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1.
PLoS One ; 18(1): e0278817, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36595551

RESUMEN

With the development of medical science, long noncoding RNA (lncRNA), originally considered as a noise gene, has been found to participate in a variety of biological activities. Several recent studies have shown the involvement of lncRNA in various human diseases, such as gastric cancer, prostate cancer, lung cancer, and so forth. However, obtaining lncRNA-disease relationship only through biological experiments not only costs manpower and material resources but also gains little. Therefore, developing effective computational models for predicting lncRNA-disease association relationship is extremely important. This study aimed to propose an lncRNA-disease association prediction model based on the weight matrix and projection score (LDAP-WMPS). The model used the relatively perfect lncRNA-miRNA relationship data and miRNA-disease relationship data to predict the lncRNA-disease relationship. The integrated lncRNA similarity matrix and the integrated disease similarity matrix were established by fusing various methods to calculate the similarity between lncRNA and disease. This study improved the existing weight algorithm, applied it to the lncRNA-miRNA-disease triple network, and thus proposed a new lncRNA-disease weight matrix calculation method. Combined with the improved projection algorithm, the lncRNA-miRNA relationship and miRNA-disease relationship were used to predict the lncRNA-disease relationship. The simulation results showed that under the Leave-One-Out-Cross-Validation framework, the area under the receiver operating characteristic curve of LDAP-WMPS could reach 0.8822, which was better than the latest result. Taking adenocarcinoma and colorectal cancer as examples, the LDAP-WMPS model was found to effectively infer the lncRNA-disease relationship. The simulation results showed good prediction performance of the LDAP-WMPS model, which was an important supplement to the research of lncRNA-disease association prediction without lncRNA-disease relationship data.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Masculino , Humanos , ARN Largo no Codificante/genética , Biología Computacional/métodos , MicroARNs/genética , Algoritmos , Simulación por Computador
2.
J Cardiothorac Surg ; 17(1): 36, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35292067

RESUMEN

OBJECTIVE: By analyzing the perioperative, postoperative complications and long-term overall survival time, we summarized the 8-year experience of minimally invasive McKeown esophagectomy for esophageal cancer in a single medical center. METHODS: This retrospective follow-up study included 1023 consecutive patients with esophageal cancer who underwent MIE-McKeown between Mar 2013 and Oct 2020. Relevant variables were collected and evaluated. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan-Meier method. RESULTS: For 1023 esophageal cancer undergoing MIE-McKeown, the main intraoperative complications were bleeding (3.0%, 31/1023) and tracheal injury (1.7%, 17/1023). There was no death occurred during operation. The conversion rate of thoracoscopy to thoracotomy was 2.2% (22/1023), and laparoscopy to laparotomy was 0.3% (3/1023). The postoperative morbidity of complications was 36.2% (370/1023), of which anastomotic leakage 7.7% (79/1023), pulmonary complication 13.4% (137/1023), chylothorax 2.3% (24/1023), and recurrent laryngeal nerve injury 8.8% (90/1023). The radical resection rate (R0) was 96.0% (982/1023), 30-day mortality was 0.3% (3/1023). For 1000 cases with squamous cell carcinoma, the estimated 3-year and 5-year overall survival was 37.2% and 17.8% respectively. In addition, neoadjuvant chemotherapy offered 3-year disease-free survival rate advantage in advanced stage patients (for stage IV: 7.2% vs. 1.8%). CONCLUSIONS: This retrospective single center study demonstrates that MIE-McKeown procedure is feasible and safe with low perioperative and postoperative complications' morbidity, and acceptable long-term oncologic results.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Neoplasias Esofágicas/patología , Esofagectomía/efectos adversos , Esofagectomía/métodos , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
3.
Yakugaku Zasshi ; 141(3): 415-426, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33116033

