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1.
J Proteome Res ; 23(5): 1713-1724, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38648079

RESUMO

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.


Assuntos
Autofagia , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Progressão da Doença , Neoplasias Pulmonares , Ornitina Descarboxilase , Feminino , Humanos , Masculino , Células A549 , Autofagia/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Ornitina Descarboxilase/metabolismo , Ornitina Descarboxilase/genética , Prognóstico , Regulação para Cima
2.
Eur J Pediatr ; 183(3): 1381-1388, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38165463

RESUMO

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.


Assuntos
Substância Branca , Criança , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética , Atrofia Muscular
3.
J Integr Plant Biol ; 65(4): 934-949, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36515424

RESUMO

Cell wall is the first physical barrier to aluminum (Al) toxicity. Modification of cell wall properties to change its binding capacity to Al is one of the major strategies for plant Al resistance; nevertheless, how it is regulated in rice remains largely unknown. In this study, we show that exogenous application of putrescines (Put) could significantly restore the Al resistance of art1, a rice mutant lacking the central regulator Al RESISTANCE TRANSCRIPTION FACTOR 1 (ART1), and reduce its Al accumulation particularly in the cell wall of root tips. Based on RNA-sequencing, yeast-one-hybrid and electrophoresis mobility shift assays, we identified an R2R3 MYB transcription factor OsMYB30 as the novel target in both ART1-dependent and Put-promoted Al resistance. Furthermore, transient dual-luciferase assay showed that ART1 directly inhibited the expression of OsMYB30, and in turn repressed Os4CL5-dependent 4-coumaric acid accumulation, hence reducing the Al-binding capacity of cell wall and enhancing Al resistance. Additionally, Put repressed OsMYB30 expression by eliminating Al-induced H2 O2 accumulation, while exogenous H2 O2 promoted OsMYB30 expression. We concluded that ART1 confers Put-promoted Al resistance via repression of OsMYB30-regulated modification of cell wall properties in rice.


Assuntos
Oryza , Oryza/genética , Oryza/metabolismo , Alumínio/toxicidade , Putrescina/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Parede Celular/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Raízes de Plantas/metabolismo
4.
J Neuroradiol ; 50(2): 253-257, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36609069

RESUMO

BACKGROUND AND PURPOSE: Knowledge of nerve fascicular structures is essential for managing peripheral nerve disorders. This study aimed to investigate the feasibility of z-axis high-resolution magnetic resonance (MR) microneurography (zH-MRMN) in displaying the three-dimensional structures of tibial nerve fascicles in vivo using a 3T MR scanner. MATERIALS AND METHODS: Twelve volunteers underwent z-axis conventional-resolution MR microneurography (zC-MRMN) and zH-MRMN of tibial nerves. The visibility scores of the nerve fascicles (VSNFs) on axial zC-MRMN images and axial zH-MRMN multiplanar reformation (MPR) images were compared. The nerve fascicle appearances on the longitudinal zH-MRMN MPR images were described. RESULTS: In the nerve segments whose long axes were perpendicular to the imaging planes of both zC-MRMN and zH-MRMN, the VSNFs were not significantly different between the axial images of the two modalities (P = 0.083). In the nerve segments whose long axes were not perpendicular to the imaging planes of zC-MRMN, the VSNFs on the axial zC-MRMN images were significantly lower than those on the axial zH-MRMN MPR images that were angled perpendicular to the long axis of the tibial nerve (P < 0.001). CONCLUSIONS: The longitudinal zH-MRMN MPR images clearly displayed the changing features of the intraneural fascicles as well as the gross morphology of the tibial nerves. zH-MRMN can clearly delineate the topography of the tibial nerve fascicles in vivo through use of a 3T MR scanner.


