrospectively included. The patients were allocated into a hemorrhage group (23 cases) or a non-hemorrhage group (32 cases) based on the occurrence of an intracapsular hemorrhage. The diagnosis was confirmed by physical examination, color ultrasound, magnetic resonance imaging, and puncture findings. BLF was injected into the capsule after draining the cystic fluid under color ultrasound guidance. Patients whose lesions were unchanged or showed minor change after 1 month were treated again using the same method. Changes in lesion size and the number of treatments were recorded. Effectiveness was classified as excellent (volume reduction ≥90%), good (50%≤volume reduction<90%), or poor (volume reduction <50%). RESULTS: In the hemorrhage group, 17, 6, and 0 patients' outcomes were classified as excellent, good, and poor, respectively. The overall efficacy rate was 100%. In the non-hemorrhage group, 23, 7, and 2 patients' outcomes were classified as excellent, good, and poor, respectively. The overall efficacy rate was 93.8%. There was no significant difference in efficacy rate between groups (P = 0.767). CONCLUSIONS: BLF is an effective and safe treatment for macrocystic LMs with bleeding. The results were similar in patients with and without bleeding. LEVEL OF EVIDENCE: Treatment, Level III.


Assuntos
Bleomicina , Hemorragia , Anormalidades Linfáticas , Soluções Esclerosantes , Escleroterapia , Humanos , Escleroterapia/métodos , Masculino , Feminino , Estudos Retrospectivos , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Anormalidades Linfáticas/tratamento farmacológico , Anormalidades Linfáticas/terapia , Pré-Escolar , Hemorragia/etiologia , Criança , Soluções Esclerosantes/administração & dosagem , Soluções Esclerosantes/uso terapêutico , Lactente , Resultado do Tratamento , Polidocanol/administração & dosagem , Polidocanol/uso terapêutico , Adolescente , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico
5.
Phytother Res ; 27(9): 1362-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23147714

RESUMO

Baicalin and scutellarin are the major active principal flavonoids extracted from the Chinese herbal medicines Scutellaria baicalensis and Erigeron breviscapus (Vant.) Hand-Mazz. It has recently been reported that baicalin and scutellarin have antitumor activity. However, the mechanisms of action are unknown. We previously reported that some flavonoids have a specific role in the inhibition of the activity of proteasome subunits and induced apoptosis in tumor cells. To further investigate these pharmacological effects, we examined the inhibitory activity of baicalin and scutellarin on the extracted proteasomes from mice and cancer cells. Using fluorogenic substrates for proteasome catalytic subunits, we found that baicalin and scutellarin specifically inhibited chymotrypsin-like activity but did not inhibit trypsin-like and peptidyl-glutamyl peptide hydrolyzing activities. These data suggested that baicalin and scutellarin specifically inhibit chymotrypsin-like catalytic activity in the proteasome.


Assuntos
Apigenina/farmacologia , Quimotripsina/antagonistas & inibidores , Flavonoides/farmacologia , Glucuronatos/farmacologia , Inibidores de Proteassoma/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular , Erigeron/química , Feminino , Humanos , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos ICR , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Scutellaria baicalensis/química
6.
Dev Comp Immunol ; 145: 104726, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37149238

RESUMO

Piscidins participate in the innate immune response of fish, which aims to eliminate recognized foreign microbes and restore the homeostasis of immune system. We characterized two piscidin-like antimicrobial peptides (LjPL-3 and LjPL-2) isolated from Japanese sea bass (Lateolabrax japonicus). LjPL-3 and LjPL-2 showed different expression patterns in tissues. After Vibrio harveyi infection, the mRNA expression of LjPL-3 and LjPL-2 was upregulated in the liver, spleen, head kidney, and trunk kidney. The synthetic mature peptides LjPL-3 and LjPL-2 exhibited different antimicrobial spectra. Furthermore, LjPL-3 and LjPL-2 treatments decreased inflammatory cytokine production while promoting chemotaxis and phagocytosis in monocytes/macrophages (MO/MФ). LjPL-2, but not LjPL-3, displayed bacterial killing capability in MO/MФ. LjPL-3 and LjPL-2 administration increased Japanese sea bass survival after V. harveyi challenge, which was accompanied by a decline in bacterial burden. These data suggested that LjPL-3 and LjPL-2 participate in immune response through direct bacterial killing and MO/MФ activation.