RESUMEN

Doxorubicin (DOX) is currently one of the most widely used and effective drugs for the treatment of breast cancer, but drug resistance in breast cancer often leads to poor efficacy. MicroRNAs (miRNAs) are involved in the development and progression of various tumors and increasing number of studies have confirmed that abnormal miR-520b expression is closely associated breast cancer. We analyzed the clinical features, including miR-520b, of 30 patients with breast cancer. Further, we analyzed the interaction between miR-520b and insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cell. miR-520b expression was significantly increased in chemotherapy-sensitive patients and was positively correlated with the chemotherapeutic efficacy in breast cancer. Cell proliferation assay confirmed that miR-520b promotes DOX-induced breast cancer cell apoptosis by regulating the PI3K/AKT signaling pathway. Moreover, bioinformatics method and dual luciferase reporter assay demonstrated that miR-520b negatively regulates IGF-1R, and IGF-1R overexpression and enhanced activity are closely associated with tumor development, progression, metastasis, and chemotherapy resistance. Similarly, cell proliferation assay showed that IGF-1R is negatively correlated with the efficacy of DOX chemotherapy and affects cell apoptosis mediated by the PI3K/AKT signaling pathway. On the contrary, miR-520b can downregulate the expression of IGF-1R. miR-520b increases DOX sensitivity and promotes cell apoptosis in breast cancer by inhibiting IGF-1R expression by the PI3K/AKT signaling pathway.


Asunto(s)
Antibióticos Antineoplásicos/metabolismo , Apoptosis/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Doxorrubicina/metabolismo , Resistencia a Antineoplásicos/genética , MicroARNs/genética , MicroARNs/metabolismo , Receptor IGF Tipo 1/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Regulación hacia Abajo/genética , Femenino , Expresión Génica/genética , Humanos , Células MCF-7 , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/genética
4.
J Zhejiang Univ Sci B ; 20(7): 576-587, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31168971

RESUMEN

OBJECTIVE: Apios americana, a plant used as a staple ingredient of native American diets, has various properties, including anti-cancer, anti-hyperglycemic, hypotensive, and anti-inflammatory activity. In Japan, Apios is used as a post-natal medication. After parturition, women undergo a period of recovery as they return to pre-pregnancy conditions. However, few health products that aid post-partum recovery are on the market. We explored whether Apios can accelerate the post-partum recovery process, in particular the involution of the uterus. METHODS: Female rats kept in individual cages were mated with two male rats, with the exception of the control group (female rats without mating, on basal diet; n=6). After delivery, rats were divided into five groups based on their diet: basal diet (model; n=6); basal diet+oral intake at 5.4 g/kg of Chanfukang granules (a Chinese patent medicine preparation for post-partum lochia) (positive; n=6); basal diet containing 10% Apios powder (low; n=6); basal diet containing 20% Apios powder (medium; n=6); basal diet containing 40% Apios powder (high; n=6). Five days later, uteri and spleens were weighed. Uterus and spleen indices for each rat were calculated by dividing visceral weight by the total weight. Hormone and cytokine concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Histological analysis of uteri was completed using hematoxylin and eosin (H&E) staining. Expression of matrix metalloproteinases and inhibitors in uteri was measured by western blotting. RESULTS: Our results showed that Apios treatment reduced the post-partum uterus index and regulated the hormone concentrations. Moreover, we found that the process of uterine involution was accelerated, based on morphological changes in the uterus. In addition, our results indicated that Apios alleviated the inflammatory response induced by the involution process. Transforming growth factor ß was also found to be regulated by Apios. There were significant downregulation of matrix metalloproteinases and upregulation of their inhibitors by Apios, which suggested that Apios increased the rate of the collagen clearance process. CONCLUSIONS: These results, based on experimental observations at the molecular and protein levels, verified our hypothesis that Apios can improve uterine involution, and demonstrated the potential application of Apios in post-partum care.


Asunto(s)
Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Fabaceae/química , Útero/efectos de los fármacos , Administración Oral , Animales , Citocinas/metabolismo , Femenino , Metaloproteinasas de la Matriz/metabolismo , Periodo Posparto , Polvos , Embarazo , Preñez , Ratas , Reproducción , Bazo/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo
5.
Onco Targets Ther ; 12: 11691-11700, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32021247

