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1.
Food Funct ; 10(9): 5752-5758, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31453624

RESUMO

Phloretin, abundantly present in apples, pears and other fruits, has been found to have antioxidant, immunosuppressive and anti-inflammatory activities. It has been reported that oral administration of phloretin dose-dependently increased feed intake in mice, but the mechanism is unclear yet. The aim of this study was to investigate the effect of dietary phloretin supplementation on the feed intake in C57BL/6J mice and to identify its mechanism. Here, sixty C57BL/6J mice (28-day age) were randomly chosen for four dietary treatments and fed a basal diet or a basal diet supplemented with 0.1%, 0.2%, and 0.3% phloretin, respectively, in a 6-week trial. We showed that mice in the 0.1%, 0.2%, and 0.3% phloretin-supplemented groups had increased accumulative feed intake compared with the control group. Furthermore, dietary phloretin supplementation significantly increased the ghrelin mRNA level in the stomach and hypothalamus, and decreased the cholecystokinin (CCK) mRNA level in the duodenum in a dose-dependent manner. The mRNA levels of neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin and melanocortin receptors 4 (MC4R), and pro-opiomelanocortin (POMC) in the hypothalamus were altered in response to dietary phloretin supplementation. Moreover, we confirmed that dietary phloretin supplementation reduced the expressions of miR-488 and miR-103, two feed intake-related miRNAs. Our present study provides evidence that dietary phloretin supplementation could increase feed intake in mice, which might be attributed to the stimulation of the hypothalamic feeding center via ghrelin, miRNAs (miR-103 and miR-488) and feeding signal factor-related genes (NPY, AgRP, MC4R and POMC), and to the inhibition of CCK to increase gastric emptying.

2.
Biol Trace Elem Res ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432444

RESUMO

Dietary zinc status was recently approved to exert a powerful influence on liver health, and zinc deficiency results in hepatic injury caused by fat deposition, inflammation, and oxidant stress, but the effect of zinc on hepatic lipid metabolism and liver injury in meat duck has not been well defined. To determine the hepatoprotective effects of graded zinc glycine in meat ducks. A total of 384 1-day-old male meat ducks were subjected to 5 weeks feeding program with three experimental diets: (1) low-zinc diet, (2) adequate-zinc diet, and (3) high-zinc diet. Blood and liver samples were collected for biochemical analysis, gene expression analysis, and histopathological study. Diet with low zinc increased hepatic lipid content and triglyceride concentration. Meat ducks fed low-zinc diet exhibited considerably increased serum alanine aminotransferase (ALT) activity than birds fed other diets among all groups (P < 0.05). Low zinc administration also notably induced hepatocyte apoptosis and stimulated hepatic inflammatory gene expression. Adequate or high zinc supplementation increased hepatic zinc level, reduced hepatic lipid deposition and hepatosomatic indices through suppressing the expression of lipogenic genes including fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (P < 0.05), and upregulated the mRNA expression of both fatty acid secretion and ß-oxidation, including carnitine palmitoyltransferase 1a (Cpt1a), peroxisome proliferator-activated receptor (PPAR)α, and apolipoprotein B (ApoB) (P < 0.05). Dietary zinc addition also declined hepatic mRNA expression of interleukin (IL)-1ß and IL-6 (P < 0.05). Furthermore, diets with adequate or high zinc significantly decreased serum ALT activity and hepatocyte apoptosis. These data revealed that supplementing adequate- or high-zinc glycine efficiently protects liver injury by attenuating lipid deposition and hepatic inflammation.