Assuntos
Anti-Infecciosos , Bass , Doenças dos Peixes , Vibrioses , Animais , Monócitos , Macrófagos , Bass/metabolismo , Peptídeos Antimicrobianos , Proteínas de Peixes/metabolismo
7.
Huan Jing Ke Xue ; 44(7): 3997-4005, 2023 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-37438298

RESUMO

Microplastics (MPs), as a new type of pollutant, are widely detected in sewage treatment plants. Currently, research on MPs in traditional sewage treatment systems has mainly been focused on the pollution level and distribution characteristics, with a lack of studying the impact of MPs on the sludge granulation. In order to explore the effect of MPs on the granulation process, a microplastic exposure test was conducted by adding polyethylene terephthalate microplastics (PET-MPs), which are widespread in the environment. The operating performance of the system, extracellular polymeric substance (EPS) composition, and flora enrichment were analyzed on the sludge granulation. The results showed that the exposure of PET-MPs significantly accelerated the sludge granulation process, whereas the increase in EPS content dominated by PN enhanced the sludge surface hydrophobicity; the granulation rate and EPS secretion were proportional to the exposed particle size. Microplastics and EPS secretions synergistically promoted the formation of granular sludge. However, continuous microplastic exposure led to deterioration of the system decontamination performance and inhibited the degradation process of pollutants, with the most negative effect of nitrite nitrogen accumulation under 250 µm PET-MPs exposure, as high as (5.08±0.24) mg·L-1. The high-throughput sequencing revealed that the microbial community diversity fell in the experimental group. The dominant bacteria at the phylum level were Proteobacteria and Bacteroidota on the sludge granulation. Rhodocyclaceae, Sphingomonadaceae, Flavobacteriaceae, and Rhodanobacteraceae promoted flocculation by increasing EPS secretion. The decrease in Comamonadaceae and Chitinophagaceae weakened the ammonia and nitrite oxidation capacity of the system, whereas the decrease in Rhodobacteraceae, Hyphomonadaceae, and Xanthomonadaceae inhibited the removal of nitrate nitrogen.


Assuntos
Poluentes Ambientais , Matriz Extracelular de Substâncias Poliméricas , Microplásticos , Plásticos , Esgotos , Bacteroidetes , Nitrogênio
8.
Biochem Biophys Res Commun ; 417(1): 601-6, 2012 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-22182413

RESUMO

The retinoblastoma (Rb) tumor suppressor encodes a nuclear phosphoprotein that regulates cellular proliferation, apoptosis and differentiation. In order to adapt itself to these biological functions, Rb is subjected to modification cycle, phosphorylation and dephosphorylation. To directly determine the effect of phosphorylation-resistant Rb on liver development and function, we generated transgenic mice expressing phosphorylation-resistant human mutant Rb (mt-Rb) under the control of the rat hepatocyte nuclear factor-1 gene promoter/enhancer. Expression of mt-Rb in the liver resulted in macroscopic neoplastic nodules (adenomas) with ∼50% incidence within 15 months old. Interestingly, quantitative reverse transcriptase-PCR analysis showed that c-Myc was up-regulated in the liver of mt-Rb transgenic mice irrespective of having tumor tissues or no tumor. In tumor tissues, several c-Myc target genes, Foxm1, c-Jun, c-Fos, Bmi1 and Skp2, were also up-regulated dramatically. We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter. Our results suggest that continued upregulation of c-Myc target genes promotes the liver tumor formation after about 1 year of age.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteína do Retinoblastoma/metabolismo , Animais , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/genética , Humanos , Camundongos , Camundongos Transgênicos , Proteínas Nucleares/genética , Complexo Repressor Polycomb 1 , Proteínas Proto-Oncogênicas/genética , Ratos , Proteínas Repressoras/genética , Proteína do Retinoblastoma/genética , Regulação para Cima
9.
Front Pediatr ; 10: 1073711, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36683823

