RESUMO
Objective: To investigate the efficacy of mitomycin C (MMC) 0.02% for prevention of haze after transepithelial photorefractive keratectomy (Trans-PRK) for mild and moderate myopia. Methods: Retrospective cohort study. We reviewed medical records of 295 patients (588 eyes) who underwent Trans-PRK with or without use of MMC. There were 45 patients (90 eyes) in the mild myopia group (aged between 18 and 41 years; 37 males and 8 females; myopia diopter <3.00 D) and 250 patients (498 eyes) in the moderate myopia group (aged between 18 and 46 years; 168 males and 82 females; myopia diopter: 3.00 to 6.00 D). The two groups were divided into subgroups with MMC 0.02% and without MMC, respectively. The time of intraoperative application of MMC, if there was, was 15 s and 30 s in the mild myopia group and the moderate myopia group, respectively. The mean follow-up time was 6 months. Postoperative best corrected visual acuity (BCVA), spherical equivalent (SE) and haze were analyzed and compared using an independent Student t-test or Mann-Whitney U test between subgroups. Haze variables were compared using chi-square statistics. Results: Haze was quantified with Fantes from grade 0.5 to 4. In the mild myopia group, all haze grades were 0.5 within 3 months. The incidence of haze was 6.25% (2/32) in eyes treated with MMC and 8.62% (5/58) in eyes treated without MMC; there was no statistical significance (χ²=0.00, P>0.999). In the moderate myopia group, the incidence of haze was 9.19% (24/261) in eyes treated with MMC within 3 months; the grade was 0.5 in 91.67% (22/24) of eyes with haze and 1 in 8.33% (2/24). The incidence of haze was 29.53% (70/237) in eyes treated without MMC; the grade was 0.5 in 60.00% (42/70) of eyes with haze, 1 in 18.57% (13/70), and 2 in 5.71% (4/70) within 3 months, and 0.5 in 15.71% (11/70) after 3 months (χ²=12.36, P=0.002). In the mild myopia group, BCVA was 5.0(5.0, 5.1) versus 5.0(5.0, 5.1) in the subgroups with MMC and without MMC (Z=-0.34, P=0.733). In the moderate myopia group, BCVA was 5.0(5.0, 5.1) versus 5.0(5.0, 5.1) in the subgroups with and without MMC (Z=-2.05, P=0.040). In the mild myopia group, SE was (0.33±1.07) D versus (0.32±0.57) D in the subgroups with and without MMC (t=0.25, P=0.805). In the moderate myopia group, SE was (0.66±0.85) D versus (0.53±0.67) D in the subgroups with and without MMC (t=2.97, P=0.003). Conclusions: MMC 0.02% was effective in preventing haze after Trans-PRK in the treatment of moderate myopia. However, it was not effective in mild myopia.
Assuntos
Miopia , Ceratectomia Fotorrefrativa , Adolescente , Adulto , Alquilantes , Feminino , Humanos , Lasers de Excimer , Masculino , Mitomicina/uso terapêutico , Miopia/cirurgia , Refração Ocular , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual , Adulto JovemRESUMO
Objective: To clarify the clinical efficacy of Yiqi Huoxue recipe in the treatment of liver fibrosis of chronic viral hepatitis. Methods: An open, positive-drug, parallel-controlled study method was applied. A total of 207 cases of liver fibrosis with chronic hepatitis B and C diagnosed with liver biopsy and transient elastography were selected. According to the principle of syndrome differentiation in traditional Chinese medicine, self-made Yiqi Huoxue recipe (n = 127) and Fuzheng Huayu capsule (n = 80) were used for the treatment course of 24-48 weeks. Change score of TCM symptom, liver biochemistry, liver stiffness measurement (LSM), and noninvasive liver fibrosis index [aspartate transaminase to platelet ratio index (APRI), and fibrosis-4 score (FIB-4)] were compared between the two groups to evaluate the therapeutic effect of Yiqi Huoxue recipe on liver fibrosis. Results: Yiqi Huoxue recipe group and Fuzheng Huayu capsule group baseline LSM, APRI and FIB-4 was compared, and there was no statistically significant difference between them (P > 0.05). Yiqi