RESUMEN

INTRODUCTION: The breast cancer stem cells contribute to the initiation, progression, recurrence, metastasis as well as resistance of breast cancer. However, the mechanisms underlying the maintenance of breast cancer stemness have not been fully understood. MATERIALS AND METHODS: TCGA and GEO data were used for measuring miR-520b expression in breast cancer tissues. Kaplan-meier analysis was used for determining the relationship between miR-520b expression level and the prognosis of patients. Genetic manipulation was performed by lentivirus system and miR-520b inhibitor was used for knockdown of miR-520b. qRT-PCR and Western blot were employed to determine the mRNA and protein levels, respectively. The stemness and EMT (Epithelial to mesenchymal transition) were assessed by sphere-formation and transwell assay as well as the expression of the related markers. The target genes of miR-520b were identified using the online database starBase V3.0. RESULTS: miR-520b is upregulated in cancer tissues of breast cancer patients and predicts poor prognosis. Upregulation of miR-520b was found in breast cancer stem cells. Ectopic expression of miR-520b promotes the stemness of the breast cancer cells, conversely, depletion of miR-520b attenuates the stemness of these cells. miR-520b positively regulates Hippo/YAP signaling pathway and overexpression of LAST2 abolished the effect of miR-520b on the stemness of breast cancer cells. CONCLUSION: miR-520b promotes the stemness of breast cancer patients by activating Hippo/YAP signaling via targeting LATS2.

6.
J Dermatol ; 45(7): 867-870, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29740858

RESUMEN

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease characterized by hamartomas in multiple organ systems. This study was performed in one familial and two sporadic cases with TSC. Two novel mutations (c.1884_1887delAAAG and c.5266A>G) and two previously reported mutations (c.4258_4261delTCAG and c.1960G>C) were identified by direct DNA sequencing. Of the four mutations, c.1884_1887delAAAG and c.1960G>C were found in a family and identified in the same allele by TA cloning sequencing. However, c.1960G>C was reported to be non-pathogenic. Furthermore, correlations between genotypes and phenotypes of Chinese Han patients since 2014 were performed by paired χ2 -tests in our published work review, which has not been reported. The results showed that patients with TSC2 mutations had a higher frequency of mental retardation and there were no significant differences of seizures and skin lesions with TSC1 mutations. Genetically, they had a higher frequency of familial inheritance.


Asunto(s)
Discapacidad Intelectual/genética , Convulsiones/genética , Esclerosis Tuberosa/genética , Proteínas Supresoras de Tumor/genética , Adulto , Pueblo Asiatico/genética , Encéfalo/diagnóstico por imagen , Niño , Análisis Mutacional de ADN , Electroencefalografía , Exones/genética , Femenino , Genotipo , Humanos , Discapacidad Intelectual/diagnóstico , Mutación , Fenotipo , Convulsiones/diagnóstico , Piel/patología , Tomografía Computarizada por Rayos X , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/patología , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteína 2 del Complejo de la Esclerosis Tuberosa
7.
Zhongguo Gu Shang ; 31(2): 186-189, 2018 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-29536694

RESUMEN

OBJECTIVE: To discusses the clinical effects of arthroscopy combined with minimally invasive percutaneous plate osteosynthesis(MIPPO) technology in treating Schatzker IV tibial plateau fractures. METHODS: From January 2012 to January 2016, 19 patients with Schatzker type IV tibial plateau fractures were treated with arthroscopy combined with minimally invasive technique including 12 males and 7 females with an average age of 46.5 years old ranging from 19 to 78 years old. Patients were suffering knee pain, swelling, flexion and extension limited, and other symptoms preoperative. Patients were followed up and assessed by Rasmussen knee function score. RESULTS: No infection, traumatic arthritis, and knee joint valgus occurred after operation. Nineteen cases were followed up for 12 to 24 months with an average of 18.6 months. Fracture healing time was 3 to 5 months with an average of 3.8 months. The knee pain and limited mobility improved significantly. The range of autonomic movement of joints was from 90 to 136 degrees. According to Rasmussen functional score criteria, the total score was 27.00±2.49, the result was excellent in 16 cases, good in 2 cases, fair in 1 case. CONCLUSIONS: Arthroscopic treatment for Schatzker type IV tibial plateau fractures combined with MIPPO can simultaneously treat internal structural injuries such as meniscus and other knee joints, with less trauma, fewer complications, and faster joint function recovery, but we must strictly grasp surgical indications and avoid expanding injuries.