3.
Toxins (Basel) ; 11(7)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261655

RESUMO

A novel naturally-occurring bradykinin-related peptide (BRP) with an N-terminal extension, named RVA-Thr6-Bradykinin (RVA-Thr6-BK), was here isolated and identified from the cutaneous secretion of Odorrana hejiangensis (O. hejiangensis). Thereafter, in order to evaluate the difference in myotropic actions, a leucine site-substitution variant from Amolops wuyiensis skin secretion, RVA-Leu1, Thr6-BK, was chemically synthesized. Myotropic studies indicated that single-site arginine (R) replacement by leucine (L) at position-4 from the N-terminus, altered the action of RVA-Thr6-BK from an agonist to an antagonist of BK actions on rat ileum smooth muscle. Additionally, both BK N-terminal extended derivatives (RVA-Thr6-BK and RVA-Leu1, Thr6-BK) exerted identical myotropic actions to BK, such as increasing the frequency of contraction, contracting and relaxing the rat uterus, bladder and artery preparations, respectively.

4.
Biomolecules ; 9(7)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261722

RESUMO

Protease inhibitors that were identified from amphibian skin secretions with low molecular weights and potent inhibitory activity were thought to be potential candidates for novel peptide drugs. Here, a novel peptide with trypsin inhibitory activity was found in the skin secretion of the Chinese bamboo leaf odorous frog, Odorrana versabilis. Based on the sequence alignments of sequencing results, the novel peptide (ALKYPFRCKAAFC) was named as Kunitzin-OV. The synthetic replicate of Kunitzin-OV was subjected to a series of functional assays, and it exhibited a trypsin inhibitory activity with a Ki value of 3.042 µM, whereas, when Lys-9 at P1 position was substituted by Phe, trypsin inhibitory activity was undetected and the chymotrypsin inhibitory activity was optimized with a Ki value of 2.874 µM. However, its protease-binding loop was catabolized by trypsin during the trypsin cleavage test. In conclusion, Kunizin-OV is a novel peptide with trypsin inhibitory activity as a member of kunitzins, which is a non-typical Kunitz-like trypsin inhibitor with a highly conserved reactive site (K-A) and quite a short sequence.

5.
Drug Alcohol Depend ; 202: 168-171, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352306

RESUMO

BACKGROUND: Cocaine is a commonly abused drug and there is no approved medication specifically to treat its addiction or overdose. Bacterial cocaine esterase (CocE)-derived RBP-8000 is currently under clinical development for cocaine overdose treatment. It is proven to be effective for human use to accelerate cocaine metabolism into physiologically inactive products. Besides cocaine, RBP-8000 may hydrolyze the neurotransmitter acetylcholine (ACh), however, no study has reported its cholinesterase activity. The present study aims to examine RBP-8000's cholinesterase activity and substrate selectivity to address the potential concern that this enzyme therapy might produce cholinergic side-effects. METHODS: Both computational modeling and experimental kinetic analysis were carried out to characterize the potential cholinesterase activity of RBP-8000. Substrates interacting with RBP-8000 were modeled for their enzyme-substrate binding complexes. In vitro enzymatic kinetic parameters were measured using Ellman's colorimetric assay and analyzed by Michaelis-Menten kinetics. RESULTS: It is the first demonstration that RBP-8000 catalyzes the hydrolysis of acetylthiocholine (ATC). However, its catalytic efficiency (kcat/KM) against ATC is 1000-fold and 5000-fold lower than it against cocaine at 25 °C and 37 °C, respectively, suggesting RBP-8000 has the desired substrate selectivity for cocaine over ACh. CONCLUSION: Given the fact that clinically relevant dose of RBP-8000 displays insignificant cholinesterase activity relative to endogenous cholinesterases in human, administration of RBP-8000 is unlikely to produce any significant cholinergic side-effects. This study provides supplemental evidences in support of further development of RBP-8000 towards a clinically used pharmacotherapy for cocaine overdose.