Huoxue recipe and Fuzheng Huayu capsule received patients had improved symptom scores to a certain extent. Hepatic facies, discomfort over liver area, and soreness and weakness of waist and knees (P < 0.05) was significantly improved in Yiqi Huoxue recipe than Fuzheng Huayu capsule. Liver biochemical indicators (ALT, AST, GGT, ALP) had gradually relapsed with the extension of treatment duration and the normalization rate between the two groups after 24 to 48 weeks had reached 100% vs. 100%, 100% vs. 93.8%, 96.8% vs. 92.3% and 87.5% vs. 81.8%. After 12 weeks of treatment, APRI values ââof both groups had significantly reduced, and after 48 weeks of treatment, LSM values of both groups had significantly improved. Moreover, Yiqi Huoxue recipe FIB-4 score was significantly improved after 48 weeks of treatment, and the difference was statistically significant compared to Fuzheng Huayu capsule group (P < 0.05). After treatment, LSM, APRI, and FIB-4 total effectiveness in the two groups were 80.0% vs. 63.6%, P = 0.046; 68.4% vs. 52.0%, P = 0.052; 68.4% vs. 62.0%, P = 0.437, respectively. LSM total effectiveness was significantly higher in Yiqi Huoxue recipe treated group than Fuzheng Huayu capsule group. Conclusion: Traditional Chinese medicine Yiqi Huoxue decoction can be used as an optimal treatment for liver fibrosis of chronic viral hepatitis.
Assuntos
Medicamentos de Ervas Chinesas , Hepatite B Crônica , Cirrose Hepática , Aspartato Aminotransferases , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Humanos , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Medicina Tradicional ChinesaRESUMO
Objective: To compare the clinical outcomes between laser epithelial keratomileusis (LASEK) and transepithelial photorefractive keratectomy (TPRK) for treatment of myopia. Methods: Case-control study. We reviewed a total of 90 right eyes that underwent either LASEK or TPRK, with 45 eyes in each group (aged between 18 and 40 years; 9 males and 16 females in the LASEK group, and 30 males and 15 females in the TPRK group) from 2015 to 2016 in Peking Union Medical College Hospital and Tangshan Eye Hospital. All the patients were followed up for 6 months postoperatively. Pain, uncorrected visual acuity (UCVA), and haze were measured at postoperative 3 days, 7 days, 1 month, 3 months and 6 months, and compared using an independent Student t-test between the two groups. Degree of haze, eye pain score, and visual acuity were compared by the Mann-Whitney U test. Results: At 3 days, the pain score was 1 (0,3) in the LASEK group versus 0 (0,1) in the TPRK group (Z=5.643, P=0.001). The UCVA was 4.80±0.10 in the LASEK group versus 4.97±0.07 in the TPRK group (Z=6.930, P=0.000) at 3 days, 4.98±0.08 in the LASEK group versus 5.05±0.06 in the TPRK group (Z=8.147, P=0.000) at 7 days, and 5.02±0.05 in the LASEK group versus 5.06±0.06 in the TPRK group (Z=2.381, P=0.017) at 1 month. The UCVA was also measured at 3 months, 5.07±0.07 versus 5.10±0.07 (Z=1.632, P=0.103), and at 6 months, 5.10±0.07 versus 5.11±0.07 (Z=0.798, P=0.425), respectively, with no statistical significance. The residual diopter was (0.17±0.19) D in the LASEK group versus (0.17±0.20) D in the TPRK group (Z=0.097, P=0.923) at 1 month, (0.03±0.11) D versus (0.07±0.14) D (Z=0.166, P=0.096) at 3 months, (0.07±0.13) D versus (0.07±0.14) D (Z=0.002, P=0.978) at 6 months, respectively. The surface regularity index (SRI) was 0.48±0.09 in the LASEK group and 0.46±0.06 in the TPRK group (t=0.88, P=0.37) at 1 month, and 0.49±0.07 in the LASEK group versus 0.47±0.06 in the TPRK group (t=1.53, P=0.132) at 3 months. Transient haze was documented in 1 eye in each group at 1 month (4.4%), with a maximum index of 0.5. No haze was observed in either group at 6 months. Conclusion: TPRK has the advantages of faster early vision recovery and significantly less pain over LASEK. (Chin J Ophthalmol, 2019, 55: 122-126).