Asunto(s)
Artroscopía , Fijación Interna de Fracturas , Fracturas de la Tibia/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tibia , Resultado del Tratamiento , Adulto Joven
8.
Oncotarget ; 8(33): 54694-54707, 2017 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-28903375

RESUMEN

Yin Yang 2 (YY2) is a multifunctional zinc-finger transcription factor that belongs to YY family. Unlike the well-characterized YY1, our understanding regarding the biological functions of YY2 is still very limited. Here we found for the first time that in contrast to YY1, which had been reported to be oncogenic, the expression level of YY2 in tumor cells and/or tissues was downregulated compared with its expression level in the normal ones. We also demonstrated that YY2 exerts biological function contrary to YY1 in cell proliferation. We elucidated that YY2 positively enhances p21 expression, and concomitantly, its silencing promotes cells to enter G2/M phase and enhances cell proliferation. Furthermore, we found that YY2 regulation on p21 occurs p53-dependently. Finally, we identified a novel YY2 binding site in the promoter region of tumor suppressor p53. We found that YY2 binds to the p53 promoter and activates its transcriptional activity, and subsequently, regulates cell cycle progression via p53/p21 axis. Taken together, our study not only identifies YY2 as a novel tumor suppressor gene that plays a pivotal role in cell cycle regulation, but also provides new insights regarding the regulatory mechanism of the conventional p53/p21 axis.

9.
J Zhejiang Univ Sci B ; 18(7): 615-625, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28681586

RESUMEN

The aim of this study was to research the changes in cytotoxicity and antibacterial properties after silver nanoparticles (AgNPs) were incorporated into the surface coating of dental alloys. AgNPs were attached to cobalt chromium alloys and pure titanium using a hydrothermal method, according to the reaction: AgNO3+NaBH4→ Ag+1/2H2+1/2B2H6+NaNO3. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate the cytotoxicity of the alloys when in contact with osteogenic precursor cells (MC3T3-E1) from mice and mesenchymal stem cells (BMSC) from rats. The antibacterial properties of dental alloys incorporating three different concentrations (10, 4, and 2 µmol/L) of AgNPs were tested on Staphylococcus aureus (SA) and Streptococcus mutans (MS). High cytotoxicity values were observed for all dental alloys that contained 0% of AgNPs (the control groups). The incorporation of AgNPs reduced cytotoxicity values. No significant difference was observed for antibacterial performance when comparing dental alloys containing AgNPs to the respective control groups. The results demonstrated that the cobalt chromium alloys and pure titanium all had cytotoxicity to MC3T3-E1 and BMSC and that the incorporation of AgNPs could reduce this cytotoxicity. The concentrations of AgNPs adopted in this study were found to have no antibacterial action against SA or MS.


Asunto(s)
Antibacterianos/farmacología , Aleaciones Dentales/química , Nanopartículas del Metal/química , Plata/química , Staphylococcus aureus/efectos de los fármacos , Células 3T3 , Animales , Células Madre Mesenquimatosas/citología , Ratones , Microscopía Electrónica de Rastreo , Ratas , Streptococcus mutans/efectos de los fármacos
10.
J Zhejiang Univ Sci B ; 17(6): 437-46, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27256677

RESUMEN

BACKGROUND: Myricetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. OBJECTIVE: This study was undertaken to investigate the effect of myricetin on high-fat diet (HFD)-induced obesity in C57BL/6 mice. RESULTS: Administration of myricetin dramatically reduced the body weight of diet-induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly decreased in myricetin-treated mice. Moreover, obesity-associated oxidative stress (glutathione peroxidase (GPX) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA)) and inflammation (tumor necrosis factor-α (TNF-α)) were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of myricetin against HFD-induced obesity in mice appeared to be partially mediated through the down-regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP-1c). CONCLUSIONS: Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications.


Asunto(s)
Flavonoides/farmacología , Obesidad/prevención & control , Estrés Oxidativo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Animales , Dieta Alta en Grasa , Grasa Intraabdominal/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacología , Factor de Necrosis Tumoral alfa/sangre
11.
Asian Pac J Allergy Immunol ; 34(2): 109-14, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27007831

