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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1033-1039, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418353

RESUMO

]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL). METHODS: The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups. RESULTS: There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P>0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037,0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770). CONCLUSION: For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.


Assuntos
Leucemia Promielocítica Aguda , Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Tretinoína
2.
Chin J Nat Med ; 17(5): 355-362, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31171270

RESUMO

Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1ß, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·L-1vs (5626.4 ± 795.1)U·L-1], DAO [(1100.1 ± 334.3) U·L-1vs (1666.4 ± 525.3) U·L-1] and CRP [(7.6 ± 1.2) µg·mL-1vs (17.8 ± 3.8) µg·mL-1]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mL-1vs (90.1 ± 14.9) pg·mL-1] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.

4.
Forensic Sci Int Genet ; 41: 145-151, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31103798

RESUMO

In forensics, ancestry inference can provide leads for criminal investigation. Therefore, the time needed to generate results is the first priority. Single nucleotide polymorphisms (SNPs) are widely used genetic markers for ancestry inference. In this study, a rapid microfluidic-based SNP genotyping (MSG) chip was established to detect 72 autosomal SNPs for ancestry inference of East Asian populations. The DNA template was infused into the chip and distributed into reaction chambers with pre-spotted primer pairs under centrifugation. After sealing the inlets/outlets and the connections among adjacent reaction chambers, the chip was placed onto a plate thermocycler for competitive allele-specific PCR. The SNP genotyping results were generated by analyzing the extracted fluorescence signal of each reaction chamber after PCR was completed. The detection process took less time (2.5 h) and was simpler than other SNP genotyping methods, such as SNaPshot and MassArray. To assess the performance of the chip, its accuracy, specificity, and sensitivity were evaluated. A total of 50 samples were genotyped using the chip, and the consistency of all of the typing and sequencing results was 100%. For ancestry inference of unknown individuals, a reference database of 3628 individuals from 57 populations was employed, and the ancestry origin of 110 test samples was inferred, demonstrating that the differentiation of East Asian subpopulations can be achieved through the MSG chip method. Overall, the MSG chip method established in this study can effectively be used for rapid and accurate ancestry inference.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Genótipo , Dispositivos Lab-On-A-Chip , Polimorfismo de Nucleotídeo Único , China , Genética Populacional , Humanos , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade
5.
Lancet Oncol ; 20(4): 591-600, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30880070

RESUMO

BACKGROUND: Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. METHODS: In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. FINDINGS: Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660-0·826] in region 1, 0·734 [0·651-0·814] in region 2, and 0·736 [0·649-0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81-10·07] in the internal testing set, 5·39 [3·38-8·59] in the independent validation set, and 4·62 [2·48-8·61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0·811 [95% CI 0·756-0·861]). INTERPRETATION: Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

6.
Chem Biol Interact ; 300: 18-26, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30611790

RESUMO

Chronic pancreatitis is characterized by pancreatic fibrosis, associated with excessive activation of pancreatic stellate cells (PSCs) and increased expression of transforming growth factor-ß1 (TGF-ß1). Recently, our studies have shown that autophagy inhibitor could inhibit PSCs activation and reduce collagen secretion. Saikosaponin d (SSd), the major active component of bupleurum falcatum (a medicinal plant), has anti-fibrosis effects in liver. However, it is unclear whether SSd has a role in pancreatic fibrosis. This study aimed to investigate the effect of SSd on the autophagy and activation of PSCs in vivo and in vitro. In vivo, a rat chronic pancreatitis model was induced by intravenous injection of dibutyltin dichloride. SSd was administered at a dose of 2.0 mg/kg body weight per day by gavage. After 4 weeks, the pancreas was collected for histological and molecular analysis. In vitro, PSCs were isolated and cultured for treatment with different dosages of SSd. The results showed that SSd inhibited PSCs autophagy and activation while also reducing extracellular matrix (ECM) formation and pancreatic damage. SSd inhibited autophagy through activating the PI3K/Akt/mTOR pathway. SSd also promoted degradation of ECM with an increasing ratio of MMPs/TIMPs and suppressed the TGF-ß1/Smads pathway. From these results, we concluded that SSd prevents pancreatic fibrosis by reducing autophagy of PSCs through PI3K/Akt/mTOR pathway, which has crosstalk with the TGF-ß1/Smads pathway.


