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1.
BMC Pediatr ; 24(1): 157, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443865

RESUMEN

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.


Asunto(s)
Displasia Broncopulmonar , Corioamnionitis , Lesión Pulmonar , Síndrome de Dificultad Respiratoria del Recién Nacido , Recién Nacido , Femenino , Embarazo , Lactante , Humanos , Corioamnionitis/epidemiología , Recien Nacido Prematuro , Inflamación , Displasia Broncopulmonar/epidemiología , Displasia Broncopulmonar/etiología , Síndrome de Dificultad Respiratoria del Recién Nacido/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología
2.
Microb Cell Fact ; 22(1): 225, 2023 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-37924089

RESUMEN

Lacticaseibacillus is one of the predominant microorganisms in gut from human and animal, and the lacticaseibacillus have effective applications against the viral diarrhea of piglets in the farm. However, the function and the concrete cell single pathways of the active ingredient from lacticaseibacillus was not clear within anti-infection in the postbiotics research. Here, we compared the biological function of extracellular polysaccharides (EPS) purified from lacticaseibacillus casei (L. casei) and gene editing lacticaseibacillus casei with the CRISPER-Cas9 technology, which were with the ability of antioxidation and anti-inflammation, and the EPS could also inhibit the ROS production within the Porcine Small Intestinal Epithelial Cells-J2 (IPEC-J2). Interestingly, we found that both of EPS and genome editing lacticaseibacillus casei could specifically target the IFN-λ expression in the IPEC-J2, which was beneficial against the PEDV infection in the virus replication and production with the qRT-PCR and indirect immunofluorescence methods. Finally, the STAT3 cell single pathway was stimulated to transcribe IFN-λ with the EPS to elucidate the detailed mechanism of activating type III IFN signals receptor of IL-10R2, which play the function between anti-inflammation and anti-virus in the PEDV infection. Taken together, our research linked a postbiotics of EPS with the antiviral infection of PEDV, which suggest that the lacticaseibacillus itself still have displayed the potential immunomodulatory activities, and highlight the immunomodulatory potential of EPS-producing microbes.


Asunto(s)
Infecciones por Coronavirus , Virus de la Diarrea Epidémica Porcina , Humanos , Animales , Porcinos , Virus de la Diarrea Epidémica Porcina/genética , Lacticaseibacillus , Edición Génica , Infecciones por Coronavirus/veterinaria , Células Epiteliales
3.
Molecules ; 28(10)2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37241840

RESUMEN

Asthma is a common chronic disease that is characterized by respiratory symptoms including cough, wheeze, shortness of breath, and chest tightness. The underlying mechanisms of this disease are not fully elucidated, so more research is needed to identify better therapeutic compounds and biomarkers to improve disease outcomes. In this present study, we used bioinformatics to analyze the gene expression of adult asthma in publicly available microarray datasets to identify putative therapeutic molecules for this disease. We first compared gene expression in healthy volunteers and adult asthma patients to obtain differentially expressed genes (DEGs) for further analysis. A final gene expression signature of 49 genes, including 34 upregulated and 15 downregulated genes, was obtained. Protein-protein interaction and hub analyses showed that 10 genes, including POSTN, CPA3, CCL26, SERPINB2, CLCA1, TPSAB1, TPSB2, MUC5B, BPIFA1, and CST1, may be hub genes. Then, the L1000CDS2 search engine was used for drug repurposing studies. The top approved drug candidate predicted to reverse the asthma gene signature was lovastatin. Clustergram results showed that lovastatin may perturb MUC5B expression. Moreover, molecular docking, molecular dynamics simulation, and computational alanine scanning results supported the notion that lovastatin may interact with MUC5B via key residues such as Thr80, Thr91, Leu93, and Gln105. In summary, by analyzing gene expression signatures, hub genes, and therapeutic perturbation, we show that lovastatin is an approved drug candidate that may have potential for treating adult asthma.


