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1.
Clin Infect Dis ; 78(6): 1531-1535, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38170452

RESUMO

Within a multistate clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among nonhospitalized patients with SARS-CoV-2 with risk factors for severe COVID-19. Among 3247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Humanos , Antivirais/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Idoso , Fatores de Risco , Ritonavir/uso terapêutico , COVID-19/epidemiologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/uso terapêutico , Alanina/análogos & derivados , Padrões de Prática Médica/estatística & dados numéricos , Citidina/análogos & derivados , Hidroxilaminas
2.
J Pediatr Neurosci ; 17(Suppl 1): S21-S28, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36388007

RESUMO

Three-dimensional (3D) photography is becoming more common in craniosynostosis practice and may be used for research, archiving, and as a planning tool. In this article, an overview of the uses of 3D photography will be given, including systems available and illustrations of how they can be used. Important innovations in 3D computer vision will also be discussed, including the potential role of statistical shape modeling and analysis as an outcomes tool with presentation of some results and a review of the literature on the topic. Potential future applications in diagnostics using machine learning will also be presented.

3.
Comput Intell Neurosci ; 2022: 3905998, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795762

RESUMO

In order to achieve efficient and accurate breast tumor recognition and diagnosis, this paper proposes a breast tumor ultrasound image segmentation method based on U-Net framework, combined with residual block and attention mechanism. In this method, the residual block is introduced into U-Net network for improvement to avoid the degradation of model performance caused by the gradient disappearance and reduce the training difficulty of deep network. At the same time, considering the features of spatial and channel attention, a fusion attention mechanism is proposed to be introduced into the image analysis model to improve the ability to obtain the feature information of ultrasound images and realize the accurate recognition and extraction of breast tumors. The experimental results show that the Dice index value of the proposed method can reach 0.921, which shows excellent image segmentation performance.


Assuntos
Neoplasias da Mama , Recuperação Demorada da Anestesia , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Ultrassonografia/métodos
4.
Acta Diabetol ; 59(5): 661-673, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34978596

RESUMO

AIMS: White adipose tissue (WAT) dysfunction has been associated with adipose tissue low-grade inflammation and oxidative stress leading to insulin resistance (IR). Adrenomedullin (ADM), an endogenous active peptide considered as an adipokine, is associated with adipocytes function. METHODS: We evaluated the protective effects of ADM against IR in 3T3-L1 adipocytes treated by palmitic acid (PA) and in visceral white adipose tissue (vWAT) of obese rats fed with high-fat diet. RESULTS: We found that endogenous protein expressions of ADM and its receptor in PA-treated adipocytes were markedly increased. PA significantly induced impaired insulin signaling by affecting phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) axis and glucose transporter-4 (GLUT-4) levels, whereas ADM pretreatment enhanced insulin signaling PI3K/Akt and GLUT-4 membrane protein levels, decreased pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß) and IL-6 levels, and improved oxidative stress accompanied with reduced reactive oxygen species (ROS) levels and increased anti-oxidant enzymes manganese superoxide dismutase 2 (SOD2), glutathione peroxidase (GPx1) and catalase (CAT) protein expressions. Furthermore, ADM treatment not only improved IR in obese rats, but also effectively restored insulin signaling, and reduced inflammation and oxidative stress in vWAT of obese rats. CONCLUSIONS: This study demonstrates a prevention potential of ADM against obesity-related metabolic disorders, due to its protective effects against IR, inflammation and oxidative stress in adipocytes.


Assuntos
Resistência à Insulina , Proteínas Proto-Oncogênicas c-akt , Adipócitos/metabolismo , Adrenomedulina/metabolismo , Adrenomedulina/farmacologia , Animais , Inflamação/metabolismo , Insulina/metabolismo , Obesidade/metabolismo , Ácido Palmítico/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinase/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
5.
J Healthc Eng ; 2021: 1141619, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721822

RESUMO

Early diagnosis of tumor plays an important role in the improvement of treatment and survival rate of patients. However, breast tumors are difficult to be diagnosed by invasive examination, so medical imaging has become the most intuitive auxiliary method for breast tumor diagnosis. Although there is no universal perfect method for image segmentation so far, the consensus on the general law of image segmentation has produced considerable research results and methods. In this context, this paper focuses on the breast tumor image segmentation method based on CNN and proposes an improved DCNN method combined with CRF. This method can obtain the information of multiscale and pixels better. The experimental results show that, compared with DCNN without these methods, the segmentation accuracy is significantly improved.