Assuntos
Autofagia/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Pâncreas/efeitos dos fármacos , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Células Cultivadas , Matriz Extracelular/metabolismo , Fibrose , Masculino , Metaloproteinases da Matriz/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Compostos Orgânicos de Estanho/toxicidade , Pâncreas/metabolismo , Pâncreas/patologia , Células Estreladas do Pâncreas/citologia , Células Estreladas do Pâncreas/efeitos dos fármacos , Células Estreladas do Pâncreas/metabolismo , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/patologia , Pancreatite Crônica/prevenção & controle , Pancreatite Crônica/veterinária , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Saponinas/uso terapêutico , Proteínas Smad/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
7.
Yi Chuan ; 40(11): 1024-1032, 2018 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-30465535

RESUMO

The ectodysplasinA receptor gene (EDAR) plays an important role in the development of ectoderm. The derived G allele of its key missense variant EDARV370A is prevalent in East Asians and Americans, but rare in Africans and Europeans. This leads to distinct ectodermal-derived phenotypes between different continental groups, such as the straighter and thicker hair, more eccrine sweat glands, feminine smaller breasts, shovel incisors characteristic of East Asians. At present, we know little about the association between EDARV370A and facial and ear morphology characteristics. To better understand the effect of EDARV370A on craniofacial phenotypes, we systematically examined the association between EDARV370A and 136 facial quantitative phenotypes, one chin ordinal phenotype and six ear ordinal phenotypes in 715 Uyghurs. The quantitative phenotypes were derived by applying our automated landmark annotation method to facial 3D photos and the ordinal phenotypes were manually graded from facial 2D photos. The analysis identified significant association (P<0.05 after multiple testing correction) between EDARV370A and eight facial phenotypes, one chin phenotype and three ear morphology phenotypes. Our study thus elucidated the pleotropic effect of EDARV370A on craniofacial phenotypes in a European-Asian admixed Uyghur population.

8.
Microb Ecol ; 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30357425

RESUMO

Titanium ions significantly promote plant growth, but the mechanism is still unclear. Cut flowers are ideal materials for the study of plant growth and senescence. In this study, freshly cut Gerbera jamesonii were used to study the effects of titanium ions (8 mg/L) on the flower longevity. Flowering observation showed that the gerbera vase life was significantly prolonged in the presence of titanium ions. Plate colony counts showed that the amounts of bacteria in the vase solution of the control group were approximately 1700 times more than that of titanium ion treatment group. High-throughput sequencing was used to determine the sequences of 16S rRNA gene V3-V4 variable regions of the vase solutions to analyze bacterial species, their average proportions, and absolute abundance. The results showed that the titanium ions reduced the entire bacterial counts as well as altered the absolute abundance of different bacterial species in the vase solution. The most prevalent bacteria were mainly Enterobacteriaceae, Pseudomonas veronii, Pseudomonas sp., Delftia sp., Agrobacterium sp., Sphingobacterium multivorum, Acinetobacter johnsonii, and Clostridiaceae. In combination with plate colony counts, we demonstrated that all the bacterial growths were significantly inhibited by titanium ions, regardless of their average proportions increased or decreased. These results showed that titanium ions could extend effectively the longevity of gerberas and possess the broad-spectrum antibacterial properties. This study provides a basis for further mechanism exploration of titanium ions action and its applications in cut flower preservation and agricultural production.