6.
J Anim Physiol Anim Nutr (Berl) ; 103(5): 1512-1520, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31268198

RESUMO

Apple polyphenols (APPs) are biologically active flavonoids that have antioxidant, anti-inflammatory, improving insulin sensitivity, hypocholesterolaemic effect and antiviral properties. This study was conducted to explore effects of dietary APPs supplementation on antioxidant activities and lipid metabolism in weaned piglets. Fifty-four weaned piglets (half male and female) were randomly divided into three groups with six replicates in each group and three piglets in each repetition. Piglets were fed control diet (basal diet) or a control diet supplemented with 400 mg/kg or 800 mg/kg APPs for 6 weeks. Blood and liver samples were collected to determine biochemical, antioxidant and lipid metabolism parameters. Here we showed that dietary APPs supplementation increased HDL-C and decreased T-CHO, TG and LDL-C concentrations. Dietary APPs supplementation increased antioxidative capacity in serum and CAT activity in liver, and significantly increased the mRNA expressions of CAT, GST and SOD1 in liver. ACC mRNA level and LPL activity were tended to decrease by APPs. HMG-CoAR, CTP7A1, CD36 and FATP1 mRNA levels were decreased by APPs, while LDL-R, PGC-1α, Sirt1 and CPT1b mRNA levels were increased by 400 mg/kg APPs. No alterations in growth performance were found in all treatments. This study firstly provided the evidence that dietary APPs supplementation could enhance systemic antioxidant capacity and improve lipid metabolism in weaned piglets. The mechanism by which APPs improve lipid metabolism might be through regulating hepatic cholesterol metabolism and increasing fatty acid oxidation, and decreasing fatty acid uptake and de novo synthesis.

7.
Acta Otolaryngol ; 139(10): 908-912, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31343387

RESUMO

Background: Neck lymph node status is the chief prognostic index in patients with head and neck squamous cell carcinoma (SCC), yet the management of a clinically negative neck in this setting is still controversial, especially in patients with laryngeal SCC (LSCC). Objectives: To evaluate the efficacy of selective neck dissection (SND) to control occult disease in patients with LSCC and clinically negative (cN0) necks. Materials and methods: Medical records of 1476 patients with cN0 LSCC were analyzed. In conjunction with primary treatment, 126 (8.5%) underwent at least unilateral elective neck dissection, whereas most 1350 (91.5%) followed a wait-and-see protocol. Prognostic significance was indicated by the Kaplan-Meier survival estimates. Results: The rate of occult neck disease was 15%. Five-year overall and disease-free survival rates were 74.4% and 66.7%, respectively. Prognosis was closely related to T stage, preoperative tracheotomy, and postoperative recurrence. There was no significant correlation with age, sex, or preoperative neck dissection; but in patients with supraglottic LSCC, the relation between prognosis and preoperative neck dissection was significant, with fewer neck and local recurrences than the wait-and-see group (p < .05). Conclusions and significance: Selective neck dissection is serving as an accurate prognostic tool in patients with supraglottic laryngeal cancers.

8.
Int J Biochem Cell Biol ; 114: 105573, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325628

RESUMO

It has been clinically documented that maduramicin (Mad), a polyether ionophore antibiotic widely used in the control of coccidiosis in poultry worldwide, can elicit skeletal muscle degeneration, heart failure, and even death in animals and humans, if improperly used. Here, we show that Mad induced apoptosis dose-dependently, which was associated with impaired autophagic flux in skeletal myoblast (C2C12 and L6) cells. This is supported by the findings that Mad treatment resulted in increase of autophagosomes with a concomitant elevation of LC3-II and p62 in the cells. Also, Mad increased co-localization of mCherry and GFP tandem-tagged LC3 puncta in the cells, suggesting a blockage of autophagic flux. Furthermore, addition of chloroquine (CQ) strengthened the basic and Mad-enhanced LC3-II and p62 levels, autophagosome formation and cell apoptosis, whereas pretreatment with rapamycin alleviated the effects in the cells exposed to Mad. Moreover, we noticed that Mad treatment inactivated Akt dose-dependently. Inhibition of Akt with inhibitor X potentiated Mad-induced decrease in phosphorylated Akt, and increases in LC3-II and p62 levels, autophagosome formation and cell apoptosis, whereas ectopic expression of constitutively active Akt rendered resistance to these events. Collectively, these results indicate that Mad inactivation of Akt impairs autophagic flux leading to accumulated autophagosomes-dependent apoptosis in skeletal myoblast cells. Our findings suggest that manipulation of Akt activity to improve autophagic flux is a promising strategy against Mad-induced myotoxicity.