RESUMO

Background: Childhood obesity is a worldwide critical health concern. We aimed to clarify whether eating behaviours increased the risk of childhood obesity. Methods: We recruited 2,049 pre-school children aged 3-6 years between 1 December 2021 and 31 January 2022 in Taizhou, China. Children's weight status was classified according to the International Obesity Task Force criteria, and their eating behaviours were evaluated using the Children's Eating Behaviour Questionnaire. Correlation analyses, linear regressions, and one-way ANCOVA. were performed to analyse the association between children's eating behaviours and weight status. Results: In 'Food Avoidant' subscales, the scores of satiety responsiveness (P < 0.001) and slowness in eating (P = 0.001) were negatively associated with body mass index z score among pre-school children of both sexes. In 'Food Approach' subscales, the score of enjoyment of food was positively associated with body mass index z score in both boys (P = 0.007) and girls (P = 0.035), but the association of scores of food responsiveness with body mass index z score was found only in girls (P = 0.001). Conclusion: Our results supported that pre-school children with low scores in 'Food Avoidant' subscales and high scores in 'Food Approach' scales were more likely to become obese.

10.
J Sci Food Agric ; 91(13): 2443-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21626510

RESUMO

BACKGROUND: Momordica charantia (MC) is used in many Asian countries as a traditional functional food and medicine. Polypeptide-P, a 166 amino acid (AA) polypeptide isolated from MC seeds, has been reported to show hypoglycaemic effects in patients with type I or type II diabetes. The AA sequence of this peptide has been determined, but its gene sequence has yet to be published. RESULTS: In this study a gene-cloning strategy was employed to obtain the polypeptide-P gene sequence using degenerate reverse transcription polymer chain reaction and genome-walking methods. A complete 498 bp sequence encoding the polypeptide-P protein was cloned from MC seeds. Subsequent assays of the bioactivity of the expressed recombinant protein revealed that it had significant hypoglycaemic activity in alloxan-induced diabetic mice. This result suggests that recombinant polypeptide-P has hypoglycaemic effects. CONCLUSION: This is the first report of cloning and expression of the MC polypeptide-P gene. The cloned gene could be helpful for exploring the mechanisms of polypeptide-P gene expression and regulation in MC. Furthermore, this gene could be used as a potential tool both for screening MC varieties with high hypoglycaemically active substance content and for breeding new varieties of MC with high economic value, which could in turn be beneficial to farmers.


Assuntos
Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Momordica charantia/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Proteínas de Plantas/biossíntese , Proteínas de Plantas/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Diabetes Mellitus Experimental/tratamento farmacológico , Frutas/metabolismo , Genoma de Planta , Hipoglicemiantes/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Peso Molecular , Momordica charantia/genética , Peptídeos/genética , Peptídeos/uso terapêutico , Proteínas de Plantas/genética , Proteínas de Plantas/uso terapêutico , Distribuição Aleatória , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico
11.
Neural Regen Res ; 16(11): 2269-2275, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33818512