9.
Int J Mol Med ; 42(5): 2750-2762, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226562

RESUMO

GPR17 is a G (i)-coupled dual receptor, linked to P2Y and CysLT receptors stimulated by uracil nucleotides and cysteinyl leukotrienes, respectively. Recent evidence has demonstrated that GPR17 inhibition ameliorates the progression of cerebral ischemic injury by regulating neuronal death and microglial activation. The present study aimed to assess the detailed regulatory roles of this receptor in oxygen­glucose deprivation/recovery (OGD/R)­induced ischemia­like injury in vitro and explore the underlying mechanism. The results demonstrated that OGD/R induced ischemic neuronal injury and microglial activation, including enhanced phagocytosis and increased inflammatory cytokine release in neuron­glial mixed cultures of cortical cells. GPR17 upregulation during OGD/R was spatially and temporally correlated with neuronal injury and microglial activation. In addition, GPR17 knockdown inhibited OGD/R­induced responses in neuron­glial mixed cultures. GPR17 knockdown also attenuated cell injury induced by the agonist leukotriene D4 (LTD4) or uridine 5'­diphosphate (UDP) in neuron­glial mixed cultures. However, GPR17 knockdown did not affect OGD/R­induced ischemic neuronal injury in primary cultures of neurons. In primary astrocyte cultures, neither GPR17 nor OGD/R induced injury. By contrast, GPR17 knockdown ameliorated OGD/R­induced microglial activation, boosting phagocytosis and inflammatory cytokine release in primary microglia cultures. Finally, the results demonstrated that the conditioned medium of microglia pretreated with OGD/R induced neuronal death, and the neuronal injury was significantly inhibited by GPR17 knockdown. These findings suggested that GPR17 may mediate ischemia­like neuronal injury and microglial activation in vitro; however, the protective effects on ischemic neuronal injury might depend upon microglial activation. Whether GPR17 regulates neuronal injury mediated by oligodendrocyte linkage remains to be investigated.

10.
Gene ; 675: 301-311, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30180969

RESUMO

OBJECTIVE: The inhibition of Aluminum (Al)-induced root tip cell elongation is a major cause of plant root elongation suppression. The inhibition of root tip cell elongation is caused by a disruption of cell wall component metabolism, growth signaling, or cellular damage. The aim of this study was to identify the proteins involved in the metabolism of the root cell wall components under Al stress in the Al-tolerant wheat (Triticum aestivum L.) cultivar ET8. METHODS: Differentially expressed proteins of Al-tolerant wheat roots were screened via isobaric tags for relative and absolute quantification (iTRAQ). Furthermore, their expression changes were detected via RT-PCR analysis. The contents of major components of the cell wall and their changes in metabolic enzyme activities were also investigated. RESULTS: A total of 97 differentially expressed proteins from Al-tolerant wheat roots were screened and nine of these 97 proteins were root cell wall component related. The known nucleic acid sequences of proteins were 14-3-3 protein, the plasm membrane (PM) H+-ATPase, phospholipase D, peroxidase, and glycosyltransferase. For 14-3-3 protein, phospholipase D and peroxidase, the protein expression and mRNA expression were consistent with Al-treatment; however, for PM H+-ATPase and glycosyltransferase, the protein expression and mRNA expression were inconsistent under Al-stress. Furthermore, both cellulase activity and callase activity were down-regulated by Al stress, while the phenylalanineammonialyase (PAL), cinnamyl alcohol dehydrogenase (CAD), and peroxidase (POD) activities were up-regulated. Furthermore, the PM H+-ATPase activity was decreased in response to Al stress. In addition, the contents of callose, cellulose, lignin, and H2O2 varied significantly. CONCLUSIONS: The cell wall components, relative metabolism enzymes activity, and gene expression also changed followed by protein expression changed in response to Al stress. The results suggest that Al stress leads to marked variations in metabolic enzyme activity, carbohydrate content, followed by changes of root cell components in wheat roots.


Assuntos
Alumínio/toxicidade , Proteínas de Plantas/metabolismo , Raízes de Plantas/citologia , Triticum/efeitos dos fármacos , Triticum/metabolismo , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Enzimas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Proteômica/métodos , Estresse Fisiológico/efeitos dos fármacos , Triticum/citologia
11.
Cancer Biother Radiopharm ; 33(6): 241-251, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30048163

