RESUMO
Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A.â baumannii LPS, four Kdo-containing inner core glycans from A.â baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2â5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A.â baumannii.
Assuntos
Acinetobacter baumannii , Lipopolissacarídeos , Carboidratos , Dissacarídeos/química , Humanos , Lipopolissacarídeos/química , Oligossacarídeos/química , PolissacarídeosRESUMO
BACKGROUND: Bony fusion rate was significantly lower in patients with type 3 Modic change than patients with normal endplates. It is not known whether there are relevant differences in fusion efficiency among patients with type 2 sclerotic Modic change or non-sclerotic Modic change, or no Modic change. METHODS: A retrospective study contained 196 lumbar segments in 123 subjects undergoing posterior lumbar interbody fusion (PLIF) with pedicle screw instrumentation (PSI) to assess the effect of type 2 sclerotic Modic change on fusion efficiency. These endplates were allocated into groups A, B, and C, according to their Modic changes. Group A had endplates with type 2 Modic change and endplate sclerosis. Group B had type 2 Modic change without endplate sclerosis. Group C had neither Modic change nor endplate sclerosis. The presence of Modic change was determined by magnetic resonance imaging (MRI). Endplate sclerosis in type 2 Modic change was detected by computed tomography (CT) before the operation. We collected CT data 3 months to more than 24 months after operation in patients to assess bony fusion. RESULTS: Incidences of bony fusion were 58.8% in group A, 95.0% in group B, 94.3% in group C. The bony fusion rate was significantly lower in group A than in either group B or C. There was no significant difference between groups B and C. Thus, endplates with type 2 sclerotic Modic change had a lower fusion rate in patients undergoing PLIF with PSI. CONCLUSION: Type 2 sclerotic Modic change could be an important factor that affects solid bony fusion in patients undergoing PLIF with PSI. CT may help diagnose endplate sclerosis in patients with type 2 change and inform the choice of the best site for spinal fusion.
Assuntos
Parafusos Pediculares , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Esclerose/diagnóstico por imagem , Esclerose/patologia , Fusão Vertebral/efeitos adversosRESUMO
During the COVID-19 era, Chinese hospitals have developed a system that enables vulnerable cancer patients to continue to receive high-quality medical care, optimising their survival whilst protecting them. This includes use of digital quick codes, fever clinics and optimal scheduling. We wish to share our experiences working with patients during the pandemic.
Assuntos
Betacoronavirus/patogenicidade , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/complicações , Atenção à Saúde/normas , Neoplasias/terapia , Pneumonia Viral/complicações , Guias de Prática Clínica como Assunto/normas , COVID-19 , China , Infecções por Coronavirus/virologia , Europa (Continente) , Humanos , Neoplasias/virologia , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2RESUMO
The aminated mimetics of 2-keto-3-deoxy-sugar acids such as the anti-influenza clinical drugs oseltamivir (Tamiflu) and zanamivir (Relenza) are important bioactive molecules. Development of synthetic methodologies for accessing such compound collections is highly desirable. Herein, we describe a simple, catalyst-free glycal diazidation protocol enabled by visible light-driven conditions. This new method requires neither acid promoters nor transition-metal catalysts and takes place at ambient temperature within 1-2 hours. Notably, the desired transformations could be promoted by thermal conditions as well, albeit with lower efficacy compared to the light-induced conditions. Different sugar acid-derived glycal templates have been converted into a range of 2,3-diazido carbohydrate analogs by harnessing this mild and scalable approach, leading to the discovery of new antiviral agents.
Assuntos
Antivirais/farmacologia , Azidas/farmacologia , Carboidratos/farmacologia , Temperatura Alta , Luz , Rhinovirus/efeitos dos fármacos , Açúcares Ácidos/farmacologia , Zika virus/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , Azidas/síntese química , Azidas/química , Configuração de Carboidratos , Carboidratos/síntese química , Carboidratos/química , Testes de Sensibilidade Microbiana , Açúcares Ácidos/químicaRESUMO
The stereodirecting effect of C5-ester functions on the glycosylation stereoselectivity of 3-deoxy-d- manno-oct-2-ulosonic acid (Kdo) ethyl thioglycoside donors is presented. The coupling of 5- O-arylcarbonyl or acetyl protected Kdo thioglycosides with acceptors proceeds in an α-selective and high-yielding manner, leading to formation of α-linked Kdo glycosides products. On the other hand, the glycosylation stereoselectivity of the 5- O-2-quinolinecarbonyl (Quin) or 4-nitropicoloyl substituted Kdo thioglycoside donors is switchable: (1) The glycosylation of the 5- O-Quin carrying Kdo donors with primary glycosyl acceptors shows complete ß-stereoselectivity, furnishing the corresponding ß-glycosides in good-to-excellent yield. (2) The stereochemical outcome of the secondary acceptors with these Kdo donors is determined mainly by the stereoelectronic nature of the acceptor. Only or predominant α anomeric products are obtained when the Kdo donors couple with the disarmed or highly crowded secondary carbohydrate acceptors, while the selectivity may switch to predominant ß in the glycosylation of the 5- O-4-nitropicoloyl carrying donor with more reactive secondary alcohols. The synthetic use of the newly developed Kdo donors 1c and 7b has been demonstrated by facile preparation of a structurally unique trisaccharide motif 19 which possesses both α- and ß-Kdo glycosidic bonds.