RESUMEN

BACKGROUND: Recent genome-wide association studies (GWAS) and a meta-analysis of GWAS for atopic dermatitis (AD) have identified some AD genetic loci in European and Japanese populations. OBJECTIVE: To investigate whether some novel susceptibility loci are associated with AD in the Chinese Han population. METHODS: We first selected eight novel susceptibility loci to replicate in 2,205 AD patients and 2,116 healthy controls using the Sequenom platform. Data were analyzed with PLINK 1.07 software. RESULTS: We found that rs12634229 (3q13.2), rs7927894 (11p13.5) and rs878860 (11p15.4) showed a slight association with AD (P = 0.012, P = 0.033, P = 0.020, respectively); rs6780220 (3p21.33) was preferentially related to AD with keratosis pilaris, but did not reach the threshold of significance after correction. The frequency of rs7927894 allele T was significantly different between AD patients with a positive and negative family history of atopy. CONCLUSION: The loci rs7927894 (11p13.5) are related to AD with a positive family history of atopy in Chinese Han population, providing novel insight into the genetic pathogenesis of AD.


Asunto(s)
Pueblo Asiatico/genética , Cromosomas Humanos Par 11 , Dermatitis Atópica/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , China/epidemiología , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/etnología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido , Masculino , Linaje , Fenotipo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto Joven
12.
Zhongguo Gu Shang ; 28(8): 726-9, 2015 Aug.
Artículo en Chino | MEDLINE | ID: mdl-26502524

RESUMEN

OBJECTIVE: To discuss the clinical significance of the reduction and fixation for femoral lesser trochanteric fragment in treating the femoral comminuted intertrochanteric fractures. METHODS: From January 2012 to December 2013,32 patients with intertrochanteric fractures were treated by surgery, and self-designed reduction fixators were used in the patients for the fixation of lesser trochanter of femur. There were 11 males and 21 females, ranging in age from 45 to 81 years old with an average of 64 years old. According to the Evans typing, 12 cases were type II, 13 cases were type III and 7 cases were type IV. Simple lag screw fixed in 19 cases and steel wire fixed in 13 cases. Hip joint function was evaluated according Harris score and the complications such as coxa adducta,cutting of femoral head and neck,implants breakage were observed. RESULTS: Thirty-two patients were followed up from 9 to 24 months with an average of 13 months. Coxa adducta occurred in 1 case,no cutting of femoral head and neck occurred and implants breakage were found. The mean Harris score was 91.80 ± 3.05 in 32 patients. CONCLUSION: The reconstruction and fixation for the posterior medial bone cortex continuity is a key factor on affect the stability of femoral intertrochanteric fracture. Self-designed reduction fixators can effective reduce and fix the lesser trochanter of femur, it has advantage of fast reduction and fixation, and simple operation.


Asunto(s)
Fijación Interna de Fracturas/instrumentación , Fracturas de Cadera/cirugía , Anciano , Anciano de 80 o más Años , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad
13.
Am J Cancer Res ; 5(3): 1234-50, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26046002

RESUMEN

Wilms' tumor gene 1 (WT1) single nucleotide polymorphism (SNP), rs16754, has been considered as an independent prognostic factor in patients with acute myeloid leukemia and renal cell carcinoma. However, its biological role in breast cancer has not been reported. To test whether WT1 SNPs can be used as a molecular marker in order to improve the risk stratification of breast cancer, we performed a case-control study including 709 female sporadic breast cancer patients and 749 female healthy control subjects in the Southeast China. Five WT1 SNPs (rs16754, rs3930513, rs5030141, rs5030317, rs5030320) were selected and determined by polymerase chain reaction-ligase detection reaction to assess their associations with breast cancer risk. Results showed the distributions of the alleles of these WT1 SNPs were consistent with data from Chinese population as suggested by the International HapMap Project. Individuals with the minor alleles of rs16754, rs5030317 and rs5030320 showed a significant decrease of breast cancer risk in codominant model (OR = 0.6370, 95% CI: 0.4260-0.9520 for rs16754; OR = 0.5940, 95% CI: 0.3890-0.9070 for rs5030317; OR = 0.5870, 95% CI: 0.3850-0.8960 for 5030320, respectively) and recessive model. Stratified analyses showed the protective effects were more evident in the subjects with age ≤ 50 years or in pre-menopausal status. To explore the potential mechanism, we conducted bioinformatics genotype-phenotype correlation analysis, and found that the mRNA expression level for homozygous rare allele of WT1 gene was lower than that in wild-type and heterozygous group (P = 0.0021) in Chinese population. In summary, our findings indicated that minor alleles of rs16754, rs5030317 and rs5030320 are associated with reduced risk of breast cancer, suggesting that WT1 SNPs may be a potential biomarker of individualized prediction of susceptibility to breast cancer. However, large prospective and molecular epidemiology studies are needed to verify this correlation and clarify its underlying mechanisms.