9.
Acta Otolaryngol ; 139(9): 803-809, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31240973

RESUMO

Background: Laryngeal carcinoma should be treated with the intent of organ-sparing, and supracricoid partial laryngectomy with cricohyoidoepiglottopexy (CHEP) might be an important option. Aims/objectives: The purpose of this study was to evaluate the clinical outcomes of glottic carcinoma patients treated with CHEP. Materials and methods: A series of 164 cases with glottic carcinoma undergoing CHEP from 2006 to 2010 was retrospectively analyzed. Results: The 10-year overall survival (OS) rate, disease-specific survival (DSS) rate, and disease-free survival (DFS) rate were 77.6%, 78.8%, 74.1%, respectively. The OS, DSS, and DFS of patients with stage T1 were higher than patients with stages T2 and T3. Patients with locoregional recurrence and distant metastases had lower OS and DFS than patients with neither recurrence nor metastasis. The DFS of patients with advanced laryngeal carcinoma was worse than that of patients with early-stage carcinoma. T2 and T3 stages, locoregional recurrence, and distant metastases had predictive value regarding patient survival. Additionally, the decannulation rate of postoperative patients was 95.1%, and the nasogastric feeding tube removal rate was 100%. Conclusions and Significance: CHEP provided reliable oncologic and functional outcomes, and it should be considered as a standard function-sparing option for glottic T1b, T2, and selected T3 carcinoma patients.

10.
J Cell Physiol ; 2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31230374

RESUMO

Skeletal muscle development is a highly organized process controlled by evolutionarily conserved networks of transcription factors, transferrable signaling molecules, and noncoding RNAs that coordinate the expression of large numbers of genes. MicroRNAs (miRNAs) have emerged as prominent players of multiple biological processes by silence of specific mRNAs or by suppression of protein translation. It has become to be clear cumulatively that miRNAs control of expression of gene targets are particularly important during skeletal myogenesis. Signaling pathways, especially IGF/AKT/mTOR pathway and TGF-ß signaling, have also determined to act as critical regulators in the regulation of myogenic program. In the last decades, growing evidence has seen a rapid expansion of our knowledge of miRNA-mediated control of expression of target genes and signaling pathways, in which miRNAs coordinately regulate myogenic process through their targets or through signaling pathways. Here, we summarize the current findings of miRNAs and signaling pathways in the regulation of skeletal myogenesis, focusing on miRNAs' target genes and IGF/AKT/mTOR pathway and TGF-ß signaling.

11.
Anim Sci J ; 90(8): 990-998, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31251457

RESUMO

The study was conducted to investigate the effects of dietary leucine on antioxidant activity and expression of antioxidant- and mitochondrial-related genes in longissimus dorsi muscle and liver of piglets. Three diets were formulated with different levels of supplemented leucine (0%, 0.25%, 0.5%). Results showed that supplementation of 0.25% leucine significantly increased antisuperoxide anion (ASA) and antihydroxyl radical (AHR) levels and activities of total superoxide dismutade (T-SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and total antioxidant capacity (T-AOC) in serum, longissimus dorsi muscle and liver of piglets as compared with the control group. The SOD2, catalase (CAT), GPx, GST, glutathione reductase (GR), and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels in longissimus dorsi muscle and liver were significantly increased by 0.25% leucine supplementation. However, the malondialdehyde (MDA) content and the mRNA level of Kelch-like ECH-associated protein 1 (Keap1) exhibited an opposite tendency. Additionally, supplementation of 0.25% leucine significantly increased the mRNA levels of mitochondrial-related genes in longissimus dorsi muscle and liver of piglets. Results suggested that supplementation of 0.25% leucine improved antioxidant activity and mitochondrial biogenesis and function of piglets, which was related to the increase in antioxidant enzymes activities and upregulation of expression of antioxidant- and mitochondrial-related genes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31180828