Assuntos
Neoplasias da Mama , Lógica Fuzzy , Algoritmos , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética
6.
BMC Cardiovasc Disord ; 21(1): 495, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645391

RESUMO

BACKGROUND: Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (H2S) can prevent AMC in rats with diabetic nephropathy (DN). METHODS: DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague-Dawley rats for 8 weeks. RESULTS: Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a H2S donor, 50 µmol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous H2S generating enzyme activity and protein expression of cystathionine-γ-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-ß1 protein level, and improved aortic elastin expression. CONCLUSIONS: H2S may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-ß1 level and increasing local elastin level.


Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Nefropatias Diabéticas/tratamento farmacológico , Sulfeto de Hidrogênio/farmacologia , Túnica Média/efeitos dos fármacos , Calcificação Vascular/prevenção & controle , Animais , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/etiologia , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Catepsinas/metabolismo , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Elastina/metabolismo , Masculino , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Túnica Média/metabolismo , Túnica Média/patologia , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia
7.
Sci Total Environ ; 772: 145622, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33770868

RESUMO

The integrated control of multiple pollutants is a promising approach for efficient and economical pollution reduction. Inspired by the simultaneous removal of SO2 and NOx by the spray-and-scattered-bubble (SSB) technology, this paper further explores gas phase arsenic and selenium removal ability of this new technology. Ammonia concentration, SO2 concentration, liquid/gas ratio and immersion depth, which are the key operating parameters of SSB technology, are evaluated to determine their effect on arsenic and selenium removal. The experimental results indicate that ammonia concentration and SO2 will facilitate the simultaneous removal of arsenic and selenium by SSB technology. However, the excess ammonia concentration and SO2 should avoided to prevent the decrease in removal efficiency caused by the ammonia escape, increased mass transfer resistance, and mechanical carry-over. The maximum removal efficiency for arsenic can be obtained at the liquid-gas ratio of 10 L/m3, and for selenium, the maximum removal efficiency will be reached at 14 L/m3. For the technology of spray-and-scattered-bubble, chemical reaction and mass transfer jointly play the role in contaminant removal. By changing the immersion depth and measuring the corresponding pressure drop, the weight assigned to the effect of chemical reaction and mass transfer effect could be ascertained to a certain degree. It is speculated that chemical reaction will play a more important role for selenium removal in the bubble zone than the mass transfer. Moreover, for arsenic, mass transfer effect will play a more important role than chemical reaction. The sensitivity analysis for simultaneous removal of arsenic and selenium by SSB technology indicating that the variation of operating conditions will lead to a greater change in arsenic removal as compared with selenium.

8.
Obesity (Silver Spring) ; 29(1): 86-97, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32985779

RESUMO

OBJECTIVE: Adrenomedullin (ADM) possesses therapeutic potential for inflammatory diseases. Consequently, the effects of ADM on inflammation in visceral white adipose tissue (vWAT) of obese rats or in adipocytes were explored in this study. METHODS: Male rats were fed a high-fat diet for 12 weeks to induce obesity, and obese rats were implanted with osmotic minipumps providing constant infusion of ADM (300 ng/kg per hour) and continued to be fed a high-fat diet for 4 weeks. RESULTS: When compared with the control group, endogenous protein expression of ADM and ADM receptors in vWAT and in lipopolysaccharide (LPS)-treated adipocytes was markedly increased. ADM significantly decreased the protein expression of the inflammatory mediators TNFα, IL-1ß, cyclooxygenase-2, and inducible nitric oxide synthase in vWAT of obese rats and in adipocytes stimulated by LPS. It also inhibited the activation of the inflammatory signaling pathways MAPK and NF-κB induced by LPS in adipocytes. These effects of ADM in adipocytes were inhibited by the administration of ADM receptor antagonist and cAMP-dependent protein kinase (PKA) activation inhibitor. CONCLUSIONS: ADM can inhibit inflammation in WAT in obesity, which may be mediated by the activation of ADM receptors and PKA.