RESUMO

Somatosensory evoked potentials (SEPs) have been widely used to assess neurological function in clinical practice. A good understanding of the association between SEP signals and neurological function is helpful for precise diagnosis of impairment location. Previous studies on SEPs have been reported in animal models. However, few studies have reported the relationships between SEP waveforms in animals and those in humans. In this study, we collected normal SEP waveforms and decomposed them into specific time-frequency components (TFCs). Our results showed three stable TFC distribution regions in intact goats and rats and in humans. After we induced spinal cord injury in the animal models, a greater number of small TFC distribution regions were observed in the injured goat and rat groups than in the normal group. Moreover, there were significant correlations (P < 0.05) and linear relationships between the main SEP TFCs of the human group and those of the goat and rat groups. A stable TFC distribution of SEP components was observed in the human, goat and rat groups, and the TFC distribution modes were similar between the three groups. Results in various animal models in this study could be translated to future clinical studies based on SEP TFC analysis. Human studies were approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (approval No. UM 05-312 T/975) on December 5, 2005. Rat experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of Li Ka Shing Faculty of Medicine of the University of Hong Kong (approval No. CULART 2912-12) on January 28, 2013. Goat experiments were approved by the Animal Ethics Committee of Affiliated Hospital of Guangdong Medical University (approval No. GDY2002132) on March 5, 2018.

12.
Clin Endocrinol (Oxf) ; 72(3): 312-9, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19508587

RESUMO

OBJECTIVE: P450c17 deficiency (17alpha-hydroxylase/17,20-lyase deficiency, 17OHD) is a rare form of congenital adrenal hyperplasia caused by CYP17A1 gene mutations. The D487_F489 deletion in exon 8 and Y329fs in exon 6 are relatively frequent mutations of the CYP17A1 gene in China that completely abolish the enzyme activity of P450c17. However, little remains known about steroid biosynthetic functions in carriers with these mutations in a single allele of the CYP17A1 gene, who are assumed to have 50% P450c17 activity. We investigated adrenal steroidogenic function in genotype-proven heterozygotes carrying such mutations in the CYP17A1 gene in vivo. PATIENTS AND DESIGN: Eight patients and fourteen family members from five families with 17OHD were recruited. The mutations of the CYP17A1 gene in these individuals were screened by sequencing. The hormonal response to cosyntropin (ACTH) was evaluated in the 14 genotype-proven carriers and 45 age- and gender-matched normal controls. RESULTS: Fourteen carriers of the CYP17A1 mutation - seven with the D487_F489 deletion, six with Y329fs and one with H373L - were identified from the five families with 17OHD. Compared with normal controls, carriers showed lower basal and ACTH-stimulated cortisol levels but higher ACTH-stimulated corticosterone levels. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of the normal controls at the baseline and after cosyntropin stimulation. Similarly, the progesterone levels and the ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than those of the normal controls, both before and after ACTH stimulation. CONCLUSION: Genotype-proven carriers of the CYP17A1 mutation who lack apparent clinical symptoms exhibit decreased adrenal 17alpha-hydroxylase activity and altered adrenal gland reserve for steroid biosynthesis.


Assuntos
11-Hidroxicorticosteroides/sangue , Hiperplasia Suprarrenal Congênita/genética , Esteroide 17-alfa-Hidroxilase/genética , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Adulto , Estudos de Casos e Controles , Cosintropina , Análise Mutacional de DNA , Feminino , Genótipo , Hormônios , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto Jovem
13.
Planta Med ; 76(2): 128-32, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19653143

RESUMO

The ubiquitin-proteasome pathway has an important role in regulating apoptosis and the cell cycle. The function of proteasomes is mediated by three main catalytic activities: (1) chymotrypsin-like (CT-L), (2) trypsin-like (T-L), and (3) peptidylglutamyl peptide hydrolyzing (PGPH). Recently, proteasome inhibitors have been revealed to have an antitumor effect, and have been used to treat cancers such as multiple myeloma. Previous studies have reported that some flavonoids can inhibit proteasome activity in tumor cells. To further investigate the proteasome-inhibitory mechanism of flavonoids, we examined the effects of the plant flavonoids apigenin, chrysin, and luteolin on the three individual catalytic activities in various cancer cell lines. Using fluorogenic substrates specific for proteasome catalytic subunits, we demonstrated the subunit specificity of each flavonoid. Addition of apigenin, chrysin and luteolin inhibited CT-L and T-L catalytic activities in a dose-dependent manner, whereas their effect on PGPH catalytic activity was weak. Our study suggested that these flavonoids have a specific role in inhibition of CT-L and T-L proteasome catalytic activities.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Quimotripsina/metabolismo , Flavonoides/farmacologia , Neoplasias/metabolismo , Extratos Vegetais/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Tripsina/metabolismo , Antineoplásicos Fitogênicos/uso terapêutico , Apigenina/farmacologia , Apigenina/uso terapêutico , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Flavonoides/uso terapêutico , Humanos , Hidrólise , Luteolina/farmacologia , Luteolina/uso terapêutico , Neoplasias/tratamento farmacológico , Peptídeos/metabolismo , Extratos Vegetais/uso terapêutico , Ubiquitina
14.
Hum Mutat ; 30(9): E855-65, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19551906