RESUMO

BACKGROUND: The long noncoding RNA HOTAIR (HOX transcript antisense intergenic RNA) has been reported to be a biomarker for various malignant tumors; however, its involvement in breast cancer is not fully understood. The aim of this study was to investigate the effects involved with long noncoding RNA HOTAIR and EZH2 (enhancer of zeste homologue 2) on the processes of proliferation, invasion, migration, and apoptosis of breast cancer cells. MATERIALS AND METHODS: The expressions of HOTAIR and EZH2 in both normal human mammary epithelial cell (HBL-100) and breast cancer cell lines (MCF-7, MDA-MB-231, and SKBR-3) were detected by means of reverse transcription-quantitative polymerase chain reaction. The MCF-7 cells that exhibited the highest HOTAIR expressions were selected for further studies and divided into the control, negative control, and small interfering RNA-HOTAIR groups. The proliferation, invasion, migration, and apoptosis of breast cancer cells were evaluated by MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. The combination of HOTAIR with EZH2 and PTEN was predicted by bioinformation, with a dual-luciferase reporter gene assay providing further verification. RESULTS: Initially, lower expressions of HOTAIR and EZH2 in the normal human mammary epithelial cells, while higher expressions in the breast cancer cells of MCF-7, MDA-MB-231, and SKBR-3 were detected. In addition, the downregulation of HOTAIR or silencing of EZH2 was revealed to repress the proliferation, invasion, and migration, while acting to promote the apoptosis of the breast cancer cells. Furthermore, HOTAIR could bind specifically to EZH2 and PTEN, highlighting the capability of HOTAIR to inhibit the expression of PTEN by recruiting EZH2 in breast cancer, while the TCGA database demonstrated the expressions of PTEN were lower in breast cancer cells. CONCLUSIONS: The study suggests the higher expressions of HOTAIR and EZH2 among three breast cancer cells. Furthermore, the downregulation of HOTAIR or silencing of EZH2 was noted to inhibit the proliferation, invasion, and migration of breast cancer cells, while promoting their apoptosis.

12.
Life Sci ; 208: 276-283, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30056017

RESUMO

AIMS: Autophagy is an intracellular metabolic process that degrades and recycles own constituents to maintain homeostasis and supply substrates. Disruption of collagen degradation is one of the pathogenesis of pancreatic fibrosis. In this study, we investigated the effects of inhibiting autophagy on the collagen degradation of PSCs. MAIN METHODS: Rats were injected dibutyltin dichloride (DBTC) to induce chronic pancreatitis (CP) model. The expression of LC3B was measured by western blotting. Rat PSCs were isolated from pancreas tissues, and the experiments used the primary PSCs. Autophagosome was confirmed by transmission electron microscope. Immunofluorescence for LC3B and α-SMA were applied to assess autophagy and activated PSCs. The effects of autophagy inhibition of 3-MA on the expressions of LC3B, Atg5, and Beclin-1 were investigated by real-time PCR and Western blotting, as well as the α-SMA, TGF-ß1, ColI, Col III, FN, MMP-2, MMP-13, TIMP-1 and TIMP-2. Meanwhile, the secretion of ColI, Col III and FN were investigated by ELISA. KEY FINDINGS: The LC3-II/I ratio was increased in rat CP model. Autophagosomes and an increased autophagic level were observed during PSCs activation. Inhibiting autophagy could down-regulate the expressions of α-SMA, TGF-ß1, FN, ColI, Col III, TIMP-1 and TIMP-2, while the expressions of MMP-2 and MMP-13 were increased. SIGNIFICANCE: This study confirmed that autophagic level is increased during PSCs activation in vivo and in vitro. Inhibiting autophagy prevents the activation of PSCs, and suppresses fibrosis through promoting extracellular matrix (ECM) degradation by decreasing the expression of TGF-ß1 and increasing MMPs/TIMPs ratio.