RESUMO

OBJECTIVE: Direct interaction between the brain and muscle is significant for investigating the oscillation mechanisms in the motor control system. To our knowledge, the partial directed coherence (PDC) method is sufficient to reflect the direct interaction among multivariate time series in the frequency domain, but fails to eliminate the spectral overlap among frequency bands. Therefore, we expanded the PDC method and constructed a novel method, named variational-mode-decomposition-based PDC (VMDPDC), to describe the direct interaction on specific frequency bands. To verify this, we made a comparison with the Granger causality (GC), PDC and FIR-based PDC (FIRPDC) methods in two numerical models (bivariate coupling model and multivariate coupling model). After that, we applied this method to analyze the functional corticomuscular coupling (FCMC) during steady-state grip task. Simulation results showed that, compared with the GC, PDC and FIRPDC methods, the VMDPDC method could accurately detect the direct interaction on specific frequency bands. The results on experimental data showed that the direct interaction in FCMC mainly focused on the alpha (8-15 Hz), beta (15-35 Hz) and gamma (35-60 Hz) bands. Further analysis demonstrated that the coupling strength in descending direction was significantly higher than that in the opposite direction. Both simulation and experimental results indicated that the proposed method could effectively describe the direct interaction on specific frequency bands. This study also provides a theoretical foundation for further exploration on the mechanism of the motor control.

13.
Thorac Cancer ; 10(7): 1590-1596, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31183998

RESUMO

BACKGROUND: This real-world study assessed the efficacy and toxicity of anlotinib as salvage treatment in Chinese patients with advanced non-small cell lung cancer (NSCLC). METHODS: The medical records of 81 patients with advanced NSCLC who had failed at least two lines of chemotherapy were retrospectively collected. All patients were administered anlotinib treatment until disease progression or intolerance as a result of adverse events. Survival curves were created using the Kaplan-Meier method. The log-rank test was used for univariate analysis of progression-free survival (PFS) between groups. Cox regression was used to estimate the statistically significant factors based on univariate analysis. RESULTS: The median PFS was five months (95% confidence interval [CI] 3.5-6.5). The objective response rate (ORR) was 7% and the disease control rate (DCR) was 84%. The following subgroups of patients had longer PFS (P < 0.05): squamous cell carcinoma, no brain or liver metastases, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and no previous VEGF-tyrosine kinase inhibitor treatment. The results of Cox regression indicated that an ECOG PS of 0-1 (hazard ratio 0.152, 95% CI 0.057-0.403; P = 0.00) and patients without brain metastases (hazard ratio 0.421, 95% CI 0.195-0.911; P = 0.028) had longer PFS following anlotinib treatment. CONCLUSION: Anlotinib, which is well tolerated, plays a significant role in the salvage treatment of advanced NSCLC. Patients with advanced NSCLC with an ECOG PS of 0-1 and no brain metastases achieved longer PFS following anlotinib salvage treatment.

14.
Food Funct ; 10(7): 4134-4142, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31241125

RESUMO

This study aimed to investigate the effect of putrescine on the immune function and intestinal bacteria of weaning piglets. Twenty-four male castrated weaning piglets on their 21st day were randomly assigned into four groups: control (basal diet) and treatment groups given basal diets supplemented with 0.05%, 0.1%, and 0.15% putrescine for 11 days. Results were as follows: (1) Dietary putrescine increased the villus height, width, height/crypt depth and surface area, and decreased the diarrhea index (P < 0.05). (2) Dietary putrescine increased the lysozyme and acid phosphatase activities and the amount of immunoglobulin M, antibacterial peptides, and transforming growth factor ß1, but decreased the mRNA levels of tumor necrosis factor α, interleukin-6, interleukin-8 and inducible nitric oxide synthase (P < 0.05). (3) Dietary putrescine increased the mRNA expression of the mammalian target of rapamycin, signal transducer and activator of transcription, and Janus kinase 2 but decreased the mRNA expression of nuclear factor-kappa B P65 (P < 0.05). (4) Dietary putrescine increased the population of total bacteria, Lactobacillus, and Bifidobacterium and decreased that of Escherichia coli in the colon and cecum (P < 0.05). (5) Finally, dietary putrescine increased the concentrations of butyrate and total volatile fatty acids in the colon and those of acetate, propionate, and total volatile fatty acids in the cecum (P < 0.05). Overall, putrescine can enhance intestinal development, improve immune functions, and regulate the population of intestinal bacteria in weaning piglets.