Asunto(s)
Asma , Perfilación de la Expresión Génica , Humanos , Adulto , Perfilación de la Expresión Génica/métodos , Simulación del Acoplamiento Molecular , Asma/tratamiento farmacológico , Asma/genética , Genes Reguladores , Biología Computacional/métodos , Lovastatina , Redes Reguladoras de Genes , Mapas de Interacción de Proteínas/genética
4.
Pak J Med Sci ; 39(5): 1296-1300, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680810

RESUMEN

Objective: To investigate the safety and outcomes of endovascular embolization and craniotomy clipping in the treatment of cerebral aneurysms. Methods: We collected the clinical data of 106 patients with cerebral aneurysm who underwent surgical treatment (endovascular embolization, Group-A, n=55; craniotomy clipping, Group-B, n=51) in the First People's Hospital of Yichang from January 2020 to May 2021. We compared surgical treatment indexes, treatment costs, neurological function before and after the treatment, incidence of postoperative complications and the prognosis after one-year follow-up between the two groups. Results: Endovascular embolization (Group-A) was associated with a shorter mean operation time and hospital stay, a lower mean intraoperative bleeding amount, and a higher mean treatment cost than craniotomy clipping (Group-B) (P<0.05). Compared with the pre-operative neurological function scores, the scores of both groups decreased after the surgery, and the mean post-operative score of Group-A was significantly lower than that of Group-B (P<0.05). Compared with Group-B , patients in Group-A had a lower overall complication rate (P < 0.05. Higher proportion of patients in Group-A had a good prognosis (P < 0.05). Conclusion: Endovascular embolization for the treatment of cerebral aneurysms is safe as it can shorten the operation time and hospital stay, reduce the incidence of neurological injury and complications, and have a favorable prognosis. However, the treatment is more expensive. Endovascular embolization can be selected for the treatment of cerebral aneurysms when economic conditions allow it.

5.
BMC Neurosci ; 23(1): 1, 2022 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-34979913

RESUMEN

OBJECTIVE: To analyse the risk factors for intracranial infection after neuroendoscopic transnasal pituitary adenoma resection (NTPAR) to provide a reference for the prevention and treatment of postoperative intracranial infection. METHODS: The clinical data of 387 patients who underwent NTPAR in the Department of Neurosurgery of the First People's Hospital of Yichang from March 2013 to March 2021 were retrospectively analysed. The patients were divided into an infected group and a noninfected group according to the occurrence of intracranial infection. The detailed clinical data of the two groups were collected. Univariate and multivariate logistic regression was used to analyse the risk factors for intracranial infection after NTPAR. RESULTS: Among the 387 surgical patients, 32 patients (8.27%) were in the intracranially infected group and 355 patients (91.73%) were in the noninfected group. The results of the univariate analysis suggested that age > 45 years, tumour size > 1 cm, operation time > 240 min, blood loss > 400 ml, Kelly Grade of cerebrospinal fluid (CSF) leakage > Grade 2, postoperative CSF leakage, lumbar cistern drainage and blood transfusion were the influencing factors for postoperative intracranial infection, while the results of multivariate logistic regression analysis implied that intraoperative CSF leakage (Kelly Grade > 2) and postoperative CSF leakage were independent influencing factors for intracranial infection after NTPAR, and perioperative use of antibiotics was an independent protective factor for postoperative intracranial infection. CONCLUSIONS: There are a variety of risk factors for intracranial infection after NTPAR, which indicates that it is necessary to develop different repair strategies for CSF leakage according to the Kelly Grade, timely treatment of postoperative CSF leakage and perioperative use of antibiotics. These measures have been shown to effectively reduce the probability of intracranial infection after NTPAR.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Adenoma/complicaciones , Adenoma/cirugía , Pérdida de Líquido Cefalorraquídeo/epidemiología , Pérdida de Líquido Cefalorraquídeo/etiología , Humanos , Persona de Mediana Edad , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/cirugía , Estudios Retrospectivos , Factores de Riesgo
6.
Anticancer Drugs ; 33(1): e434-e443, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34459459