Assuntos
Ceratectomia Subepitelial Assistida por Laser , Ceratomileuse Assistida por Excimer Laser In Situ , Miopia , Ceratectomia Fotorrefrativa , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Lasers de Excimer , Masculino , Miopia/cirurgia , Estudos Prospectivos , Refração Ocular , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the clinicopathological features of different stages of primary biliary cirrhosis (PBC), and to provide a basis of evidence-based medicine for early identification and effective treatment of this disease. METHODS: A total of 130 patients with pathologically confirmed PBC and complete clinical data were enrolled and divided into early-stage group and late-stage group based on pathological results. A retrospective analysis was performed for patients' general information, clinical manifestations, laboratory examinations, and pathological changes. RESULTS: The PBC patients had a mean age of 43.5±7.1 years, with middle-aged female patients accounting for 89%. The most common symptom was fatigue, followed by jaundice, pruritus, and abdominal distension in the late stage. Of all patients, 11.5% were complicated by autoimmune disease. The level of aminotransferases tended to decrease with the progression of PBC and showed no significant differences between the two groups (P > 0.05). Most patients showed an increase in serum bilirubin, mainly direct bilirubin; serum total bilirubin and direct bilirubin tended to increase with disease progression and showed significant differences between the two groups (P < 0.01). The patients showed increases in the serum levels of alkaline phosphatase (ALP) andγ-glutamyl transpeptidase (GGT), but with the disease progression, the serum level of ALP increased and that of GGT decreased; the serum levels of ALP and GGT showed no significant differences between the early- and late-stage groups (P > 0.05). The positive rate of antimitochondrial antibody was 85%. The histopathological changes of PBC included severe lesions in the portal area and surrounding areas and slight lobular lesions. In the early stage, there were injuries of the interlobar bile ducts, proliferation of small bile ducts, aggregation and invasion of mononuclear cells in surrounding tissues, and the formation of lymphoid follicle-like structure; in the late stage, there were fibrotic expansion of the portal area, formation of fibrous septa and pseudolobuli, and even liver cirrhosis. CONCLUSION: PBC is commonly seen in middle-aged women and has an insidious onset. Early- and late-stage PBC have their own clinicopathological features. As for patients with no characteristic changes in serological test, liver biopsy should be performed to give a confirmed diagnosis and avoid missed diagnosis and misdiagnosis.
Assuntos
Cirrose Hepática Biliar/diagnóstico , Adulto , Fosfatase Alcalina/sangue , Ductos Biliares/patologia , Bilirrubina/sangue , Progressão da Doença , Fadiga/complicações , Feminino , Humanos , Icterícia/complicações , Cirrose Hepática Biliar/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Prurido/complicações , Estudos Retrospectivos , gama-Glutamiltransferase/sangueRESUMO
UNLABELLED: In this study, we found out a previously undefined function of icariin which restored the dynamic balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head (ONFH) via ABCB1-promoter demethylation. These findings provided important information regarding potential implication of icariin targeting epigenetic changes for the treatment of steroid -associated ONFH. INTRODUCTION: Here, we investigated whether icariin can also exert a beneficial role in the reactivation of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter demethylation. METHODS: Bone marrow was collected from the proximal femur in patients with steroid-associated ONFH (n = 20) and patients with new femoral neck fractures (n = 22), and then MSCs were isolated. We investigated cell viability, intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1 and oxidative stress-related genes, methylation extent at CpG islands of ABCB1 promoter, and osteogenic and adipogenic differentiation ability of MSCs from the femoral neck fractures group and from the steroid-associated ONFH group treated with or without icariin. RESULTS: We observed that MSCs from the steroid-associated ONFH group showed reduced proliferation ability, elevated ROS level, depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp activity, transcription level of ABCB1, and oxidative stress-related genes as well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid-associated ONFH group. Treatment with icariin obviously induced de novo P-gp expression, decreased oxidative stress, and promoted osteogenesis. CONCLUSION: Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH.