Assuntos
Tecido Adiposo Branco/metabolismo , Adrenomedulina/metabolismo , Mediadores da Inflamação/metabolismo , Células 3T3 , Adipócitos/metabolismo , Animais , Proteína C-Reativa/análise , Ciclo-Oxigenase 2/metabolismo , Dieta Hiperlipídica , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Obesidade/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Adrenomedulina/antagonistas & inibidores , Transdução de Sinais , Fator de Necrose Tumoral alfa/sangue
9.
Neuropeptides ; 85: 102109, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33253929

RESUMO

Inflammation plays a critical role in the development of neurodegenerative diseases. Adrenomedullin 2 (AM2), a member of the calcitonin gene-related peptide family, has been known to have anti-inflammatory effects. Here, we evaluated the anti-inflammatory effects of AM2 in LPS-activated microglia and BV2 cells. The endogenous mRNA and protein expressions of AM2, calcitonin receptor-like receptor (CLR), receptor activity-modifying proteins (RAMPs) including RAMP1, RAMP2 and RAMP3 and the production of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were detected by RT-PCR and Western blot. Our results revealed that LPS (1 µg/mL) significantly stimulated CLR, RAMP1, RAMP2 and RAMP3 protein expressions in BV2 microglia cells, but AM2 had a significant decrease. However, the mRNA levels of AM2, CLR, and RAMP1/2/3 were all markedly increased. LPS also induced obvious increases in mRNA and protein levels of the inflammatory mediators (TNF-α, IL-1ß, COX2 and iNOS). More importantly, AM2 (10 nM) administration effectively inhibited the mRNA and protein expressions of these mediators induced by LPS and increased the cAMP content in LPS-stimulated BV2 cells. Furthermore, the antagonism with AM2 receptor antagonist IMD17-47, adrenomedullin (AM) receptor antagonist by AM22-52 or the inhibition of protein kinase A (PKA) activation by P1195 effectively prevented the inhibitory role of AM2 in LPS-induced production of the above inflammatory mediators. In conclusion, AM2 inhibits LPS-induced inflammation in BV2 microglia cells that may be mainly through AM receptor-mediated cAMP-PKA pathway. Our results indicate AM2 plays an important protective role in microglia inflammation, suggesting therapeutic potential for AM2 in neuroinflammation diseases caused by activated microglia.


Assuntos
Inflamação/metabolismo , Microglia/metabolismo , Transdução de Sinais , Animais , Células Cultivadas , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/administração & dosagem , Ratos Sprague-Dawley , Receptores de AMP Cíclico/metabolismo
10.
J Transl Med ; 17(1): 256, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391086

RESUMO

BACKGROUND: The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in the paraventricular nucleus (PVN) involves sympathetic abnormality in some cardiovascular diseases such as hypertension. This study was designed to explore the effects of tumor necrosis factor alpha (TNFα) in the PVN on the AAR and SNA in rats with obesity-related hypertension (OH) induced by a high-fat diet for 12 weeks. METHODS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded in anesthetized rats, and their responses to capsaicin (CAP) stimulation of the right inguinal white adipose tissue were used to evaluate the AAR. RESULTS: Compared to the control rats, the systolic blood pressure (SBP), plasma norepinephrine (NE, indicating SNA) and TNFα levels, TNFα mRNA and protein levels, reactive oxygen species (ROS) content and NADPH oxidase activity in the PVN were significantly elevated in rats with OH. TNFα in the PVN markedly enhanced sympathoexcitation and AAR. Moreover, the enhancement of AAR caused by TNFα can be significantly strengthened by the pretreatment of diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, but attenuated by TNF-α receptor antagonist R-7050, superoxide scavenger PEG-SOD and NADPH oxidase inhibitor apocynin (Apo) in rats with OH. Acute microinjection of TNF-α into the PVN significantly increased the activity of NADPH oxidase and ROS levels in rats with OH, which were effectively blocked by R-7050. Furthermore, our results also showed that the increased levels of ROS, TNFα and NADPH oxidase subunits mRNA and protein in the PVN of rats with OH were significantly reversed by pentoxifylline (PTX, 30 mg/kg daily ip; in 10% ethanol) application, a cytokine blocker, for a period of 5 weeks. PTX administration also significantly decreased SBP, AAR and plasma NE levels in rats with OH. CONCLUSIONS: TNFα in the PVN modulates AAR and contributes to sympathoexcitation in OH possibly through NADPH oxidase-dependent ROS generation. TNFα blockade attenuates AAR and sympathoexcitation that unveils TNFα in the PVN may be a possible therapeutic target for the intervention of OH.