RESUMEN

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used to treat non-small cell lung cancer. However, its off-targets are obscure, and systematic analysis of off-target activities remains to be performed. Here, we identified the off-targets of osimertinib using PharmMapper and DRAR-CPI and analyzed the intersected targets using the GeneMANIA and DAVID servers. A drug-target-pathway network was constructed to visualize the associations. The results showed that osimertinib is associated with 31 off-targets, 40 Kyoto Encyclopedia of Genes and Genomes pathways, and 9 diseases. Network analysis revealed that the targets were involved in cancer and other physiological processes. In addition to EGFR, molecular docking analysis showed that seven proteins, namely Janus kinase 3, peroxisome proliferator-activated receptor alpha, renin, mitogen-activated protein kinases, lymphocyte-specific protein tyrosine kinase, cell division protein kinase 2 and proto-oncogene tyrosine-protein kinase Src, could also be potential targets of osimertinib. In conclusion, osimertinib is predicted to target multiple proteins and pathways, resulting in the formation of an action network via which it exerts systematic pharmacological effects.


Asunto(s)
Acrilamidas/farmacología , Compuestos de Anilina/farmacología , Antineoplásicos/farmacología , Farmacología en Red/métodos , Proteínas/efectos de los fármacos , Simulación del Acoplamiento Molecular , Mapas de Interacción de Proteínas/fisiología
7.
BMC Neurol ; 21(1): 268, 2021 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-34229606

RESUMEN

BACKGROUND: Minimally invasive surgery has achieved good results in the treatment of cerebral haemorrhage.However, no large-scale clinical study has demonstrated that surgical treatment of cerebral haemorrhages less than 30 ml can improve the curative effect. Our study explored the efficacy and complication of stereotactic drainage based on the amount of cerebral hemorrhage (15-30 ml) in hypertensive basal ganglia. METHOD: Sixty patients with hypertensive basal ganglia haemorrhages were divided into a control group and an experimental group with 30 patients in each group. Patients in the control group were treated conservatively. In contrast, those in the experimental group received stereotactic drainage, and urokinase was injected into the haematoma cavity after the operation. The haematoma volume at admission and 1, 3, 7 and 30 days after treatment and National Institute of Health stroke scale(NIHSS) score data were recorded. Complications after treatment in the two groups of data were compared and analysed. RESULT: No significant differences in age, sex, time of treatment after onset, admission blood pressure, admission haematoma volume or admission NIHSS score were noted between these two groups (P > 0.05). After treatment, significant differences in haematoma volume were noted between the two groups on the 1st, 3rd, 7th and 30th days after treatment (P < 0.05). The amount of hematoma of patients in the experimental group was significantly reduced compared with that in the control group, and the NIHSS scores were significantly different on the 3rd, 7th and 30th days after treatment. The neurological deficit scores of patients in the experimental group were significantly reduced compared with those in the control group, and the incidence of pulmonary infection and venous thrombosis in the lower limbs of patients in the experimental group were significantly reduced (P < 0.05). ROC curve analysis showed that stereotactic drainage affected the early neurological function of patients with small and medium basal ganglia haemorrhages. CONCLUSION: For patients with small and medium basal ganglia haemorrhages, stereotactic drainage can be used due to the faster drainage speed of haematomas after operation, which is beneficial to the recovery of neurological function and reduce complications.


Asunto(s)
Hemorragia de los Ganglios Basales , Tratamiento Conservador , Drenaje , Técnicas Estereotáxicas , Hemorragia de los Ganglios Basales/diagnóstico por imagen , Hemorragia de los Ganglios Basales/terapia , Humanos , Hipertensión , Imagenología Tridimensional , Pronóstico , Curva ROC
8.
BMC Gastroenterol ; 20(1): 96, 2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32264830