Assuntos
Ácidos Carboxílicos/química , Glicosídeos/síntese química , Açúcares Ácidos/síntese química , Compostos de Sulfidrila/síntese química , Glicosídeos/química , Glicosilação , Estrutura Molecular , Estereoisomerismo , Açúcares Ácidos/química , Compostos de Sulfidrila/químicaRESUMO
Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators-COX-2, iNOS-as well reduced the levels of cytokines-interleukins (IL)-IL-1ß, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.
Assuntos
Demência/tratamento farmacológico , Flavonas/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Intoxicação por MPTP/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Cognição/efeitos dos fármacos , Cognição/fisiologia , Demência/metabolismo , Demência/psicologia , Relação Dose-Resposta a Droga , Flavonas/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/psicologia , Mediadores da Inflamação/metabolismo , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/psicologia , Masculino , Aprendizagem em Labirinto/fisiologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/psicologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-DawleyRESUMO
The first total synthesis of a major component of marine glycolipid vesparioside B ( Scheme 1 , 1, R1 = n-C22H45, R2 = n-C14H29) has been accomplished through a convergent [4 + 3] coupling strategy. Key steps included stereoselective installment of a set of challenging 1,2-cis-glycoside bonds. A 2-quinolinecarbonyl-assisted α-galactosylation and a novel ß-arabinosylation were developed, respectively, to synthesize the α-galactofuranosidic and the ß-arabinopyranosidic linkages. Furthermore, a 4,6-O-benzylidene-controlled α-galactopyranosylation reaction allowed the efficient connection of the left tetrasaccharide donor 2 with the right disaccharide lipid acceptor 3, hence leading to the total synthesis of 1.
Assuntos
Glicoesfingolipídeos/síntese química , Poríferos/química , Animais , Glicoesfingolipídeos/química , Glicosilação , Ligação de Hidrogênio , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
In the establishment of remote sensing information inversion model, the actual measured data of discrete sampling points and the corresponding spectrum data to pixels of remote sensing image, are used to establish the relation, thus to realize the goal of information retrieval. Accurate extraction of spectrum value is very important to establish the remote sensing inversion mode. Converting target spot layer to ROI (region of interest) and then saving the ROI as ASCII is one of the methods that researchers often used to extract the spectral values. Analyzing the coordinate and spectrum values extracted using original coordinate in ENVI, we found that the extracted and original coordinate were not inconsistent and part of spectrum values not belong to the pixel containing the sampling point. The inversion model based on the above information cannot really reflect relationship between the target properties and spectral values; so that the model is meaningless. We equally divided the pixel into four parts and summed up the law. It was found that only when the sampling points distributed in the upper left corner of pixels, the extracted values were correct. On the basis of the above methods, this paper systematically studied the principle of extraction target coordinate and spectral values, and summarized the rule. A new method for extracting spectral parameters of the pixel that sampling point located in the environment of ENVI software. Firstly, pixel sampling point coordinates for any of the four corner points were extracted by the sample points with original coordinate in ENVI. Secondly, the sampling points were judged in which partition of pixel by comparing the absolute values of difference longitude and latitude of the original and extraction coordinates. Lastly, all points were adjusted to the upper left corner of pixels by symmetry principle and spectrum values were extracted by the same way in the first step. The results indicated that the extracted spectrum values of all points were accurate. Experiment on OLI (Operational Land Imager), TM and ETM+ images showed that this method can accurately extract the discrete spectrum value, and as well, clear principle, simple and feasible operation, strong applicability, This paper provides a new idea for remote sensing image extraction of discrete point spectrum.