Assuntos
Metilação de DNA/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Flavonoides/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adipogenia/efeitos dos fármacos , Adulto , Idoso , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/farmacologia , Epigênese Genética/efeitos dos fármacos , Feminino , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/patologia , Glucocorticoides/efeitos adversos , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Osteogênese/efeitos dos fármacos , Regiões Promotoras Genéticas , Espécies Reativas de Oxigênio/metabolismoRESUMO
Klinefelter syndrome (KS) is the most common genetic cause of male infertility. Widespread development in assisted reproductive technology has provided non-mosaic KS patients with the opportunity of having biological children. Testosterone replacement therapy and micro-dissection testicular sperm extraction are effective sperm retrieval techniques for KS patients. Despite the success of sperm retrieval and intracytoplasmic sperm injection (ICSI), some areas of early aggressive hormonal spermatogenesis and appropriate management of KS remain controversial. Androgenotherapy, a common treatment for KS, carries a risk of decreasing focal spermatogenesis by lowering the gonadotropin content. Inadequately treated hypogonadism increases psychosocial morbidity in KS patients. Preventive care must be provided from the time of diagnosis, preferentially through a multidisciplinary approach. This indicates the need for improved genetic counseling of KS patients. The aim of this study was to report the prevalence of non-mosaic KS in a Chinese infertile male population. The rate of early diagnosis was lower in KS patients; most of these were diagnosed after rising concerns of reproductive capacity. The mean age of patients with sperm or germ cells was significantly lower, while the semen volume of these patients was significantly higher. However, the semen volume was negatively correlated with the age and ratio of luteinizing hormone/testosterone content in KS patients. Therefore, genetic counseling of KS patients should focus on early diagnosis and timely treatment, in addition to improving the quality of life of all KS patients. The use of testosterone replacement therapy and/ or micro-dissection testicular sperm extraction should be preferentially considered for fertility preservation.
Assuntos
Aconselhamento Genético/métodos , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/terapia , Adulto , China , Terapia de Reposição Hormonal , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/terapia , Cariótipo , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/fisiopatologia , Hormônio Luteinizante/sangue , Masculino , Qualidade de Vida , Técnicas de Reprodução Assistida , Recuperação Espermática , Espermatogênese/genética , Testosterona/administração & dosagem , Testosterona/sangueRESUMO
Chromosomal abnormality is the most common genetic cause of male infertility, particularly in cases of azoospermia, oligozoospermia, and recurrent spontaneous abortion. Chromosomal rearrangement may interrupt an important gene or exert position effects. The functionality of genes at specific breakpoints, perhaps with a specific role in spermatogenesis, may be altered by such rearrangements. Structural chromosome abnormalities are furthermore known to increase the risk of pregnancy loss. In this study, we aimed to assess chromosomal defects in infertile men from Jilin Province, China, by genetic screening and to evaluate the relationship between structural chromosome abnormalities and male infertility. The prevalence of chromosomal abnormalities among the study participants (receiving genetic counseling in Jilin Province, China) was 10.55%. The most common chromosome abnormality was Klinefelter syndrome, and the study findings suggested that azoospermia and oligospermia may result from structural chromosomal abnormalities. Chromosome 1 was shown to be most commonly involved in male infertility and balanced chromosomal translocation was identified as one of the causes of recurrent spontaneous abortion. Chromosomes 4, 7, and 10 were the most commonly involved chromosomes in male partners of women experiencing repeated abortion.