RESUMEN

BACKGROUND: There are obviously ethnic differences between the UGT1A1 gene polymorphisms. Due to the difference of genetic background and environment, the treatment with colorectal cancer patients of Guangxi Zhuang should not completely follow the Euramerican or Chinese han patients. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. METHODS: From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 102 patients of this cohort with three generations of Zhuang, and 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled. The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1*28 and*6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method. RESULTS: UGT1A1*28 wild-type (TA6/6), heterozygous mutant (TA6/7) and homozygous mutant (TA7/7) accounted for 69.8, 30.2 and 0%, respectively. UGT1A1*6 wild type (G/G), heterozygous mutation type (G/A) and homozygous mutant (A/A) accounted for 76.7%, 20.9 and 2.3%, respectively. UGT1A1*28 TA6/7 type could increase the risk of grade 3~4 diarrhea (p = 0.027), which did not increase the risk of grade 3~4 neutropenia (p = 0.092). UGT1A1*6G/A and A/A type could increase the risk of grade 3~4 diarrhea and neutropenia (p = 0.001; p = 0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (p = 0.729; p = 0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1*28 and UGT1A1*6 (7.0 m vs 7.4 m, p = 0.427; 6.9 m vs 7.0 m p = 0.408). CONCLUSIONS: The distribution of UGT1A1*28 and UGT1A1*6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Glucuronosiltransferasa/genética , Irinotecán/uso terapéutico , Polimorfismo Genético , Adulto , Anciano , Antineoplásicos/efectos adversos , Camptotecina/uso terapéutico , China , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Genotipo , Humanos , Irinotecán/efectos adversos , Estimación de Kaplan-Meier , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia , Medicina de Precisión , Supervivencia sin Progresión , Estudios Retrospectivos , Resultado del Tratamiento
9.
Clin Exp Pharmacol Physiol ; 47(10): 1659-1663, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32469422

RESUMEN

PURPOSE: This retrospective study analyzed the polymorphisms and phenotypic frequencies of CYP2C9, CYP2C19 and CYP2D6 in a Han Chinese population. METHODS: Tests for polymorphisms of CYP2C9, CYP2C19 and CYP2D6 were performed in over 3000 (3099-3931) samples using an Illumina HiSeq X Ten sequencer. Following the guidance of the PharmGKB and PharmVar databases, the polymorphisms of CYP2C9, CYP2C19 and CYP2D6 were transformed into phenotypes, which included ultrarapid metabolizers (UMs), rapid metabolizers (RMs), normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). RESULTS: A total of 3122 samples were tested for polymorphisms in CYP2C9 and the overall polymorphism frequency was found to be 8.8%; the phenotypic frequency for CYP2C9 was 91.2% NMs, 8.23% IMs and 0.16%, PMs. The overall polymorphism frequency of CYP2C19 was tested in 3099 samples and found to be 60.1%; the phenotypic frequency for CYP2C19 was 39.9% NMs, with 1.06% RMs, 45.62% IMs and 13.42% PMs. The overall polymorphism frequency of CYP2D6 was tested in 3931 samples and found to be 88.04%; the phenotypic frequency of CYP2D6 was 95.43% NMs, 3.35% IMs and 0.52% PMs. Using 2690 samples, the polymorphisms and phenotypic distributions of CYP2C9, CYP2C19 and CYP2D6 were examined simultaneously. We found that 96.36% of the samples contained mutations while 66.51% corresponded with phenotypic changes. CONCLUSIONS: Polymorphisms and phenotypic changes of CYP2C9, CYP2C19 and CYP2D6 are relatively frequent in the Han Chinese population. Thus, preemptive pharmacogenetic testing of CYP2C9, CYP2C19 and CYP2D6 should be recommended prior to dosing substrate drugs.