Assuntos
Imageamento por Ressonância Magnética , Nervos Periféricos , Humanos , Nervos Periféricos/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética
5.
Phys Rev Lett ; 129(16): 163602, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36306767

RESUMO

We systematically study the decay of quasi-two-dimensional vortices in an oblate strongly interacting Fermi gas over a wide interaction range and observe that, as the system temperature is lowered, the vortex lifetime increases in the Bose-Einstein condensate (BEC) regime but decreases at unitarity and in the Bardeen-Cooper-Schrieffer (BCS) regime. The observations can be qualitatively captured by a phenomenological model simply involving diffusion and two-body collisional loss, in which the vortex lifetime is mostly determined by the slower process of the two. In particular, the counterintuitive vortex decay in the BCS regime can be interpreted by considering the competition between the temperature dependence of the vortex annihilation rate and that of unpaired fermions. Our results suggest a competing mechanism for the complex vortex decay dynamics in the BCS-BEC crossover for the fermionic superfluids.

6.
Phys Rev Lett ; 126(18): 185302, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34018783

RESUMO

Vortices play a leading role in many fascinating quantum phenomena. Here we generate a large number of vortices by thermally quenching a fermionic superfluid of ^{6}Li atoms in an oblate optical trap and study their annihilation dynamics and spatial distribution. Over a wide interaction range from the attractive to the repulsive side across the Feshbach resonance, these quasi-two-dimensional vortices are observed to follow algebraic scaling laws both in time and space, having exponents consistent with the two-dimensional universality. We further simulate the classical XY model on the square lattice by a Glauber dynamics and find good agreement between the numerical and experimental behaviors. Our work provides a direct demonstration of the universal 2D vortex dynamics.

7.
Pak J Pharm Sci ; 34(3): 1003-1010, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602425

RESUMO

Rhizoma Musa (the Rhizome of Musa basjoo Sied.et Zucc.) is used as a traditional medical herb of Miao nationality in Guizhou province, in China. It has the efficacy of clearing heat and detoxifying, quenching thirst, diuresis, etc. Modern pharmacological studies have shown that it has hypoglycemic, inhibition of α-glucosidase, and anti-inflammatory activity. However, when the rhizomes of Musa basjoo are dug up, the rhizomes are unable regenerate, and the pseudostem and leaf are discarded, which not only pollutes the environment, but also causes a huge waste of herb resources. In this study, a UPLC-ELSD fingerprint analysis with chemometric method was applied for the evaluation of chemical similarity among rhizome, pseudostem and leaf of Musa Basjoo. The results indicated that the combined method could efficiently analyze and compare the chemical similarity among rhizome, pseudostem, and leaf of Musa Basjoo. The proposed method provides the foundation for the resource substitution of the rhizome, pseudostem, and leaf of Musa Basjoo.


Assuntos
Musa/química , Extratos Vegetais/química , Folhas de Planta/química , Rizoma/química , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Medicamentos de Ervas Chinesas , Difusão Dinâmica da Luz , Extratos Vegetais/análise , Caules de Planta/química , Análise de Componente Principal
9.
BMC Cancer ; 19(1): 814, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31419961