Assuntos
Aberrações Cromossômicas , Testes Genéticos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Adolescente , Adulto , Azoospermia/diagnóstico , Azoospermia/epidemiologia , Azoospermia/genética , China/epidemiologia , Aconselhamento Genético , Testes Genéticos/métodos , Humanos , Infertilidade Masculina/epidemiologia , Cariótipo , Cariotipagem , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Oligospermia/diagnóstico , Oligospermia/epidemiologia , Oligospermia/genética , Análise do Sêmen , Adulto JovemRESUMO
Objective: To investigate the effect of endoscopic thyroidectomy and open thyroidectomy on parathyroid function in patients with thyroid cancer. Methods: The clinical data of 73 patients with thyroid cancer who met the inclusion criteria in Zhengzhou Central Hospital Affiliated to Zhengzhou University from July 2018 to September 2019 were retrospectively analyzed, including 17 males and 56 females, aged 19-55 years. The patients underwent routine thyroidectomy (group A, n=31), oral endoscopic thyroidectomy by vestibular approach (group B, n=19) or transthoracic thyroidectomy (group C, n=23), and all patients received central neck dissection. The levels of parathyroid hormone (PTH) and serum calcium after operation were compared among three groups. SPSS 21.0 software and GraphPad Prism v6.01 were used for statistical analysis. Results: After operation, the mean levels of PTH and serum calcium in three groups were significantly decreased (all P<0.05). On the first day after operation, the mean level of PTH in group C was lower than that in group A [(12.3±9.0) vs. (22.2±13.2) pg/ml, t=3.04, P=0.004] or group B [(12.3±9.0) vs. (20.0±14.1) pg/ml, t=2.09, P=0.043], and also the level of serum calcium in group C was lower than that in group A [(1.89±0.11) vs. (2.02±0.16) mmol/L, t=3.24, P=0.002] or group B [(1.89±0.11) vs. (2.01±0.15) mmol/L, t=2.72, P=0.010], with no significant difference in the mean levels of PTH or serum calcium between group A and group B (t=0.54, 0.29, respectively, both P>0.05). The incidences of permanent hypoparathyroidism/persistent hypocalcemia were 3.2% (1/31) in group A, 5.3% (1/19) in group B and 21.7% (5/23) in group C, and the incidence of group C was significantly higher than that (4%, 2/50) of both group A and group B (χ(2)=5.251, P=0.022). Conclusion: The postoperative parathyroid function and serum calcium level have different degrees of change and they are significantly associated with thyroidectomy approaches, the protection of parathyroid by oral endoscopic thyroidectomy and routine thyroidectomy can achieve the same effect, and is better than that of transthoracic thyroidectomy.
Assuntos
Hipocalcemia , Hipoparatireoidismo , Neoplasias da Glândula Tireoide , Adulto , Cálcio , Feminino , Humanos , Hipoparatireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/cirurgia , Hormônio Paratireóideo , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto JovemRESUMO
OBJECTIVE: This study is designed to investigate the role of miR-363-3p in the cancer development of glioma. PATIENTS AND METHODS: The expression of miR-363-3p in glioma and adjacent noncancerous tissue was measured using quantitative RT-PCR. The expression of a target gene of miR-363-3p, pyruvate dehydrogenase B (PDHB), was determined by Western blot. The level of miR-363-3p was increased or decreased by transfected with miR-363-3p mimic or miR-363-3p inhibitor, respectively. The impact of miR-363-3p on cell growth, apoptosis and invasion was determined by CCK-8 (Cell Counting Kit) assay, flow cytometry, and transwell assay. The role of PDHB in mediating the oncogenic activities was demonstrated by co-transfected PDHB vector and miR-363-3p mimic. RESULTS: Our results have shown that miR-3663-3p level was significantly higher in glioma tissue. Furthermore, miR-363-3p functions as onco-miRNA, promotes cell proliferation, protects against apoptosis, and enhances invasion by directly targeting PDHB. CONCLUSIONS: MiR-363-3p is an onco-miRNA, which can be considered as a potential therapeutic target in glioma.