14.
Int J Clin Exp Pathol ; 7(2): 728-32, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24551296

RESUMEN

Disseminated superficial actinic porokeratosis (DSAP) is the most common form of porokeratosis and a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. Recently, the mevalonate kinase (MVK) gene has been identified as a candidate gene responsible for DSAP and multiple mutations have been reported. Here, we report identification of a novel missense mutation in the MVK gene in a Chinese family with DSAP. A 50-year-old male was diagnosed as proband of DSAP based on the clinical and histological findings, which show numerous hyperpigmented macules by physical examination and cornoid lamella by skin biopsy. Similar skin symptoms were also observed in his father, who died many years ago. We prepared genomic DNA from the proband, unaffected individuals from his family members, as well as 100 unrelated healthy controls. PCR was then conducted using the above genomic DNA as template and the MVK gene-specific primers. The PCR product was subjected to direct sequencing and the sequence was compared to that of MVK gene within the NCBI database. We detected a heterozygous C to G transition at nucleotide 643 in exon 7 of MVK gene of the proband. This will result in an amino acid change at codon 215 (P.Arg215Gly.), which is from an arginine codon (CGA) to a Glycine codon (GGA). We did not detect any mutation in the unaffected family members or the 100 unrelated healthy controls, demonstrating that this is a novel missense mutation in MVK gene and therefore, contributes to the molecular diagnosis of DSAP.


Asunto(s)
Pueblo Asiatico/genética , Análisis Mutacional de ADN , Mutación Missense , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Poroqueratosis/genética , Biopsia , Estudios de Casos y Controles , China , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Poroqueratosis/enzimología , Poroqueratosis/etnología , Poroqueratosis/patología , Valor Predictivo de las Pruebas , Piel/patología
15.
J Invest Dermatol ; 134(2): 359-365, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23897274

RESUMEN

Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To further advance gene discovery, we extended our genome-wide association study data set of 1,139 cases and 2,234 controls and replicated two independent cohorts of 7,200 cases and 10,491 controls. We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (Pcombined=1.83 × 10(-13), odds ratio=1.16) and validated four previously reported genes: IL28RA, NFKBIA, TRAF3IP2, and CARD14 (9.74 × 10(-11)P9.37 × 10(-5)), which confirmed the involvement of the nuclear factor-κB signaling pathway in psoriasis pathogenesis. LNPEP, also named insulin-responsive aminopeptidase, was identified as an angiotensin IV receptor. Protein function prediction suggested that this missense variant of LNPEP was most likely deleterious. Expression analysis showed that LNPEP was significantly downregulated in psoriatic lesions compared with the control skin (P=1.44 × 10(-6)) and uninvolved patient skin (P=2.95 × 10(-4)). Pathway analysis indicated that LNPEP was involved in the renin-angiotensin system, which also has a key role in cardiovascular disease and diabetes. These results provided genetic evidence that psoriasis might share common mechanisms with hypertension and diabetes, which was consistent with clinical observations. Our study identified a genetic susceptibility factor and provided genetic evidence of insight into psoriasis pathogenesis with the involvement of the renin-angiotensin system pathway.


Asunto(s)
Cistinil Aminopeptidasa/genética , Mutación Missense , Psoriasis/epidemiología , Psoriasis/genética , Proteínas Adaptadoras Transductoras de Señales , Adolescente , Adulto , Pueblo Asiatico/genética , Pueblo Asiatico/estadística & datos numéricos , Proteínas Adaptadoras de Señalización CARD/genética , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Guanilato Ciclasa/genética , Humanos , Proteínas I-kappa B/genética , Interleucinas/genética , Masculino , Proteínas de la Membrana/genética , Inhibidor NF-kappaB alfa , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/genética , Población Blanca/genética , Población Blanca/estadística & datos numéricos , Adulto Joven
16.
Yao Xue Xue Bao ; 48(2): 187-92, 2013 Feb.
Artículo en Chino | MEDLINE | ID: mdl-23672014

RESUMEN

The synthetic biology matures to promote the heterologous biosynthesis of the well-known drug paclitaxel that is one of the most important and active chemotherapeutic agents for the first-line clinical treatment of cancer. This review focuses on the construction and regulation of the biosynthetic pathway of paclitaxel intermediates in both Escherichia coli and Saccharomyces cerevisiae. In particular, the review also features the early efforts to design and overproduce taxadiene and the bottleneck of scale fermentation for producing the intermediates.