RESUMO

BACKGROUND: The co-occurrence of type 1 autoimmune pancreatitis (AIP) and pancreatic tumor (PaT) has been previously reported. Pure AIP cases have favorable prognosis and are primarily treated with steroids, while AIP cases with PaT are associated with poor prognosis where the primary management is pancreatic resection. However, it's a challenge to timely identify the concurrent PaT in AIP because of their similar clinical and radiological manifestations. METHODS: We retrospectively reviewed the data in two medical centers from January 2010 to April 2019. The inclusion criteria were as follows: 1) completion of abdominal CT imaging before invasive procedures to the pancreas, 2) a final diagnosis of type 1 AIP using the 2011 international consensus diagnostic criteria, 3) follow-up duration of at least one month unless AIP and PaT were identified simultaneously. The presence of PaT in AIP was made based on histopathological confirmation, and the absence of PaT in AIP was defined as no pathological or radiological evidence of concurrent PaT. Clinical and radiological characteristics including gender, age, surveillance period, serum IgG4 and Ca-199 levels, biopsy, extrapancreatic involvement, CT and MR (if performed) imaging characteristics were compared between AIP with and without PaT. The Fisher's exact test was used for qualitative variables, and nonparametric Mann-Whitney test for quantitative variables. A p value ≤0.05 was considered statistically significant. RESULTS: A total of 74 patients with type 1 AIP were included, of which 5 (6.7%) had the concurrent PaT. The subtypes were pancreatic ductal adenocarcinoma (3/5), solitary extramedullary plasmacytoma in the pancreas (1/5) and cholangiocarcinoma in the pancreatic segment (1/5), respectively. Gender (p = 0.044), the pattern of pancreatic enlargement (p = 0.003), heterogeneity (p = 0.015), low-density (p = 0.004) on CT and rim enhancement on MRI (p = 0.050) differed significantly between AIP with and without PaT. None of the low-density characteristics on CT or other assessed MRI characteristics could significantly differentiate the two groups (p>0.05). CONCLUSIONS: Female, focal pancreatic enlargement, pancreatic heterogeneity, low-density on CT and rim enhancement on MRI are suggestive of the concurrent PaT in type 1 AIP. The characteristics of low-density on CT or other MRI characteristics did not provide further diagnostic values.


Assuntos
Pancreatite Autoimune/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Pancreatite Autoimune/patologia , Biópsia , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/patologia , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Fatores Sexuais , Tomografia Computadorizada por Raios X , Adulto Jovem
10.
Opt Express ; 26(26): 33756-33763, 2018 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-30650808

RESUMO

We report on the realization of a high-power, ultranarrow-linewidth, and frequency-locked 532 nm laser system. The laser system consists of single-pass and intra-cavity second harmonic generation of a continuous-wave Ytterbium doped fiber laser at 1064 nm in the nonlinear crystal of periodically poled lithium niobate and lithium triborate, respectively. With 47 W infrared input, 30 W green laser is generated through the type I critical phase matching in the intracavity lithium triborate crystal. The laser linewidth is measured to be on the order of sub-kHz, which is achieved by simultaneously locking the single-pass frequency doubling output onto the iodine absorption line R69 (36-1) at 532 nm. Furthermore, the phase locking between the laser system and another slave 1064 nm laser is demonstrated with relative frequency tunability being up to 10 GHz. Our results completely satisfy the requirements of 532 nm laser for quantum simulation with ultracold atoms.

11.
Eur J Vasc Endovasc Surg ; 56(6): 911-917, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30241982

RESUMO

OBJECTIVES: To examine the correlation between computed tomography (CT) features and clinical presentation and to assess the management strategy for patients with isolated superior mesenteric artery (SMA) dissection. MATERIAL AND METHODS: Retrospective analysis of clinical records and CT findings of patients with isolated superior mesenteric artery dissection treated between 2012 and 2016. The relationship between CT features and clinical symptoms and treatment options was studied. Follow up CT images were reviewed and telephone interviews were conducted with patients. RESULTS: Sixty-nine patients with isolated SMA dissection (47 symptomatic and 22 asymptomatic) were evaluated. The dissection length in patients with Sakamoto type IV lesions was significantly longer than that in patients with other lesion types (83.0 ± 40.1 mm, p = .001). Compared with the asymptomatic group, the symptomatic group had longer dissections (63.5 ± 35.9 mm, p < .001) and lesser true lumen diameter (3.1 ± 1.7 mm, p = .044). Fifty-six patients were treated conservatively, of whom 31 showed clinical improvement and exhibited no morphological change during long-term follow up. CONCLUSIONS: In patients with isolated SMA dissection, clinical symptoms were related to the length of dissection and degree of true lumen stenosis. Conservative treatment was commonly employed and yielded favourable outcomes.