Assuntos
Neoplasias Encefálicas/metabolismo , Proliferação de Células/fisiologia , Glioma/metabolismo , MicroRNAs/biossíntese , Complexo Piruvato Desidrogenase/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Feminino , Glioma/genética , Glioma/patologia , Humanos , MicroRNAs/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologiaRESUMO
OBJECTIVE: This study evaluates the value of continuous dynamic monitoring of intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage to predict early postoperative complications. PATIENTS AND METHODS: Data from 80 patients treated in our hospital from February 2014 to February 2015 were analyzed. The patients all underwent decompressive craniectomies, and their ICP changes were monitored invasively and continuously for 1 to 7 days after surgery. The average blood loss during surgery for the group of patients was 65.3 ± 12.4 ml and the mean GCS score 8.7 ± 2.4. Cases were divided into three groups according to ICP values to compare early postoperative complications of the groups: a normal and mildly increased group (51 cases), a moderately increased group (19 cases) and a severely increased group (10 cases). RESULTS: To validate the analysis we first showed that comparisons among groups based on gender, age, systolic pressure, diastolic pressure, bleeding time, blood loss, operation time, craniectomy localization, and preoperative mannitol dosage yielded no statistically significant differences. In contrast, the following comparisons produced statistically significant differences: the comparison of postoperative Glasgow Coma Scale (GCS) scores showing that the lower intracranial pressure, the higher the GCS score; the postoperative rehemorrhage, cerebral edema and death ratios showing the higher the intracranial pressure, the higher the rehemorrhage ratio; the average ICP and the time to occurrence of rehemorrhage, cerebral edema or cerebral infarction, showing the relationship between the average ICP and the time to a complication. Patients with higher ICP averages suffered a complication of rehemorrhage within the first 9.6 ± 2.5 hours on average. Nevertheless, the comparison of GCS scores in those patients and the others showed no significant differences. CONCLUSIONS: Based on the findings, the dynamic monitoring of intracranial pressure can early and sensitively predict postoperative complications of patients with hypertensive cerebral hemorrhage, and guide the clinical intervention actively to improve the surgery outcome.
Assuntos
Hemorragia Intracraniana Hipertensiva/cirurgia , Pressão Intracraniana , Complicações Pós-Operatórias/epidemiologia , Lesões Encefálicas , Escala de Coma de Glasgow , Humanos , Resultado do TratamentoRESUMO
The effect of N-bromosuccinimide (NBS) on the activity of Escherichia coli arginyl-tRNA synthetase (ArgRS) was studied. The results showed that only one tryptophan residue was easy of access to the reagent and was closely related to enzyme activity. When all the five tryptophan residues in ArgRS were changed via site-directed mutagenesis singly into Ala, the aminoacylation activity of the Trp162 mutated enzyme decreased seriously, while the other four mutant enzymes retained almost the same activity as the native one. The oxidation of the five mutant enzymes with NBS demonstrated that only the mutation of Trp162 resulted in the loss of sensitivity to the reagent. These results strongly suggest that Trp162 is more accessible to NBS and is related to enzyme activity. Furthermore, the far-UV CD spectroscopy of the mutant enzyme ArgRS162WA showed little change in its secondary structure. Finally, studies on the kinetics of the mutant enzyme ArgRS162WA in aminoacylation reaction showed that the reduction in activity could be attributed to the decrease in the values of kcat and kcat/Km for arginine. The thermodynamic calculation indicates that this mutation causes a decrease of the binding energy by 2.7 kJ/mol. Our data suggest that Trp162 is involved in the binding of arginine and in the transition state stabilization.