Asunto(s)
Alquenos/metabolismo , Diterpenos/metabolismo , Escherichia coli/metabolismo , Paclitaxel/biosíntesis , Saccharomyces cerevisiae/metabolismo , Biología Sintética , Alquenos/química , Antineoplásicos Fitogénicos/biosíntesis , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/metabolismo , Vías Biosintéticas , Diterpenos/química , Fermentación , Ingeniería Metabólica , Paclitaxel/química , Paclitaxel/metabolismo , Profármacos
17.
J Med Genet ; 49(9): 563-8, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22972947

RESUMEN

BACKGROUND: Punctate palmoplantar keratoderma (PPPK) is a rare autosomal dominant skin disorder characterised by numerous hyperkeratotic papules irregularly distributed on the palms and soles. To date, no causal gene for this disease has been identified. METHODS: We performed exome sequencing analysis of four affected individuals and two unaffected controls from one Chinese PPPK family where disease locus was mapped at 8q24.13-8q24.21 by our previous linkage analysis. RESULTS: We identified a novel heterozygous mutation in COL14A1 gene (c.4505C→T (p.Pro1502Leu)), which located within the linkage region that we previously identified for PPPK. The mutation was shared by the four affected individuals, but not for the two controls of the family. Sanger sequencing confirmed this mutation in another four cases from this family. This mutation was invisible in the normal controls of this family as well as the additional 676 unrelated normal controls and 781 patients with other disease. The shared COL14A1 mutation, p.Pro1502Leu, is a missense substitution at a highly conserved amino acid residue across multiple species. CONCLUSIONS: The power of combining exome sequencing and linkage information in the study of genetics of autosomal dominant disorders, even in simplex cases, has been demonstrated. Our results suggested that COL14A1 would be a casual gene for PPPK, which was helpful for advancing us on understanding of the pathogenesis of PPPK.


Asunto(s)
Pueblo Asiatico/genética , Colágeno/genética , Análisis Mutacional de ADN/métodos , Exoma/genética , Glicoproteínas/genética , Queratodermia Palmoplantar/genética , Mutación/genética , Adulto , Secuencia de Aminoácidos , China , Femenino , Genoma Humano/genética , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Polimorfismo de Nucleótido Simple/genética
18.
J Sci Food Agric ; 92(13): 2668-71, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22696430

RESUMEN

BACKGROUND: Recently, food-grade microemulsions have been of increasing interest to researchers and have shown great potential in industrial applications. In this study a food-grade water-dilutable microemulsion system with cassia oil as oil, ethanol as cosurfactant, Tween 20 as surfactant and water was developed and its antifungal activity in vitro and in vivo against Geotrichum citri-aurantii was assessed. RESULTS: The phase diagram results confirmed the feasibility of forming a water-dilutable microemulsion based on cassia oil. One microemulsion formulation, cassia oil/ethanol/Tween 20 = 1:3:6 (w/w/w), was selected with the capability to undergo full dilution with water. The average particle size was 6.3 nm. The in vitro antifungal experiments showed that the microemulsion inhibited fungal growth on solid medium and prevented arthroconidium germination in liquid medium and that cassia oil had stronger activity when encapsulated in the microemulsion. The in vivo antifungal experiments indicated that the water-dilutable microemulsion was effective in preventing postharvest diseases of citrus fruits caused by G. citri-aurantii. CONCLUSION: The results of this study suggest a promising utilisation of water-dilutable microemulsions based on essential oils for the control of postharvest diseases.