Asunto(s)
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Fenotipo , China , Humanos
10.
Molecules ; 25(5)2020 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-32131410

RESUMEN

Peimine (also known as verticine) is the major bioactive and characterized compound of Fritillariae Thunbergii Bulbus, a traditional Chinese medicine that is most frequently used to relieve a cough. Nevertheless, its molecular targets and mechanisms of action for cough are still not clear. In the present study, potential targets of peimine for cough were identified using computational target fishing combined with manual database mining. In addition, protein-protein interaction (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using, GeneMANIA and Database for Annotation, Visualization and Integrated Discovery (DAVID) databases respectively. Finally, an interaction network of drug-targets-pathways was constructed using Cytoscape. The results identified 23 potential targets of peimine associated with cough, and suggested that MAPK1, AKT1 and PPKCB may be important targets of pemine for the treatment of cough. The functional annotations of protein targets were related to the regulation of immunological and neurological function through specific biological processes and related pathways. A visual representation of the multiple targets and pathways that form a network underlying the systematic actions of peimine was generated. In summary, peimine is predicted to exert its systemic pharmacological effects on cough by targeting a network composed of multiple proteins and pathways.


Asunto(s)
Cevanas/uso terapéutico , Biología Computacional , Tos , Perfilación de la Expresión Génica , Modelos Biológicos , Mapas de Interacción de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Cevanas/química , Tos/tratamiento farmacológico , Tos/genética , Tos/metabolismo , Medicamentos Herbarios Chinos , Humanos , Medicina Tradicional China
11.
J Cell Biochem ; 120(1): 658-670, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30203578

RESUMEN

Emerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole-genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non-cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region-5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection.


Asunto(s)
Neoplasias de la Mama/genética , Metilación de ADN/genética , Detección Precoz del Cáncer , Genoma Humano/genética , Proteínas de Homeodominio/genética , Factor I del Crecimiento Similar a la Insulina/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Factores de Transcripción/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , Metilación de ADN/efectos de los fármacos , Bases de Datos de Ácidos Nucleicos , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células MCF-7 , Persona de Mediana Edad , Ftalimidas/farmacología , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismo , Transcriptoma/genética , Triptófano/análogos & derivados , Triptófano/farmacología , Regulación hacia Arriba/genética
12.
Clin Exp Pharmacol Physiol ; 46(8): 689-693, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31009088

RESUMEN

Genetic polymorphisms impact biological responses to drugs. Current pharmacogenomics guidelines formulated by different countries, such as the Clinical Pharmacogenetics Implementation Consortium, the Dutch Pharmacogenetics Working Group, the Canadian Pharmacogenomics Network for Drug Safety, and the French National Network (Réseau) of Pharmacogenetics, play important roles in clinical practices. However, the standards for these guidelines vary significantly, resulting in differences in recommendations. The present article discusses these differences by head-to-head comparison of the existing pharmacogenomics guidelines and proposes new strategies for their future development.


Asunto(s)
Guías como Asunto , Farmacogenética/métodos , Humanos
13.
Int J Vitam Nutr Res ; 89(3-4): 168-175, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30806606

RESUMEN

Background: Vitamin E has anti-cancer properties, which was demonstrated mainly due to its antioxidant effect. Several epidemiological studies have investigated the association between vitamin E consumption and the risk of bladder cancer. However, the results were inconsistent. The meta-analysis study aimed to evaluate the association of vitamin E consumption and the risk of bladder cancer. METHODS: We conducted a systematic literature search in the electronic databases, which included MEDLINE, EMBASE and the Cochrane Library till 1 January 2016. The pooled relative risk ratios (RRs) with 95% confidence intervals (CIs) were calculated depending on the heterogeneity among studies. Subgroup analysis and sensitivity analysis were also performed. Publication bias was assessed using Begg's test and Egger's test. RESULTS: A total of 11 prospective studies (3 randomized clinical trials and 8 cohort studies) including 575601 participants were identified to be eligible for our present meta-analysis. The pooled RRs with 95% CI for highest versus lowest vitamin E consumption was 0.89 (0.78-1.00). An inverse linear association between vitamin E consumption and bladder cancer risk was detected in the dose response analysis. The results were also stable in the subgroup analysis and sensitivity analysis. Meanwhile, no obvious publication bias was observed. CONCLUSIONS: Our study indicates that vitamin E consumption was inversely associated with the risk of bladder cancer.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Vitamina E , Humanos , Oportunidad Relativa , Estudios Prospectivos
14.
BMC Cancer ; 18(1): 1141, 2018 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-30453909

RESUMEN

BACKGROUND: This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-ß-N-acetylglucosamine transferase (OGT) in human bladder cancer. METHODS: Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169). The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis. The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays. Cell apoptosis and cell cycle analysis were detected using flow cytometry. The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux. MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown. RESULTS: The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines. O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest. It also increased autophagy in bladder cancer cells. This study demonstrated increased autophagy pro-survival, but not pro-death. Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum. CONCLUSIONS: The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.