Assuntos
Arginina-tRNA Ligase/química , Escherichia coli/enzimologia , Triptofano/química , Acilação , Proteínas de Bactérias/química , Bromosuccinimida/farmacologia , Dicroísmo Circular , Fluorescência , Cinética , Mutagênese Sítio-Dirigida/genética , Oxirredução , Ligação Proteica/genética , Estrutura Secundária de Proteína , TermodinâmicaRESUMO
OBJECTIVE: To discuss the expression features of serum cystatin C, and homocysteine in patients of Parkinson's disease (PD) with mild cognitive impairment. PATIENTS AND METHODS: Patients with PD from the neurology department of the Central Hospital of Xuzhou from august 2012 to august 2014 were enrolled in this study. The Hoehn-Yahr (H&Y) grading rating scale was used to rate the degree of severity of PD, and the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) rating scale was used to rate and group their cognitive impairment, test the level of the serum cystatin C (CysC) and homocysteine (HCY) and their variations after treatment with vitamin B and folic acid. RESULTS: (1) The CysC and HCY in the PD group was higher than that in the normal control (p<0.05); (2) As the H&Y rating upgraded, the CysC and HCY in the PD group gradually increased with the progression of the disease (p<0.05); (3) The level of CysC and HCY in the PD-mild cognitive impairment (MCI) group increased significantly compared with those in the PD group (p<0.05) The correlation analysis showed that there was significant positive correlation between CysC and HCY. (4) After treatment with vitamin B and folic acid, the CysC, and HCY levels were lower than before, but the grades of the repetition measurement scale, MMSE and MoCA had no significant improvement (p>0.05). CONCLUSIONS: A high level of CysC and HCY might be involved in the development of Parkinson disease. Their expression levels were higher in the PD patients with mild cognitive dysfunction and both showed a remarkably positive correlation.
Assuntos
Transtornos Cognitivos/etiologia , Cistatina C/metabolismo , Homocisteína/metabolismo , Doença de Parkinson/metabolismo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A previous study has shown that UV activates the PI3K/AKT cell survival pathway while inducing cell death in human skin in vivo and cultured human keratinocytes in vitro, and yet the upstream pathway leading to the activation of AKT has not been thoroughly investigated. In this study we found that UV-induced phosphorylation of p38 and AKT in a time-dependent manner. The phosphorylation of p38 started at 5 min post UV irradiation, peaked at about 30 min, and remained elevated up to 2 h. The phosphorylation of AKT started at 15 min post UV treatment, peaked at about 1 h, and remained elevated up to 2 h. We also found that H2O2 induced phosphorylation of p38 and AKT in a time- dependent manner. Pretreatment with NAC abolished UV-induced AKT phosphorylation, suggesting the involvement of reactive oxygen species in AKT activation. Interestingly, SB203085, a known p38 inhibitor, had partially inhibited UV-induced AKT phosphorylation. Further studies showed that cytokines such as TNF-alpha and IL-1beta induced AKT phosphorylation in a time-dependent manner. Pretreatment with SB203085 inhibited IL-1beta-induced p38 and AKT phosphorylation. Collectively, our data suggest that UV activation of PI 3-kinase/AKT pathway is initiated by ROS and prolonged by feedback activation of p38 induced by released cytokines in response to UV irradiation in cultured human keratinocytes.
Assuntos
Retroalimentação Fisiológica/fisiologia , Interleucina-1/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Apoptose/efeitos da radiação , Western Blotting , Sobrevivência Celular , Células Cultivadas , Cromonas/farmacologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Inibidores Enzimáticos/farmacologia , Humanos , Imidazóis/farmacologia , Interleucina-1/antagonistas & inibidores , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Piridinas/farmacologia , Transdução de Sinais , Raios Ultravioleta , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
Oncogenes and N-acetylglucosaminyltransferase (GnT-V) are both commonly associated with carcinogenesis and metastasis. In order to elucidate the relationship between oncogenes and GnT-V, two oncogenes, H-ras and v-sis/PDGF (platelet-derived growth factor), were selected, and the effects of their overexpression on GnT-V in 7721 human hepatocarcinoma cells were investigated. The results showed that the over expression of H-ras or v-sis/PDGF-B up-regulated the activities of GnT-V to various degrees in the transfected cells. In H-ras- and PDGF-B-overexpressing cells, the activity of GnT-V was up-regulated to double the normal value. The transient expression of v-sis, which produces a protein almost identical to PDGF-B, stimulated the GnT-V activity by 80.3%, and the effect was more pronounced (increased by 182.5%) in 7721 cells with stable expression of v-sis. The stimulating effect was entirely abolished by treatment with PDGF-B antibody. The staining of asparagine-linked glycans (N-glycans) in the H-ras- and v-sis-overexpressing 7721 cells was intensified when horseradish peroxidase-labeled leucoagglutinating phytohemogglutinin was used as a probe, indicating the increased content of beta1,6GlcNAc branching on the N-glycans. The enhancement of GnT-V mRNA expression was also observed in H-ras- and v-sis- overexpressing cells, indicating that H-ras and v-sis regulated GnT-V via the transcription of GnT-V mRNA and the synthesis of GnT-V protein. The cells overexpressing H-ras and v-sis displayed some changes in metastasis-related phenotypes, including acceleration of cell growth, decline of cell adhesion to fibronectin, and an increase of cell adhesion to laminin, as well as increased invasiveness through Matrigel. These results indicated that the alteration of cell adhesion and invasion induced by oncogenes is closely related to the up-regulation of GnT-V activity and its product, beta1,6GlcNAc branching in N-glycans on the cell surface.