Asunto(s)
Antifúngicos/farmacología , Cassia/química , Citrus/microbiología , Frutas/microbiología , Geotrichum/efectos de los fármacos , Enfermedades de las Plantas/prevención & control , Aceites de Plantas/farmacología , Dieta , Emulsiones , Etanol , Geotrichum/crecimiento & desarrollo , Tamaño de la Partícula , Enfermedades de las Plantas/microbiología , Polisorbatos , Tensoactivos , Agua
19.
Zhongguo Gu Shang ; 25(3): 251-5, 2012 Mar.
Artículo en Chino | MEDLINE | ID: mdl-22712381

RESUMEN

OBJECTIVE: To investigate the application of transpedicular porking repositor, thread device and transpedical interbody bone grafting apparatus in the treatment of thoracolumbar spinal fracture. METHODS: From March 2008 to March 2011, 17 males and 15 females with thoracolumbar spinal fracture were treated by using self-designed transpedicular porking reposito, thread device and transpedical interbody bone grafting apparatus. The average age was 39.4 years (ranged from 25 to 65 years). All the cases were checked by X-ray and CT before and one week, one year after operation, removal of internal fixation. The angle of injured vertebral sagittal, cobbs angle and injured vertebral height were measured. RESULTS: All patients were followed up, and the duration ranged for 14 to 21 months (averaged 16 months). The content of following up included loss of ithycyphos and height of spinal, fracture healing and implant fixation. Nerve vascular complication caused by implantation didn't occurred; interverbral body fusion was good. The results preoperative, 1 week and year postoperative and 3 months after taking out the internal fixation showed injured spinal height maintained well, loss and collapse of height and angle did not occurred. CONCLUSION: Treating thoracolumbar spinal fracture can obtained satisfactory effects by using transpedicular porking repositor, thread device and transpedical interbody bone grafting apparatus. It has advantages of minimal invasive, and can promote fracture healing earlier, recover spinal height, rebuild stability of spinal, prevent loss and collapse of vertebral body height to avoid anterior lumbar surgery on the late stage.


Asunto(s)
Vértebras Lumbares/cirugía , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/cirugía , Adulto , Anciano , Trasplante Óseo , Femenino , Fijación Interna de Fracturas , Humanos , Vértebras Lumbares/lesiones , Masculino , Persona de Mediana Edad , Vértebras Torácicas/lesiones
20.
Zhongguo Gu Shang ; 24(10): 869-72, 2011 Oct.
Artículo en Chino | MEDLINE | ID: mdl-22097141

RESUMEN

OBJECTIVE: To explore the diagnosis and treatment of tarsometatarsal joint complex injury (TJC). METHODS: From January 2007 to January 2009,16 patients with tarsometatarsal joint complex injury were treated with open reduction and internal fixation. There were 12 males and 4 females, ranging in age from 21 to 45 years with an average of 34.1 years. Seven cases were left and 9 cases were right and all injuries caused by direct violence. Four cases caused by traffic accident 5 by fall from high and 7 by crush injury. Intercuneiform dislocation were in 11 cases, naviculocuneiform joint dislocation in 3 cases and cuboid fracture in 2 cases. All the cases were three column injuries. According to the situation of exploring and the stability, screw fixation was used for intertarsal joint, internal and middle column tarsometatarsal joint, the Kirschner wire fixation for external column and miniature plate fixation for comminuted fracture of metatarsal bones and compressible fracture of cuboid. The criteria of the AOFAS Foot and Ankle Surgery by the United States Association of ankle-rear foot functional scale was used to evaluate the clinical effect. RESULTS: All the patients were followed up,the duration ranged from 6 to 18 months(averaged 12.6 months). According to the score system of AOFAS,the total score was (74.6+/-10.4 ) points, including pain items of (29.3+/-5.9), the score of functional items of (32.4+/-5.6) points, and power lines of (12.9+/-2.6). All the incisions were primarily healed without infection, skin necrosis,fixture broken or loosen. Three cases received arthrodesis due to osteoarthritis. Four cases were followed up continually because they only had the radiologic osteoarthritis without pain. CONCLUSION: Anatomical reduction and stable fixation is the key point of the treatment of tarsometatarsal joint complex injury. Open reduction and internal fixation at the first stage is good for secondary arthrodesis.


Asunto(s)
Huesos Metatarsianos/lesiones , Articulaciones Tarsianas/lesiones , Adulto , Femenino , Fijación Interna de Fracturas , Humanos , Masculino , Huesos Metatarsianos/cirugía , Persona de Mediana Edad , Articulaciones Tarsianas/cirugía
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