Assuntos
Autofagia , Colágeno Tipo III/metabolismo , Matriz Extracelular/metabolismo , Metaloproteinases da Matriz/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/patologia , Animais , Células Cultivadas , Colágeno Tipo III/genética , Masculino , Metaloproteinases da Matriz/genética , Proteínas Associadas aos Microtúbulos/genética , Compostos Orgânicos de Estanho/toxicidade , Células Estreladas do Pâncreas/metabolismo , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/metabolismo , Proteólise , Ratos , Ratos Wistar , Teratogênios/toxicidade , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
13.
Int J Legal Med ; 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29882060

RESUMO

Inferring an unknown DNA's ancestry using a set of ancestry-informative single nucleotide polymorphisms (SNPs) in forensic science is useful to provide investigative leads. This is especially true when there is no DNA database match or specified suspect. Thus, a set of SNPs with highly robust and balanced differential power is strongly demanded in forensic science. In addition, it is also necessary to build a genotyping database for estimating the ancestry of an individual or an unknown DNA. For the differentiation of Africans, Europeans, East Asians, Native Americans, and Oceanians, the Global Nano set that includes just 31 SNPs was developed by de la Puente et al. Its ability for differentiation and balance was evaluated using the genotype data of the 1000 Genomes Phase III project and the Stanford University HGDP-CEPH. Just 402 samples were genotyped and analyzed as a reference set based on statistical methods. To validate the differentiating capacity using more samples, we developed a single-tube 28-plex SNP assay in which the SNPs were chosen from the 31 allelic loci of the Global AIMs Nano set. Three tri-allelic SNPs used to differentiate mixed-source DNA contribute little to population differentiation and were excluded here. Then, 998 individuals from 21 populations were typed, and these genotypes were combined with the genotype data obtained from 1000 Genomes Phase III and the Stanford University HGDP-CEPH (3090 total samples,43 populations) to estimate the power of this multiplex assay and build a database for the further inference of an individual or an unknown DNA sample in forensic practice.

14.
Forensic Sci Int Genet ; 35: e10-e12, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29803513

RESUMO

Over the last decade, several panels of ancestry-informative markers have been proposed for the analysis of population genetic structure. The differentiation efficiency depends on the discriminatory ability of the included markers and the reference population coverage. We previously developed a small set of 27 autosomal single nucleotide polymorphisms (SNPs) for analyzing African, European, and East Asian ancestries. In the current study, we gathered a high-coverage reference database of 110 populations (10,350 individuals) from across the globe. The discrimination power of the panel was re-evaluated using four continental ancestry groups (as well as Indigenous Americans). We observed that all the 27 SNPs demonstrated stratified population specificity leading to a striking ancestral discrimination. Five markers (rs728404, rs7170869, rs2470102, rs1448485, and rs4789193) showed differences (δ > 0.3) in the frequency profiles between East Asian and Indigenous American populations. Ancestry components of all involved populations were accurately accessed compared with those from previous genome-wide analyses, thereafter achieved broadly population separation. Thus, our ancestral inference panel of a small number of highly informative SNPs in combination with a large-scale reference database provides a high-resolution in estimating ancestry compositions and distinguishing individual origins. We propose extensive usage in biomedical studies and forensics.

15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 116-120, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397828

RESUMO

OBJECTIVE: To investigate the correlation of the serum minimal concentrations (Cmins) of nilotinib(NIL) with the clinical efficacy and adverse events (AEs) in CML patients. METHODS: A total of 54 patients were divided into two groups according to the dosage of nilotinib. 44 cases received dose of 600-800 mg/d were classified as group A; while 10 cases received dose of 400 mg/d as group B. The Cmins of nilotinib were determmined by liquid chromatography-tandem mass spectrometry. RESULTS: Median Cmins of nilotinib in 54 patients was 1.71 (0.52-5.93) µg/ml. Cmins of nilotinib in group A and group B were 2.09± 1.21 µg/ml and 0.94± 0.27 µg/ml respectively, Cmins of group A was significantly higher than that of group B (P=0.001). In group A, 24 out of 44 cases obtained major molecular response (MMR) in 12 months, while 20 cases did not reach MMR in 12 months; the serum drug concentrations were 1.70± 0.75 µg/ml and 2.03± 0.82 µg/ml respectively, without statistically significant differences between these 2 subgroups(P=0.154). However, Cmins of nilotinib in patients with III-IV grade of adverse events were significantly higher than those in patients with 0-II grade of adverse events (3.09± 1.76 µg/ml vs 1.76± 0.68 µg/ml)(P=0.018). There was no statistic diffence in Cmins of nilotinib with MMR in 12 months of group A MMR 1.15± 0.27 µg/ml vs no MMR 0.83± 0.24 µg/ml(P=0.051). The MMR rate at 12 months in group A was 54.5%(24/44) and that in group B was 40%(4/10) (P=0.494). But the incidence of grade III-IV adverse events in group A was 29.5%(13/44), which was significantly higher than that of group B[0/10(0%)]. CONCLUSION: Cmins of nilotinib shows significant individual differences. The Cmins of nilotinib relate with the dosage and grade III-IV of adverse events. The lower dose of nilotinib may maintain a good therapeutic effect and significantly reduce the adverse events.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos , Humanos , Mesilato de Imatinib , Pirimidinas , Resultado do Tratamento
16.
Chin J Integr Med ; 24(4): 272-277, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28497397