Assuntos
Carcinoma Hepatocelular/genética , Genes ras/genética , Genes sis/genética , Neoplasias Hepáticas/genética , N-Acetilglucosaminiltransferases/genética , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/secundário , Adesão Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , N-Acetilglucosaminiltransferases/metabolismo , Invasividade Neoplásica , Fenótipo , Células Tumorais CultivadasRESUMO
Nanocrystallization during deformation of metallic glass at room temperature has significant implications to understand its deformation mechanism. We present here direct high-resolution transmission electron microscopy (HRTEM) observations of nanocrystallization in a Zr(55)AI(10)Ni(5)Cu(30) bulk metallic glass (BMG) fractured by uniaxial compression at room temperature. The formed nanocrystallites are Zr(2)Cu, with the average diameter of less than 10nm, and are distributed within the round-like regions of localized plastic deformation. We also show direct evidence of atomic neighbor distance increases associated with the shrinkage and broadening of diffused ring pattern from local deformed areas, which may enhance atomic mobility so that nanocrystallization occurred. Our results demonstrate that the origin of the room-temperature deformation of BMG can be attributed to the local atomic spacing increases induced by localization of plastic flow under uniaxial compression test.
RESUMO
AIM: To investigate the photodegradation kinetic characteristics of lomefloxacin hydrochloride aqueous solution. METHODS: The HPLC method was used to determine the photodegradation kinetic parameters of lomefloxacin hydrochloride aqueous solution (10 micrograms.mL-1) under various pH buffer solutions, various ionic strength of different ions and various dielectric constant conditions. RESULTS: With comparative regression analysis of linear fit, the photodegradation kinetic order of lomefloxacin hydrochloride aqueous solution was determined as n = 1. The lomefloxacin hydrochloride aqueous solution is most unstable at pH 5.08-9.40 and is relatively stable at pH 2.02-5.08 and 9.40-11.10. The higher the ionic strength in lomefloxacin hydrochloride aqueous solution, the higher the photodegradation kinetic rate constant is. The chloride ion has important effect on photodegradation in aqueous solution of lomefloxacin and results in producing chlorine derivative as the highest photodegradation product. As the dielectric constant of solution increased, the photodegradation kinetic rate constant was also increased. CONCLUSION: It was found that the photodegradation of lomefloxacin followed apparent first-order kinetics. The photodegradation kinetic rate was affected by pH remarkably and showed positive correlation with ionic strength and dielectric constant.
Assuntos
Anti-Infecciosos/química , Fluoroquinolonas , Quinolonas/química , Soluções Tampão , Descarboxilação , Concentração de Íons de Hidrogênio , Cinética , Fotoquímica , SoluçõesRESUMO
The effects of light, pH and ionic strength on the degradation of four fluoroquinolones (norfloxacin, NFX; ofloxacin, OFX; ciprofloxacin, CPX; lomefloxacin, LEMX) solutions were studied. Using 2(3) factorial experiment and F test, it was confirmed that the degradation of NFX, OFX, CPX and LEMX was affected very markedly by light, but almost not affected by the ionic strength of the solution. The degradation of OFX and CPX was affected very markedly by pH, but the degradation of NFX and LEMX was almost not affected by pH. The degradation of OFX and CPX was affected very markedly by the combined action of light and pH, but the degradation of NFX and LEMX was almost not affected by the combined action of light and pH.