Asunto(s)
Apoptosis/fisiología , Proliferación Celular/fisiología , N-Acetilglucosaminiltransferasas/metabolismo , Neoplasias de la Vejiga Urinaria/enzimología , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Cisplatino/farmacología , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , N-Acetilglucosaminiltransferasas/genética , Procesamiento Proteico-Postraduccional , Interferencia de ARN , Tratamiento con ARN de Interferencia/métodos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
15.
Food Microbiol ; 76: 487-496, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30166178

RESUMEN

The objective of this study was to explore the core functional microbiota for the production of volatile flavour during the traditional brewing of Wuyi Hong Qu glutinous rice wine, one of the most typical representatives of rice wine in China. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that bacteria of Lactobacillus, Bacillus, Leuconostoc, Lactococcus, Raoultella, Staphylococcus, Pediococcus, and Weissella, and fungi of Saccharomyces, Saccharomycopsis, Rhizopus, Monascus, Pichia, Wickerhamomyces, Candida, and Aspergillus were the predominant genera during the traditional fermentation process. Principal component analysis (PCA) based on the relative abundance showed that both of bacterial and fungal communities varied significantly in different fermentation phases. Some predominant microbial species or genera (including bacteria of Bacillus spp., Staphylococcus spp., Weissella spp., and P. acidilactici, and fungi of M. purpureus, R. oryzae, R. arrhizus var. arrhizus, and A. niger) were detected at the initial brewing stage, and their populations decreased as the fermentation progressed, while those of Lactobacillus, Gluconacetobacter, Leuconostoc, Pichia, Wickerhamomyces, and Saccharomyces increased to become the predominant genera at the final stage. A total of 79 volatile compounds were identified in traditional fermentation starters and during the traditional brewing process, mainly including esters, alcohols, acids, aldehydes, ketones, and phenols. Heatmaps and PCA also revealed the significant variances in the composition of volatile compounds among different samples. Furthermore, the potential correlations between microbiota succession and volatile flavour dynamics were explored through bidirectional orthogonal partial least squares (O2PLS) based correlation analysis. Three bacterial genera, namely, Gluconacetobacter, Lactobacillus, Lactococcus, and three fungal genera of Pichia, Wickerhamomyces, and Saccharomyces, were determined as the core functional microbiota for production of main volatile compounds in Wuyi Hong Qu glutinous rice wine. To conclude, information provided by this study is valuable to the development of effective strategies for the selection of beneficial bacterial and fungal strains to improve the quality of Wuyi Hong Qu glutinous rice wine.


Asunto(s)
Bacterias/metabolismo , Aromatizantes/metabolismo , Hongos/metabolismo , Microbiota , Oryza/microbiología , Compuestos Orgánicos Volátiles/metabolismo , Vino/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Biodiversidad , China , Fermentación , Aromatizantes/química , Hongos/clasificación , Hongos/genética , Hongos/aislamiento & purificación , Oryza/química , Compuestos Orgánicos Volátiles/química , Vino/análisis
16.
Pak J Pharm Sci ; 31(2): 485-489, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29618439

RESUMEN

Taxanes, mainly group paclitaxel and docetaxel, are amongst the most promising anticancer agents that are widely used for a variety of tumor types. It is a great challenge to gain a quick overview of the molecular mechanisms of taxanes, owning to the massive amounts of data have been produced. Network pharmacology will be a powerful tool to uncover the drug-targets network of taxanes. In this study, drug-targets network of paclitaxel and docetaxel were constructed via STITCH by database mining, and its topological parameters and important nodes were analyzed. All will provide a systematic understanding for molecular mechanisms of pacltaxel and docetaxel in a quick and visual way.