RESUMO
An efficient methodology for the synthesis of α-Kdo glycosidic bonds has been developed with 5,7-O-di-tert-butylsilylene (DTBS) protected Kdo ethyl thioglycosides as glycosyl donors. The approach permits a wide scope of acceptors to be used, thus affording biologically significant Kdo glycosides in good to excellent chemical yields with complete α-selectivity. The synthetic utility of an orthogonally protected Kdo donor has been demonstrated by concise preparation of two α-Kdo-containing oligosaccharides.
Assuntos
Butanos/química , Glicosídeos/síntese química , Oligossacarídeos/síntese química , Silanos/química , Estereoisomerismo , Tioglicosídeos/química , Glicosídeos/química , Oligossacarídeos/químicaRESUMO
BACKGROUND: Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its' molecular mechanisms controlling cancer cell migration and metastasis are unclear. METHODS: Expression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry. RESULTS: BANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression. CONCLUSION: We determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas B-raf/biossíntese , RNA Longo não Codificante/biossíntese , Animais , Apoptose/genética , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Movimento Celular/fisiologia , Regulação para Baixo , Citometria de Fluxo , Xenoenxertos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica/genética , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Expression of the long non-coding RNA (lncRNA) LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of the present study was to explore the relationship between LOC285194 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC), so as to assess whether it could be a novel biomarker for prognosis and prediction of response to therapy on ESCC patients. METHODS: The method of quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure LOC285194 expression in pretreatment biopsy specimens and matched normal tissue derived from ESCC patients who underwent preoperative chemoradiotherapy followed by surgical resection (CRT + S group; n = 55) or from those who received surgical resection alone (S group; n = 87). The association between LOC285194 expression and clinicopathological features and prognosis were then analyzed. RESULTS: LOC285194 expression was significantly down-regulated in ESCC tumor tissues when compared with the adjacent normal tissues (p < 0.001). Low expression of LOC285194 was associated with larger tumor size (p = 0.002), advanced TNM stage (p = 0.018), more lymph node metastases (p = 0.013) and distant metastases (p = 0.015). In the CRT + S group, the pathological complete response rate was 57% (16/28) for the LOC285194-high group, and 15% (4/27) for the LOC285194-low group. Univariate analysis revealed that low expression of LOC285194 was significantly correlated with CRT response (p = 0.002). Moreover, Kaplan-Meier survival analysis revealed that patients with low expression of LOC285194 had a decreased disease free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Multivariable analysis further identified low expression of LOC285194 as an independent prognosis factor for CRT response (p = 0.011), DFS (p < 0.001) and OS (p = 0.002). CONCLUSION: Decreased expression of LOC285194 could serve as a molecular marker to predict the clinical outcome of ESCC patients after surgery, and select patients who would benefit from preoperative CRT.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , RNA Longo não Codificante/genética , Tolerância a Radiação/genética , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Regulação para Baixo/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Feminino , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Células Tumorais CultivadasRESUMO
We describe in this paper the tuning effect of silyl protecting groups on the donor reactivity of galactofuranosyl phenyl thioglycosides. Silyl ethers on the galactofuranose ring are found to have an arming effect on the glycosylation reactivity, but the cyclic 3,5-acetal protecting group decreases the reactivity. The reactive phenyl 2,6-di-O-Bz-3,5-di-O-TBS-1-thio-ß-d-galactofuranoside 3 is proved to be a useful glycosyl building block. By taking advantage of this donor, we achieved the highly efficient one-pot solution-phase assembly of a panel of ß-d-galactofuranosyl tri- and tetrasaccharides possessing diverse glycosidic linkages.
Assuntos
Éteres/química , Oligossacarídeos/síntese química , Silanos/química , Tioglicosídeos/síntese química , Glicosilação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Oligossacarídeos/química , Tioglicosídeos/químicaRESUMO
Acinetobacter baumannii poses a serious threat to human health. Pathogenic bacterial lipopolysaccharides (LPSs) are potent immunogens for the development of antibacterial vaccines. To investigate the antigenic properties of A. baumannii LPS, five well-defined core oligosaccharide fragments from the LPS of A. baumannii SMAL and ATCC 19606 were synthesized. A divergent synthesis strategy based on orthogonally protected α-(2 â 5)-linked Kdo dimer 6 was developed. Selective exposure of different positions in this key precursor and then elongation of sugar chains via stereocontrolled formation of both 1,2-trans and 1,2-cis-2-aminoglycosidic linkages permitted the efficient synthesis of the targets. The synthetic route also highlights a 4-O and then 7-O glycosylation sequence for assembly of the novel 4,7-branched Kdo framework. Antigenicity assay using the glycan microarray technique disclosed that tetrasaccharide 3 featuring both 4,7-branch and α-(2 â 5)-Kdo-Kdo structural elements was a potential antigenic determinant.