RESUMO

OBJECTIVE: To investigate the effect of combined application of Xuebijing Injection ( , XBJ) and resolvin D1 (RvD1) on survival rate and the underlying mechanisms in mice with sepsisinduced lung injury. METHODS: The cecal ligation and puncture (CLP) method was used to develop a mouse sepsis model. Specific pathogen free male C57BL/6 mice were randomly divided into 5 groups (n=20 each): sham, CLP, CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1. After surgery, mice in the CLP+XBJ, CLP+RvD1 and CLP+XBJ+RvD1 groups were given XBJ (25 µL/g body weight), RvD1 (10 ng/g body weight), and their combination (the same dose of XBJ and RvD1), respectively. In each group, 12 mice were used to observe 1-week survival rate, while the rest were executed at 12 h. Whole blood was collected for flow cytometric analysis of leukocyte adhesion molecules CD18, lung tissues were harvested for observing pathological changes, and testing the activity of myeloperoxidase (MPO) and the expression of intercellular cell adhesion molecule 1 (ICAM-1). RESULTS: Compared with the CLP group, the histopathological damage of the lung tissues was mitigated, MPO activity was decreased in the CLP+XBJ and CLP+RvD1 groups (P<0.05). In addition, the 1-week survival rate was improved, proportion of CD18-expressing cells in whole blood and ICAM-1 protein expression in lung tissue were decreased in the CLP+XBJ+RvD1 group (P<0.05 or P<0.01). CONCLUSIONS: XBJ together with RvD1 could effectively inhibit leukocyte adhesion, reduce lung injury, and improve the survival rate of mice with sepsis.


Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Leucócitos/patologia , Lesão Pulmonar/complicações , Lesão Pulmonar/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Animais , Antígenos CD18/metabolismo , Adesão Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Injeções , Molécula 1 de Adesão Intercelular/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/patologia , Lesão Pulmonar/sangue , Masculino , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Sepse/sangue , Análise de Sobrevida
17.
Oncotarget ; 8(43): 74178-74187, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088777

RESUMO

Esophageal carcinoma (EC) is a malignancy with high metastatic potential. Chromosomal helicase/ATPase DNA binding protein 1-like (CHD1L) gene is a newly identified oncogene located at Chr1q21, and it is amplified in many solid tumors. However, the status of CHD1L protein expression in EC and its clinical significance is uncertain. This study was designed to investigate the significance of CHD1L expression in human EC and its biological function in EC cells. The expression of CHD1L was examined by immunohistochemistry in 191 surgically resected ECs. The associations between CHD1L expression and clinical pathological parameters and the prognostic value of CHD1L were analyzed. Western blot analysis showed that CHD1L was overexpressed in EC cell lines. In addition, positive CHD1L expression was strongly related to advanced clinical stage (P<0.01), and lymph node metastasis (P<0.01) of EC. The Kaplan-Meier curve indicated that high expression of CHD1L may result in poor prognosis of EC patients (P<0.01), and multivariate analysis showed that CHD1L overexpression was an independent predictor of overall survival. Furthermore, suppression of CHD1L in EC cells increased apoptosis and decreased cell proliferation invasion ability. Our results suggest that CHD1L is a target oncogene with the potential to serve as a novel prognostic biomarker in EC pathogenesis.