Assuntos
Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/terapia , Artéria Mesentérica Superior/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/classificação , Dissecção Aórtica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
J Cell Mol Med ; 21(9): 1732-1741, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28244652

RESUMO

To explore the association of LEP and leptin receptor (LEPR) gene single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.


Assuntos
Povo Asiático/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Leptina/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores para Leptina/genética , Adulto , Estudos de Casos e Controles , Demografia , Feminino , Frequência do Gene/genética , Haplótipos/genética , Humanos , Masculino , Fatores de Risco
13.
Hum Mol Genet ; 24(1): 274-84, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25149475

RESUMO

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR = 0.84, P = 1.00E-08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR = 0.81, P = 2.19E-13) and TMEM187 (rs17422, OR = 0.75, P = 1.47E-15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR = 0.71, P = 2.40E-18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than that in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.


Assuntos
Povo Asiático/genética , Cromossomos Humanos X/genética , Genes Ligados ao Cromossomo X , Lúpus Eritematoso Sistêmico/genética , Ribose-Fosfato Pirofosfoquinase/genética , China , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
14.
Dig Dis Sci ; 62(3): 660-668, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28025745

RESUMO

BACKGROUND: Warburg effect is a hallmark of cancer cells. Accumulating evidence suggests that microRNAs (miRs) could regulate such metabolic reprograming. Aberrant expression of miR-98 has been observed in many types of cancers. However, its functions and significance in colon cancer remain largely elusive. AIMS: To investigate miR-98 expression and the biological functions in colon cancer progression. METHODS: miR-98 expression levels were determined by quantitative RT-PCR in 215 cases of colon cancer samples. miR-98 mimic or inhibitor was used to test the biological functions in SW480 and HCT116 cells, followed by cell proliferation assay, lactate production, glucose uptake, and cellular ATP levels assay and extracellular acidification rates measurement. Western blot and luciferase assay were used to identify the target of miR-98. RESULTS: miR-98 was significantly down-regulated in colon cancer tissues compared to adjacent colon tissues and acted as a suppressor for Warburg effect in cancer cells. miR-98 inhibited glycolysis by directly targeting hexokinase 2, or HK2, illustrating a novel pathway to mediate Warburg effect of cancer cells. In vitro experiments further indicated that HK2 was involved in miR-98-mediated suppression of glucose uptake, lactate production, and cell proliferation. In addition, we detected HK2 expression in colon cancer tissues and found that the expressions of miR-98 and HK2 were negatively correlated. CONCLUSION: miR-98 acts as tumor suppressor gene and inhibits Warburg effect in colon cancer cells, which provided potential targets for clinical treatments.


Assuntos
Reprogramação Celular/fisiologia , Neoplasias do Colo , Hexoquinase/metabolismo , MicroRNAs , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/genética , Glicólise/genética , Células HCT116 , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo
15.
Inflammopharmacology ; 25(2): 203-210, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28190128

RESUMO

OBJECTIVE: In the present study, DNA methylation level of CD4+ T cells exposed to ultraviolet B (UVB) was investigated and its potential mechanisms were also explored. METHODS: CD4+ T cells from 12 cases of healthy subjects and 33 cases of SLE patients were isolated and exposed to different dosages (0, 50, 100 mJ/cm2) of UVB. Further, SLE patients were divided into two groups: active SLE group (22 cases, SLEDAI scores >4) and inactive SLE group (11 cases, SLEDAI scores ≤4). DNA methylation was evaluated by the Methylamp™ Global DNA Methylation Quantification Ultra Kit. The mRNA and protein expression levels of DNA methyltransferases (DNMT1 and DNMT3A) were detected by real-time PCR and western blot, respectively. RESULTS: The levels of DNA methylation and DNMT3A mRNA in SLE patients were significantly decreased compared with those in healthy subjects at baseline. After different dosages of ultraviolet irradiation (0, 50 and 100 mJ/cm2), DNA methylation levels of CD4+ T cells were all reduced in a dose-dependent manner in three subgroups. Additionally, 100 mJ/cm2 ultraviolet irradiation in active SLE group contributed to a significant decrease of both DNA methylation and DNMT3A mRNA levels in CD4+ T cells. UVB exposure had no significant effects on expression levels of DNMT1 mRNA and protein and DNMT3A protein. CONCLUSION: UVB decreases DNA methylation level of CD4+ T cells in SLE patients probably via inhibiting DNMT3A mRNA expression level, which needs to be further explored.