Asunto(s)
Minería de Datos/métodos , Docetaxel/farmacología , Paclitaxel/farmacología , Subfamilia B de Transportador de Casetes de Unión a ATP , Antineoplásicos Fitogénicos/farmacología , Biología Computacional/métodos , Citocromo P-450 CYP2C8 , Bases de Datos Factuales , Receptores ErbB , Humanos , Terapia Molecular Dirigida/métodos , Mapeo de Interacción de Proteínas/métodos , Programas Informáticos , Taxoides/farmacología
17.
Acta Pharmacol Sin ; 38(4): 571-580, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28216622

RESUMEN

There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system. The short-term effects of primary tumor and lymph node after radiotherapy were assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) of WHO. And acute radiation-induced toxic reactions were evaluated according to the Radiation Therapy Oncology Group or European Organization for Research and Treatment of Cancer (RTOG/EORTC). The effects of gene polymorphisms on clinical outcomes of chemoradiotherapy were assessed by chi-square test, univariate and multivariate logistic regression analyses. We found that CT and CT+CC genotypes of CANX rs7566 was significantly correlated with primary tumor treatment efficacy at 3 months after chemoradiotherapy and with occurrence of radiation-induced myelosuppression in Chinese NPC patients. CT and CT+CC genotypes of CALCR rs2528521 were significantly correlated with cervical lymph node efficacy at 3 months after chemoradiotherapy. And CC and CT+CC genotypes of VCP rs2074549 were significantly associated with occurrence of myelosuppression. In conclusion, SNPs of VCP rs2074549, CANX rs7566 and CALCR rs2528521 in ER stress pathway genes may serve as predictors for clinical outcomes of chemoradiotherapy in Chinese NPC patients.


Asunto(s)
Carcinoma/terapia , Estrés del Retículo Endoplásmico/genética , Neoplasias Nasofaríngeas/terapia , Adenosina Trifosfatasas/genética , Adulto , Pueblo Asiatico , Calnexina/genética , Carcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Quimioradioterapia , Chaperón BiP del Retículo Endoplásmico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Polimorfismo Genético , Receptores de Calcitonina/genética , Transducción de Señal , Proteína que Contiene Valosina
18.
Clin Exp Pharmacol Physiol ; 44(5): 539-548, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28199751

RESUMEN

The purpose of this paper is to assess the relationship between gene polymorphism in angiogenesis-related genes and radiation responses in nasopharyngeal carcinoma (NPC) patients. The genotypes of 180 NPC patients were analyzed by Sequenom MassARRAY. The response evaluation criteria in solid tumours were used for assessing efficacies, and the criteria of the Radiation Therapy Oncology Group or European Organization for Research & Treatment of Cancer were utilized for evaluating acute toxic reactions in response to radiation. Statistical methods included chi-square test, uni- and multivariate logistic regression analyses. Genotypic carriers of rs1800541 GT were at an elevated risk of developing grade 3+ oral mucositis, and a genetic variant of rs5333 was a predictor for a lower occurring risk of grade 2+ radiation-induced xerostomia. EDN1 rs1800541, rs2071942 and rs5370 variants were associated with a significantly higher risk of severe myelosuppression. SNPs in such angiogenesis-related genes as EDN1 rs1800541, rs2071942 & rs5370 and EDNRA rs5333 may serve as useful biomarkers for predicting the outcomes of NPC patients.