18.
J Zhejiang Univ Sci B ; 18(7): 597-604, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28681584

RESUMO

Marsdeniae tenacissimae extract (MTE) has been used as an adjuvant medicine for cancer therapy for a long time. Although massive studies demonstrated its considerable anti-cancer effect, there is no research on its influence on erythrocytes, which are firstly interacted with MTE in the circulation. To investigate the influence of MTE on erythrocytes, we used a flow cytometer to detect the MTE-treated alternations of morphology, calcium concentration, and reactive oxygen species (ROS) level in erythrocytes. We used hemolysis under different osmotic solutions to evaluate the fragility of erythrocytes. Data showed that MTE treatment dose-dependently increased the ratio of erythrocyte fragmentation (P<0.001) and shrinking, and elevated the forward scatter (FSC) value (P<0.001) and calcium accumulation (P<0.001). MTE induced ROS production of erythrocytes under the high glucose condition (P<0.01) and consequently caused a rise in fragility (P<0.05). These results suggest that MTE induces cytotoxicity and aging in erythrocytes in a dose-dependent manner, and presents the possibility of impairment on cancer patients' circulating erythrocytes when MTE is used as an anti-cancer adjuvant medicine.


Assuntos
Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Eritrócitos/efeitos dos fármacos , Marsdenia/química , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Senescência Celular , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Eritrócitos/citologia , Citometria de Fluxo , Glucose/análise , Hemólise , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Espalhamento de Radiação
19.
Nat Commun ; 8: 15337, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28643803

RESUMO

The von Hippel-Lindau (VHL) is deficient in ∼70% of clear-cell renal cell carcinomas (ccRCC), which contributes to the carcinogenesis and drug resistance of ccRCC. Here we show that VHL-deficient ccRCC cells present enhanced cytotoxicity of anthracyclines in a hypoxia-inducible factor-independent manner. By subtractive proteomic analysis coupling with RNAi or overexpression verification, aldehyde dehydrogenase 2 (ALDH2) is found to be transcriptionally regulated by VHL and contributes to enhanced anthracyclines cytotoxicity in ccRCC cells. Furthermore, VHL regulates ALDH2 expression by directly binding the promoter of -130 bp to -160 bp to activate the transcription of hepatocyte nuclear factor 4 alpha (HNF-4α). In addition, a positive correlation is found among the protein expressions of VHL, HNF-4α and ALDH2 in ccRCC samples. These findings will deepen our understanding of VHL function and shed light on precise treatment for ccRCC patients.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Antraciclinas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Regulação para Baixo/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Animais , Antraciclinas/farmacologia , Antraciclinas/toxicidade , Carcinoma de Células Renais/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fator 4 Nuclear de Hepatócito/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/patologia , Masculino , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Proteômica , Transcrição Genética/efeitos dos fármacos
20.
Analyst ; 142(11): 2004-2012, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28513665

RESUMO

We have successfully developed an integrated microsystem that combines two plastic microchips for DNA extraction and PCR amplification with a glass capillary array electrophoresis chip together in a compact control and detection instrument for automated forensic short tandem repeat (STR) analysis. DNA extraction followed by an "in situ PCR" was conducted in a single reaction chamber of the microchip based on a filter paper-based extraction methodology. PCR products were then mixed with sizing standards by an injection electrode and injected into the electrophoresis chip for four-color confocal fluorescence detection. The entire STR analysis can be completed in about two hours without any human intervention. Since the 15-plex STR system has a more stringent requirement for PCR efficiency, we optimized the structure of the plastic DNA extraction and amplification chip, in which the reaction chamber was formed by sandwiching a hollow structure layer with two blank cover layers, to reduce the adsorption of PCR reagents to the surfaces. In addition, PCR additives, bovine serum albumin, poly(ethylene glycol), and more magnesium chloride were included into the on-chip multiplex STR system. The limit-of-detection study demonstrated that our microsystem was able to produce full 15-plex STR profiles from 3.75 ng standard K562 DNA. Buccal swab and whole blood samples were also successfully typed by our system, validating the feasibility of performing rapid DNA typing in a "sample-in-answer-out" manner for on-site forensic human identification.

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