RESUMO

Leydig cell hypoplasia (LCH) is a rare form of male pseudohermaphroditism caused by inactivating mutations in the luteinizing hormone receptor gene (LHCGR). The majority of LHCGR mutations are located in the coding sequence, resulting in impairment of either LH/CG binding or signal transduction. We report a Chinese family with two siblings (46, XY and 46, XX) carrying a missense mutation (c. 455 T>C, p. Ile152Thr) and a splice site mutation (c. 537-3 C>A). Computational analysis of the missense mutation in the three-dimensional structural model predicted it might influence the distribution of hydrogen bonds and intermolecular contacts between the hormone and receptor. Consistent with these findings, in vitro mutant analysis revealed a marked impairment of human chorionic gonadotropin binding and signal transduction. The splice-acceptor mutation (c. 537-3 C>A) resulted in abnormal splicing of LHCGR mRNA, skipping exon 7. This report expands the genotypic spectrum of LHCGR mutations, with relevant implications for the molecular analysis of this gene.


Assuntos
Transtornos do Desenvolvimento Sexual/genética , Mutação de Sentido Incorreto , Sítios de Splice de RNA/genética , Receptores do LH/genética , Povo Asiático , Sequência de Bases , Criança , Família , Feminino , Heterozigoto , Humanos , Modelos Moleculares , Conformação Proteica , RNA Mensageiro/metabolismo , Receptores do LH/metabolismo
15.
J Agric Food Chem ; 66(39): 10163-10168, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30200767

RESUMO

Bioassay-guided fractionation of the supernatant of the biocontrol strain Bacillus amyloliquefaciens W1 led to the isolation of eight acaricidal cyclodipeptides from the active fractions by column chromatography separation and HPLC purification. The chemical structures of these compounds were identified as cyclo-(Gly-l-Phe), 2, cyclo-(l-Phe- trans-4-OH-l-Pro), 3, cyclo-(Gly-l-Tyr), 4, cyclo-(l-Ala-l-Pro), 5, cyclo-(l-Pro- trans-4-OH-l-Pro), 6, cyclo-(Gly-l-Pro), 7, cyclo-(l-Pro-l-Pro), 8, and cyclo-(l-Tyr- trans-4-OH-l-Pro), 9. Those cyclodipeptides displayed significant acaricidal activities with LC50 values of 13.85-98.24 µM. Cyclo-(l-Tyr- trans-4-OH-l-Pro) (LC50 13.85 µM) was five times more effective than the positive control abamectin (LC50 72.06 µM). The results indicated that the hydroxyl group is an important component. This is the first report on the acaricidal capabilities of cyclodipeptides against Tetranychus urticae. The results revealed that the acaricidal activity of the biocontrol strain B. amyloliquefaciens W1 was dependent on its constituent cyclodipeptides, which have the potential to be safe and environmentally friendly acaricides.