Assuntos
Linfócitos T CD4-Positivos/efeitos da radiação , DNA (Citosina-5-)-Metiltransferases/efeitos da radiação , Metilação de DNA/efeitos da radiação , Lúpus Eritematoso Sistêmico , Raios Ultravioleta , Adulto , Linfócitos T CD4-Positivos/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/fisiologia , DNA Metiltransferase 3A , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Raios Ultravioleta/efeitos adversos
16.
Hum Mol Genet ; 23(2): 524-33, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24001599

RESUMO

Systemic lupus erythematosus (SLE) has a complex etiology and is affected by both genetic and environmental factors. Although more than 40 loci have shown robust association with SLE, the details of these loci, such as the independent contributors and the genes involved, are still unclear. In this study, we performed meta-analysis of two existing genome-wide association studies (GWASs) on Chinese Han populations from Hong Kong and Anhui, China, and followed the findings by further replication on three additional Chinese and Thailand cohorts with a total of 4254 cases and 6262 controls matched geographically and ethnically. We discovered multiple susceptibility variants for SLE in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023, P(_combined) = 1.25E-08, OR = 1.20), DDX6 (rs638893, P(_combined) = 5.19E-07, OR = 1.22) and CXCR5 (rs10892301, P(_combined) = 2.51E-08, OR = 0.85). Genetic contributions from the newly identified variants were all independent of SNP rs4639966, whose association was reported from the previous GWAS. In addition, the three newly identified variants all showed independent association with the disease through modeling by both stepwise and conditional logistic regression. The presence of multiple independent variants in this region emphasizes its role in SLE susceptibility, and also hints the possibility that distinct biological mechanisms might be involved in the disease involving this genomic region.


Assuntos
Cromossomos Humanos Par 11 , RNA Helicases DEAD-box/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lúpus Eritematoso Sistêmico/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Receptores CXCR5/genética , Povo Asiático/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/diagnóstico
17.
Ann Rheum Dis ; 75(5): 891-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25862617

RESUMO

OBJECTIVES: Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility. METHODS: The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction. RESULTS: Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate<0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets. CONCLUSIONS: Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.


Assuntos
Proteínas Ativadoras de 5-Lipoxigenase/genética , Povo Asiático/genética , Antígeno B7-1/genética , Epistasia Genética/genética , Lúpus Eritematoso Sistêmico/genética , Adulto , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Proteínas de Fusão Oncogênica/genética , Polimorfismo de Nucleotídeo Único , Tetraspaninas , Receptor fas/genética
18.
Rheumatology (Oxford) ; 55(12): 2230-2236, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27587881