16.
Phys Chem Chem Phys ; 21(17): 8940-8944, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30985852

RESUMO

Two-dimensional binary hydrogen-bonded organic frameworks constructed from 1,3,5-benzenetricarboxylic acid (TMA) and 4,4'-biphenyldicarboxylic acid (BDA) on highly oriented pyrolytic graphite (HOPG) were investigated by scanning tunneling microscopy (STM) in heptanoic acid and octanoic acid solvents. High-resolution STM observations demonstrated that various assemblies of hydrogen-bonded networks are strongly dependent on the nature of the solvent. Well-ordered porous rectangular flowerlike networks were revealed at the heptanoic acid/HOPG interface, whereas two different coexisting densely packed guest-host BDA/TMA structures were observed at the octanoic acid/HOPG interface. It is suggested that the stabilization of the binary networks is possibly associated with the solvent chain length, and longer-chain solvents favored the formation of porous polymorphic networks.

17.
IEEE Trans Neural Syst Rehabil Eng ; 27(5): 1092-1102, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30908233

RESUMO

Functional corticomuscular coupling (FCMC) with different rhythmic oscillations plays different roles in neural communication and interaction between the central nervous system and the peripheral system. Larger methods, such as coherence and Granger causality (GC), have been used to describe the frequency band characteristics in the frequency domain, but they fail to account for the inherent complexity. Considering that the transfer entropy (TE) method as an information theory has advantages in complexity and direction, we extended it and proposed a novel method named transfer spectral entropy (TSE) to explore the local frequency band characteristics between two coupling signals. To verify this, we introduced a Henon model and a neural mass model to generate the simulation signals. We then applied the proposed method to explore the FCMC by analyzing the correlation between the EEG and EMG signals during steady-state force output. Simulation results showed that the TSE method, compared with the GC method, not only described the information interaction in the local frequency band but also restrained the "false coupling." In addition, the results also revealed that the TSE method was sensitive to coupling strength but not to the data length. Further analysis of the experimental data showed that beta1 (15-25 Hz) and beta2 (25-35 Hz) bands were prominent in the FCMC for both EEG-to-EMG and EMG-to-EEG directions. In addition, the statistical analysis of the significant area indicated that the coupling in the EEG-to-EMG direction was higher at the beta1 and beta2 bands than that in the EMG-to-EEG direction, and the coupling in the EMG-to-EEG direction was higher at the gamma1 band (35-45 Hz) than that in the opposition. The FCMC results complementarily refined the previous studies that mainly focused on the beta band (15-35 Hz). The simulation and experimental data expound the effectiveness of the TSE model to describe the information interaction in the local frequency band between two time series, and this study extends the relative studies on FCMC.

18.
Acta Otolaryngol ; 139(5): 432-438, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30848984

RESUMO

Primary subglottic carcinoma is rare and surgery is the most common therapeutic strategy for Chinese patients with this disease. To retrospectively evaluate surgically treated primary subglottic carcinoma treated with surgery. Patients with primary subglottic carcinoma who initially underwent surgery from 2005-2010 were grouped by surgical procedures with or without laryngeal function preservation and reviewed. Of 1815 patients with laryngeal cancer, 23 had a subglottic origin. Of these, 21 initially underwent surgery; 12 had 'early' (stage I/II) disease, and nine had 'advanced' (stage III/IV) disease. The actuarial 5-year OS was 73.9% [95% confidence interval (54.1% ∼ 93.7%)] for patients with squamous cell carcinoma. Among patients with early disease, the 5-year OS and DFS were 80% for partial laryngectomy and 71.4% for total laryngectomy. Patients with advanced disease underwent total laryngectomy, and the 5-year OS and DFS were 62.5%. Satisfactory oncologic outcomes can be achieved with initial surgery. Patients with early disease who underwent partial laryngectomy had a comparable prognosis to those who underwent total laryngectomy; deglutition and speech function were maintained.