Assuntos
Acaricidas/toxicidade , Bacillus amyloliquefaciens/química , Peptídeos Cíclicos/toxicidade , Tetranychidae/efeitos dos fármacos , Acaricidas/química , Acaricidas/metabolismo , Animais , Bacillus amyloliquefaciens/metabolismo , Dose Letal Mediana , Peptídeos Cíclicos/química , Peptídeos Cíclicos/metabolismo , Controle Biológico de Vetores , Tetranychidae/crescimento & desenvolvimento
17.
Ying Yong Sheng Tai Xue Bao ; 28(1): 142-150, 2017 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29749198

RESUMO

In the winter-wheat and summer-maize multiple cropping system in lime concretion black soil of Huanghuaihai Plain, the effects of three tilling methods (conventional tillage, rotary tillage, subsoiling tillage) in wheat season coupling with three nitrogen treatments (120 kg·hm-2, 225 kg·hm-2, 330 kg·hm-2) before maize sowing on the activities of microorganisms and enzymes re-lated nitrogen transformation, and inorganic nitrogen content in the rhizosphere soil during the main growth stages of maize, as well as the yield were investigated. The results showed that the rotary tillage had the highest ammonification intensity, and the more nitrogen was put in, the higher were the activities of microorganisms and enzymes related to soil nitrogen transformation. The activities of nitrification, denitrification and urease of subsoiling tillage was significantly higher than those of conventional and rotary tillage. Furthermore, in subsoiling tillage treatment, increasing nitrogen fertili-zer could promote soil nitrogen transformation while excessive nitrogen input inhibited soil nitrogen transformation, though the latter had higher yield and soil inorganic nitrogen content. The treatment of subsoiling tillage coupling with 225 kg·hm-2 nitrogen, was best for soil nitrogen transformation while the treatment of subsoiling tillage coupling with 330 kg·hm-2 nitrogen, had the highest corn yield.


Assuntos
Nitrogênio , Triticum , Zea mays , Agricultura , Solo
18.
Oncotarget ; 7(47): 77622-77634, 2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27769058

RESUMO

Bortezomib (BTZ), a proteasome inhibitor, is the first proteasome inhibitor to be used in clinical practice. Here we investigated the mechanisms underlying acquired bortezomib resistance in hepatocellular carcinoma (HCC) cells. Using stepwise selection, we established two acquired bortezomib-resistant HCC cell lines, a bortezomib-resistant HepG2 cell line (HepG2/BTZ) and bortezomib-resistant HuH7 cell line (HuH7/BTZ). The 50% inhibitory concentration values of HepG2/BTZ and HuH7/BTZ were respectively 15- and 39-fold higher than those of parental cell lines. Sequence analysis of the bortezomib-binding pocket in the ß5-subunit showed no mutation. However, bortezomib-resistant HCC cells had increased expression of ß1 and ß5 proteasome subunits. These alterations of proteasome expression were accompanied by a weak degree of proteasome inhibition in bortezomib-resistant cells than that in wild-type cells after bortezomib exposure. Furthermore, bortezomib-resistant HCC cells acquired resistance to apoptosis. Bortezomib up-regulated pro-apoptotic proteins of the Bcl-2 protein family, Bax and Noxa in wild-type HCC cells. However, in bortezomib-resistant HCC cells, resistance to apoptosis was accompanied by loss of the ability to stabilize and accumulate these proteins. Thus, increased expression and increased activity of proteasomes constitute an adaptive and auto regulatory feedback mechanism to allow cells to survive exposure bortezomib.


Assuntos
Bortezomib/farmacologia , Carcinoma Hepatocelular/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Complexo de Endopeptidases do Proteassoma/genética , Regulação para Cima
19.
Biomed Pharmacother ; 82: 399-405, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27470378