RESUMO

OBJECTIVE: A recent genome-wide association study identified that genetic variants in DPP4 and CCR6 are connected with a risk of RA in the Han Chinese population. The aim of this study was to estimate the epistatic interaction between DPP4 and CCR6 in RA. METHODS: Two single-nucleotide polymorphisms identified in a Han Chinese genome-wide association study (rs12617656 in DPP4, rs1854853 in CCR6) were genotyped. Logistic regression was used to estimate the multiplicative interaction and the additive interaction was analysed by 2 × 2 factorial design. RESULTS: A total of 1224 subjects (377 RA patients, 847 healthy controls) were included in the initial analysis. Additionally, 600 patients with lupus arthritis were included for comparison. Significant multiplicative interaction between DPP4 and CCR6 was observed in RA [codominant model: odds ratio (OR) = 1.49, P = 0.003]. The epistatic effect seems to be stronger in ACPA-positive RA (codominant model: OR = 1.66, P = 0.001). However, no significant multiplicative interactions were observed in ACPA-negative RA or lupus arthritis. Additive interaction analysis showed a significant epistatic effect, but only in ACPA-positive RA [attributable proportion due to interaction = 0.48 (95% CI 0.10, 0.85)]. A further replication study of an independent cohort (476 subjects) found similar results. Pooled results confirmed that there was significant interaction between DPP4 and CCR6 on both the multiplicative and additive scales. CONCLUSION: The study suggests that a genetic interaction between DPP4 and CCR6 is involved in RA susceptibility. Furthermore, these findings highlight Th17 cell response as an important contributor in the pathogenesis of RA.


Assuntos
Artrite Reumatoide/genética , Dipeptidil Peptidase 4/genética , Epistasia Genética/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores CCR6/genética , Adulto , Idade de Início , Povo Asiático , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Células Th17/imunologia
19.
Cytokine ; 86: 15-20, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27442006

RESUMO

OBJECTIVE: To evaluate the plasma levels of six adipokines, including chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin, in patients with SLE. METHODS: Ninety SLE patients and ninety control subjects were recruited, plasma adipokines levels were measured by enzyme-linked immunosorbent assay, and their associations with major clinical and laboratory indexes were analyzed. RESULTS: There were no significant differences in plasma chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin levels between SLE patients and controls. Further subgroup analyses by major clinical and laboratory indexes showed that plasma omentin-1 level was significantly lower in SLE patients without nephritis when compared with those patients with nephritis (P=0.002). Plasma chemerin, cathepsin-S levels in SLE patients without nervous system disorder were significantly lower in comparison with SLE patients with nervous system disorder (P=0.035, P=0.029). No significant associations of other adipokines with any major clinical and laboratory indexes were observed. CONCLUSIONS: Plasma levels of chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin in SLE patients were not markedly different from the normal controls. The presence of nephritis was connected with higher plasma omentin-1 levels in SLE patients, and the presence of nervous system disorder was associated with higher plasma chemerin, cathepsin-S levels in SLE patients. However, functional studies are awaited to further explore the potential roles of these cytokines in SLE.


Assuntos
Adipocinas/sangue , Lúpus Eritematoso Sistêmico/sangue , Adulto , Catepsinas/sangue , Fator D do Complemento/análise , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Proteínas Ligadas por GPI/sangue , Humanos , Lectinas/sangue , Lipocalina-2/sangue , Nefrite Lúpica/sangue , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Adulto Jovem
20.
Tumour Biol ; 37(9): 11723-11732, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27020591

RESUMO

Ubiquitin-conjugating enzyme E2T (UBE2T) is a member of the E2 family that mediates the ubiquitin-proteasome system and regulates gene expression. It is a major oncogene in several cancers such as lung cancer and breast cancer, while the potential functions of UBE2T in gastric cancer (GC) remains largely unknown. Here, we identified the roles of UBE2T in GC progression and its potential to act as a prognostic marker of GC. Our data demonstrated that UBE2T was significantly upregulated in gastric cancer tissues, and the high expression of UBE2T was significantly correlated with poor differentiation, high T classification, and poor prognosis. In vitro experiments indicated that UBE2T promoted cell proliferation and inhibited cell cycle arrest. In addition, we observed that UBE2T modulated cell mobility by inducing epithelial-mesenchymal transition. Collectively, these findings suggest that UBE2T plays an important role in the tumorigenesis of gastric cancer and could act as a potential independent prognostic factor for cancer therapy.


Assuntos
Neoplasias Gástricas/etiologia , Enzimas de Conjugação de Ubiquitina/fisiologia , Adulto , Idoso , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
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