Assuntos
Acinetobacter baumannii , Lipopolissacarídeos , Oligossacarídeos , Acinetobacter baumannii/química , Acinetobacter baumannii/imunologia , Lipopolissacarídeos/química , Lipopolissacarídeos/imunologia , Oligossacarídeos/química , Oligossacarídeos/síntese química , Glicosilação , Estrutura Molecular , Sequência de Carboidratos , HumanosRESUMO
A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include the highly stereoselective construction of ß-3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and two 1,2-cis-glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired ß-Kdo glycoside and 1,2-cis-α-l-fucoside/d-glucoside. Moreover, the key branched framework was successfully established through a [(7 + 1) + 1] assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.
Assuntos
Glicosídeos , Lipopolissacarídeos , Lipopolissacarídeos/química , Glicosídeos/químicaRESUMO
We describe in this paper the efficient four-component one-pot synthesis of three fully protected oligosaccharides 22, 36, and 50 with di-branched structures by employing D-galacto- and mannopyranosyl thioglycoside diols as central glycosylating agents. After global deprotection, they were converted respectively into the 3-aminopropyl linker-containing free oligosaccharide fragments 14, 24, and 38 structurally related to cell wall oligosaccharides from Atractylodes lancea DC, the marine fungus Lineolata rhizophorae and pathogenic Mycobacterium tuberculosis. The 3-aminopropyl linker at the anomeric carbon can enable conjugation of these synthetic oligomers to a suitable protein carrier.
Assuntos
Galactose/química , Manose/química , Oligossacarídeos/química , Oligossacarídeos/síntese química , Tioglicosídeos/química , Técnicas de Química Sintética , Glicosilação , Estereoisomerismo , Especificidade por SubstratoRESUMO
In order to illustrate the three-dimension spatial variability of soil salinity in central China flood area of the Yellow river, integrated soil sampling data and remote sensing data, spectral indices and inverse distance weighting (IDW) method were applied to the estimation and simulation of three-dimension spatial distribution of soil salinity. The study was carried out in typical central China flood area of the Yellow river in Fengqiu County, Henan Province, China. The electrical conductivity of the saturation extract (EC1: 5) of 505 soil samples collected at 101 points was measured. The results indicated that the coefficient of variation of soil salinity at each soil layer is from 0.218 to 0.324 and exhibited the moderate spatial variability. The average of soil electrical conductivity is from 0.121 to 0.154 ds x m(-1). The 2 820 three-dimension spatial scattered data for soil electrical conductivity were taken at soil salinity mapping interpreted by spectral indices and soil electrical conductivity. Three-dimension IDW interpolation showed that a large area of high soil salinity mainly located in the region of Tianran canal and the along of the Yellow river. The shape of the soil salinity profile was downward flowed, revealing soil salinity increasing with depth in whole soil profile and soil salinity accumulated in the subsoil. The accuracy of the predictions was tested using 20 soil sampled points. The root mean square error (RMSE) of calibration for three-dimension distribution of soil salinity showed that the IDW method based on spectral indices was ideal. The research results can provide theoretical foundations to the management and utilization of salt-affected land in China flood area, especially in the Yellow river zone.