RESUMO

BACKGROUND: Imbalance in bone remodeling causes osteoporosis. PURPOSE: In the present study, we identified that protocatechuic acid inhibits osteoclast differentiation and induces apoptosis in RAW264.7 murine macrophage cells. METHODS: Tartrate-resistance acid phosphatase (TRAP) activity was used to determine osteoclast formation. Oxidative stress was analyzed through ROS, lipid peroxide and antioxidant enzyme activities. Osteoclast and inflammatory marker expressions were determined through western blot. Apoptosis induction was determined through membrane potential analysis, Cyt c release and caspase activation. RESULTS: Protocatechuic acid dose dependently reduced RANKL-induced tartrate-resistance acid phosphatase (TRAP) activity and multinucleated osteoclasts formation. Protocatechuic acid inhibited oxidative stress by reducing ROS and lipid peroxide levels with concomitant increase in antioxidant status. Osteoclast specific marker expression (MMP, c-Src, TRAP, TRAF-6, Cathepsin) and transcription factor AP-1 and NFATc1 expression were significantly down regulated by protocatechuic acid. Further, MAPK activation and inflammatory proteins such as NF-kB and COX-2 expressions were significantly down regulated by protocatechuic acid treatment. Further, protocatechuic acid enhanced Nrf-2 translocation into the nucleus. In mature osteoclasts, protocatechuic acid induced apoptosis by inducing mitochondrial membrane potential, cytochrome c release and caspase activation. INTERPRETATION: The present findings shows evidence that, protocatechuic acid prevents osteoclast differentiation through regulating oxidative stress, inflammation and inducing apoptosis in RAW264.7 murine macrophage cells.


Assuntos
Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Osteoclastos/citologia , Animais , Biomarcadores/metabolismo , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/farmacologia , Células RAW 264.7 , Fatores de Transcrição/metabolismo
20.
Zhongguo Gu Shang ; 29(11): 982-988, 2016 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-29292632

RESUMO

OBJECTIVE: To retrospectively study postoperative Garden III femoral neck fractures in the elderly so as to explore the different degree of displacement of Garden III femoral neck fracture, and discuss the basis and clinical significance of the subtype classification. METHODS: A total of 492 patients with complete clinical data out of the 1397 patients with femoral neck fractures treated by closed reduction and internal fixation with cannulated compression screws from September 2005 to September 2010 were included in the study. Each patient's frontal Garden Index was measured. On the basis of the frontal Garden Index, these cases were divided into three types:type A, which frontal Garden Index was more than or equal to 140°, included 53 males and 84 females with an average age of(65.3±7.2) years old ranging from 60 to 75 years old; type B, more than 120°and less than 140°, included 79 males and 172 females with an average age of (67.5±3.6) years old;and type C, less than or equal to 120°, included 38 males and 66 with an average age of(68.6±5.7) years old. Aspects were followed up including complications, consequences and hip joint function. The fracture healing and femoral head necrosis were compared among three types. RESULTS: Operative incision of 492 cases was primary healing, and no infection and other complications occurred. All patients were followed up from 2 to 10 years with an average of 6.3 years, the healing of femoral neck fracture occurred in 432 cases, and the total union rate was 87.8%. Femoral head necrosis occurred in 83 cases, and the total necrosis rate of femoral head was 16.9%. The nonunion rate of type A was 6.6%, type B was 13.5%, and type C was 16.3%, there were significant differences among three types(χ²2AB=4.377, P=0.036;χ²2AC=5.872, P=0.015;χ²2BC=0.469, PBC=0.494). The necrosis rate of femoral head of group A was 8.8%, group B was 16.7%, and group C was 27.9%, there were significant differences among three groups(χ²2AB=4.704, P=0.030;χ²2AC=15.317, P=0.000;χ²2BC=5.715, P=0.017). CONCLUSIONS: It is different for the degree of displacement of Garden III femoral neck fracture in the elderly. Based on frontal Garden Index to differentiate degree of fracture displacement, Garden III femoral neck fracture would be divided into A, B and C subtypes. The prognosis of Garden III femoral neck fracture in the elderly is negatively related to its degree of displacement, which has clinical significance to make treatment plan for Garden III femoral neck fracture in the elderly.


Assuntos
Fraturas do Colo Femoral/classificação , Fraturas do Colo Femoral/cirurgia , Idoso , Feminino , Fixação Interna de Fraturas , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
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