Asunto(s)
Carcinoma/genética , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Neovascularización Patológica/genética , Neovascularización Patológica/radioterapia , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Endotelina-1/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Polimorfismo de Nucleótido Simple/efectos de la radiación , Resultado del Tratamiento , Adulto Joven
19.
BMC Womens Health ; 17(1): 14, 2017 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-28264686

RESUMEN

BACKGROUND: Breast cancer (breast Ca) is recognised as a major public health problem in the world. Data on reproductive factors associated with breast Ca in the Central African Republic (CAR) is very limited. This study aimed to identify reproductive variables as risk factors for breast Ca in CAR women. METHODS: A case-control study was conducted among 174 cases of breast Ca confirmed at the Pathology Unit of the National Laboratory in Bangui between 2003 and 2015 and 348 age-matched controls. Data collection tools included a questionnaire, interviews and a review of medical records of patients. Data were analysed using SPSS software version 20. Odd ratios and 95% confidence intervals (CI) for the likelihood of developing breast Ca were obtained using unconditional logistic regression. RESULTS: In total, 522 women with a mean age of 45.8 (SD = 13.4) years were enrolled. Women with breast Ca were more likely to have attained little or no education (AOR = 11.23, CI: 4.65-27.14 and AOR = 2.40, CI: 1.15-4.99), to be married (AOR = 2.09, CI: 1.18-3.71), to have had an abortion (AOR = 5.41, CI: 3.47-8.44), and to be nulliparous (AOR = 1.98, CI: 1.12-3.49). Decreased odds of breast Ca were associated with being employed (AOR = 0.32, CI: 0.19-0.56), living in urban areas (AOR = 0.16, CI: 0.07-0.37), late menarche (AOR = 0.18, CI: 0.07-0.44), regular menstrual cycles (AOR = 0.44, CI: 0.23-0.81), term pregnancy (AOR = 0.26, CI: 0.13-0.50) and hormonal contraceptive use (AOR = 0.62, CI: 0.41-0.93). CONCLUSION: Breast Ca risk factors in CAR did not appear to be significantly different from that observed in other populations. This study highlighted the risk factors of breast Ca in women living in Bangui to inform appropriate control measures.


Asunto(s)
Neoplasias de la Mama/epidemiología , Reproducción , Medición de Riesgo , Aborto Inducido/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/etiología , Estudios de Casos y Controles , República Centroafricana/epidemiología , Distribución de Chi-Cuadrado , Escolaridad , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Ocupaciones/estadística & datos numéricos , Oportunidad Relativa , Paridad , Embarazo , Sistema de Registros , Encuestas y Cuestionarios
20.
BMC Urol ; 17(1): 38, 2017 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-28558682

RESUMEN

BACKGROUND: Renal cell carcinoma (RCC) is one of the most common types of cancer in urological system worldwide. Recently, the anticancer role of Glucosamine has been studied in many types of cancer. The aim of this study was to investigate the effects of Glucosamine on RCC. METHODS: The effects of Glucosamine on RCC cell proliferation and apoptosis were investigated by MTT assay and Annexin V-FITC Apoptosis assay, respectively in vitro. Cell cycle was detected by flow cytometry after treatment with Glucosamine. Protein levels of several cell cycle associated markers were examined by Western Blot. RESULTS: Our data showed that Glucosamine significantly inhibited the proliferation of renal cancer 786-O and Caki-1 cells in a dose-dependent manner. Besides, Glucosamine treatment resulted in cell cycle arrest at G0/G1 phase in both cell lines. Meanwhile, the expression of several regulators that contribute to G1/S phased transition, such as Cyclin D1, CDK4 and CDK6, were significantly down-regulated with the up-regulation of cell cycle inhibitors, p21 and p53, after treatment with glucosamine. However, the apoptosis rate of RCC cells was down-regulated when treatment with Glucosamine at 1 mM and 5 mM, while up-regulated at 10 mM. CONCLUSIONS: Our findings indicated that Glucosamine inhibited the proliferation of RCC cells by promoting cell cycle arrest at G0/G1 phase, but not promoting apoptosis. The present results suggested that Glucosamine might be a potential therapeutic agent in RCC treatment in the future.


Asunto(s)
Carcinoma de Células Renales/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Glucosamina/farmacología , Neoplasias Renales/patología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fase G1/efectos de los fármacos , Humanos , Células Tumorales Cultivadas
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