RESUMO
OBJECTIVE: Complications related to triceps after total elbow arthroplasty (TEA) have become a major surgical concern. The triceps-preserving approach has the advantage of not disturbing the insertion of triceps but is disadvantaged by the reduced exposure of the elbow joint. The aim of this study was to investigate the clinical and radiological outcomes of TEA with a triceps-preserving approach and to compare the outcomes of TEA to treat arthropathy with that of TEA to treat acute distal humerus fracture. METHODS: From January 2010 to December 2018, 23 patients undergoing primary TEAs were retrospectively reviewed with a mean follow-up time of 92.6 months (range, 52-136 months). Each TEA was performed using the triceps-preserving approach with a semi-constrained Coonrad-Morrey prosthesis. Patient demographics, range of motion (ROM), pain visual analogue scale (VAS), and triceps strength (Medical Research Council [MRC] scale) were compared before and after surgery. The Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, radiographic outcome, and complications were evaluated at follow-up. RESULTS: In total, seven males and 16 females were included in this study, with a mean age of 66.1 years (range:46-85 years). By the last follow-up, pain had been significantly relieved in all patients. The average MEPS in the arthropathy group and fracture group were 90.8 ± 10.3 points (range: 68-98 points) and 91.7 ± 0.4 (range: 76-100 points), respectively. The average DASH of the arthropathy group and fracture group was 37.3 ± 18.8 points (range: 18-52 points) and 38.4 ± 20.1 (range: 16-60 points). At the last follow-up after surgery, the mean flexion arcs in the arthropathy group and fracture group were 100.4° ± 24.1° and 97.8° ± 28.1°, respectively. The mean pro-supination arcs in the arthropathy group and fracture group were 142.4° ± 15.2° and 139.2° ± 17.5°, respectively. There were no significant differences in clinical outcomes between the two groups (P ≥ 0.05). Triceps strength was normal (MRC grade V) in 15 elbows and good in eight elbows. None of the cases experienced weakness of the triceps strength, infection, periprosthetic fractures, or prosthesis breakage. CONCLUSIONS: The clinical and radiographical outcomes of TEA with the triceps-preserving approach were satisfactory in patients with distal humerus fracture, osteoarthritis and rheumatoid arthritis.
Assuntos
Artrite Reumatoide , Artroplastia de Substituição do Cotovelo , Articulação do Cotovelo , Idoso , Feminino , Humanos , Masculino , Braço/cirurgia , Artrite Reumatoide/cirurgia , Cotovelo/cirurgia , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/cirurgia , Seguimentos , Próteses e Implantes , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs (~22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating gene expression. Although miR-196a has been implicated in several other cancers, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of miR-196a in NSCLC and its clinical significance, as well as its biological role in tumor progression. METHODS: Expression of miR-196a was analyzed in 34 NSCLC tissues and five NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of DNA methylation on miR-196a expression was investigated by 5-aza-2-deoxy-cytidine treatment and bisulfite sequencing. The effect of miR-196a on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Analysis of target protein expression was determined by western blotting. Luciferase reporter plasmids were constructed to confirm the action of miR-196a on downstream target genes, including HOXA5. Differences between the results were tested for significance using Student's t-test (two-tailed). RESULTS: miR-196a was highly expressed both in NSCLC samples and cell lines compared with their corresponding normal counterparts, and the expression of miR-196a may be affected by DNA demethylation. Higher expression of miR-196a in NSCLC tissues was associated with a higher clinical stage, and also correlated with NSCLC lymph-node metastasis. In vitro functional assays demonstrated that modulation of miR-196a expression affected NSCLC cell proliferation, migration and invasion. Our analysis showed that miR-196a suppressed the expression of HOXA5 both at the mRNA and protein levels, and luciferase assays confirmed that miR-196a directly bound to the 3'untranslated region of HOXA5. Knockdown of HOXA5 expression in A549 cells using RNAi was shown to promote NSCLC cell proliferation, migration and invasion. Finally, we observed an inverse correlation between HOXA5 and miR-196a expression in NSCLC tissues. CONCLUSIONS: Our findings indicate that miR-196a is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell proliferation, migration and invasion, partially via the down-regulation of HOXA5. Thus, miR-196a may represent a potential therapeutic target for NSCLC intervention.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Homeodomínio/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Apoptose/fisiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Metilação de DNA , Técnicas de Silenciamento de Genes , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Pulmonares/metabolismo , MicroRNAs/biossíntese , MicroRNAs/genética , Invasividade Neoplásica , Regulação para CimaRESUMO
We describe in this paper the development of a novel diastereoselective cyclic imine cycloaddition strategy to access the polyhydroxylated indolizidine skeleton and its application in the concise syntheses of (+)-/(-)-lentiginosines and (-)-2-epi-steviamine.
Assuntos
Alcaloides/química , Alcaloides/síntese química , Iminas/química , Imino Açúcares/química , Imino Açúcares/síntese química , Indolizidinas/química , Reação de Cicloadição , Indolizidinas/síntese química , Estrutura Molecular , EstereoisomerismoRESUMO
We describe in this paper the development of a novel regioselective furanosylation methodology using partially protected furanosyl thioglycosides as central glycosylating building blocks and its application in the efficient one-pot synthesis of a series of linear and branched-type arabino- and galactofuranoside fragments structurally related to the cell wall polysaccharides of Mycobacterium tuberculosis , Streptococcus pneumoniae serostype 35A, and sugar beet.