19.
Mol Med Rep ; 19(5): 3441-3448, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30816533

RESUMO

Ataxia­telangiectasia (A­T) is an autosomal recessive chromosome breakage disorder caused by mutations in the ATM serine/threonine kinase (ATM) gene. Typically, it presents in early childhood with progressive cerebellar dysfunction, accompanied by immunodeficiency and oculocutaneous telangiectasia. In the present study, the clinical and genetic findings of a Chinese family affected with A­T in two live siblings, the proband (II­2) and his elder brother (II­1), as well as a fetus (II­3) were reported. General health, clinical neurological, electrophysiological (motor and sensory nerve conduction) and magnetic resonance imaging evaluations revealed that patients II­1 and II­2 had similar symptoms of ataxia, dysarthria, conjunctival hyperemia and elevated serum α­fetoprotein, whereas patient II­1 had earlier A­T onset at 2 years old and more serious problems with movement and intelligence. Targeted sequencing followed by Sanger sequencing revealed that these two patients carried the compound heterozygotes of a novel nonsense mutation c.5170G>T (p.Glu1724Ter) and a known nonsense mutation c.748C>T (p.Arg250Ter) in the ATM gene. Each mutation was inherited from an asymptomatic parent, which therefore confirmed the diagnosis of A­T. Given this, proband's mother performed prenatal diagnosis in her third pregnancy. Unfortunately, the fetus had the same causal mutations as its siblings and the pregnancy was terminated. The findings of the present study expanded the mutation spectrum of the ATM gene and may help in understanding the genetic basis of A­T, in order to guide genetic counseling and prenatal diagnosis.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Estudos de Associação Genética , Aconselhamento Genético , Mutação , Fenótipo , Alelos , Grupo com Ancestrais do Continente Asiático , Ataxia Telangiectasia/fisiopatologia , Biomarcadores , Cerebelo/patologia , Biologia Computacional , Análise Mutacional de DNA , Eletromiografia , Feminino , Genótipo , Humanos , Imagem por Ressonância Magnética , Masculino , Linhagem , Avaliação de Sintomas
20.
J Plant Physiol ; 236: 7-14, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30840921

RESUMO

Previous studies have documented mitochondrial dysfunction during the critical node (CN) of rice (Oryza sativa) seed aging, including a decrease in the capacity of NADH dependent O2 consumption. This raises the hypothesis that changes in the activity of NADH:ubiquinone oxidoreductase (complex I) may play a role in seed aging. The composition and activity of complex I was investigated at the CN of aged rice seeds. Using BN-PAGE and SWATH-MS 52 complex I subunits were identified, nineteen for the first time to be experimentally detected in rice. The subunits of the matrix arm (N and Q modules) were reduced in abundance at the CN, in accordance with a reduction in the capacity to oxidise NADH, reducing substrate oxidation and increase ROS accumulation. In contrast, subunits in the P module increased in abundance that contains many mitochondrial encoded subunits. It is proposed that the changes in complex I abundance subunits may indicate a premature re-activation of mitochondrial biogenesis, as evidenced by the increase in mitochondrial encoded subunits. This premature activation of mitochondrial biogenesis may under-pin the decreased viability of aged seeds, as mitochondrial biogenesis is a crucial event in germination to drive growth before autotrophic growth of the seedling is established.


Assuntos
Complexo I de Transporte de Elétrons/metabolismo , Mitocôndrias/metabolismo , Oryza/metabolismo , Sementes/metabolismo , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Complexo I de Transporte de Elétrons/fisiologia , Eletroforese em Gel de Poliacrilamida , Cromatografia Gasosa-Espectrometria de Massas , Immunoblotting , Mitocôndrias/fisiologia , Oryza/fisiologia , Sementes/fisiologia
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