Assuntos
Tecido Adiposo/metabolismo , Dieta Hiperlipídica , Obesidade/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Tecido Adiposo Branco/patologia , Adiposidade , Animais , Peso Corporal , Inflamação/metabolismo , Masculino , NADPH Oxidases/metabolismo , Neurônios Aferentes/metabolismo , Norepinefrina/sangue , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sistema Nervoso Simpático/patologia , Sístole , Fator de Necrose Tumoral alfa/sangue
11.
Biomed Res Int ; 2018: 5201786, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30581856

RESUMO

This study intended to improve physiological characteristics of Magnolia officinalis bark (MOB) extracts by Aspergillus niger fermentation. M. officinalis bark was extracted using distilled water, 95% ethanol, and methanol, and it was then fermented by A. niger. The physiological characteristics of the fermented extracts, namely, tyrosinase inhibitory activity, antioxidant activity, antibacterial activity, and anti-skin-aging activity, were evaluated and compared with those of unfermented extracts. To determine the safety of the fermented extracts, their cytotoxicity was analyzed by measuring the cell viability of CCD-966SK and human epidermal melanocytes (HEMn) after exposure. The fermented methanol extract exhibited the highest antityrosinase activity, total phenolic content, and antioxidant activity. The total phenolic content of the extracts fermented by A. niger was 3.52 times greater than that of the unfermented extracts. The optimal IC50 values for tyrosinase inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH) removal by the A. niger-fermented extracts were 30 and 12 µg/mL, respectively. The fermented methanol extracts inhibited skin-aging-related enzymes such as collagenase, elastase, MMP-1, and MMP-2. Compared with the unfermented extracts, the fermented extracts also contained greater antibacterial activity against tested stains including MRSA. These results could be attributed to an increase in the concentration of original active compounds and the biosynthesis of new compounds during fermentation. In cytotoxicity assays, the A. niger-fermented extracts were nontoxic to CCD-966SK cells, even at 500 µg/mL. Hence, in general, methanol-extracted M. officinalis fermented by A. niger for 72 h has the most active antioxidant, skincare, or antiaging compounds for healthy food or cosmetics applications.


Assuntos
Envelhecimento/efeitos dos fármacos , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Aspergillus niger/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Magnolia/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Compostos de Bifenilo/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Epidérmicas/efeitos dos fármacos , Humanos , Melanócitos/efeitos dos fármacos , Picratos/farmacologia , Extratos Vegetais/farmacologia
12.
EBioMedicine ; 33: 94-104, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29936139

RESUMO

Immunotherapeutic agents have demonstrated encouraging signs of clinical utility in non-Hodgkin lymphoma. The goal of this study is to analyze the immune characteristics of Chinese patients with diffuse large B-cell lymphoma (DLBCL) to inform the development of immunotherapies in this patient population. Tumor samples from 211 DLBCL patients were analyzed for cell of origin (COO) and immune characteristics using the NanoString platform as well as MYC protein expression through immunohistochemistry. Lower incidence of the germinal center B-cell (GCB) subtype (93/211, 44.1%) was observed in this cohort. Compared to the GCB subtype, the activated B-cell (ABC) subtype was associated with significantly increased expression of multiple pro-inflammatory gene signatures and decreased expression of anti-inflammatory gene signatures. Instead of affecting the pro-inflammatory genes, MYC protein overexpression showed a negative correlation with the expression of T-cell receptor (TCR) and T regulatory genes as well as the OX40 gene. Regardless of COO, higher PD-L1 or IDO1 gene expression correlated with increased expression of T effector and Interferon-γ gene signatures while the expression of multiple oncogenes including ACTR3B, ERBB2, AKT2 and SMARCD1 was down-regulated. Our findings may thus be helpful in guiding further development of immunotherapies for the different subsets of Chinese DLBCL patients.


Assuntos
Antígeno B7-H1/genética , Centro Germinativo/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Linfoma Difuso de Grandes Células B/imunologia , Ligante OX40/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Adolescente , Adulto , Idoso , China , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-myc/genética , Regulação para Cima , Adulto Jovem
13.
Int J Syst Evol Microbiol ; 68(4): 1390-1395, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29509133

RESUMO

Two strains of Gram-stain-negative, facultatively anaerobic short-rod bacteria were recovered from two different food samples in Ma'anshan city, Anhui province, China in 2008. The bacteria were characterized in a polyphasic taxonomic study that included phenotypic, phylogenetic and genotypic methodologies. Phylogenetic analysis of the 16S rRNA gene demonstrated that the two strains belonged to the genus Proteus and were most similar to Proteus vulgaris ATCC 29905T with a score of 99.7 %. Phylogenetic analysis of the rpoB gene placed the two strains into a cluster with a distinctly interspecies phylogenetic branch that was clearly separated from six type strains of the genus Proteus, with the most closely related species being Proteus mirabilis ATCC 29906T. In silico genomic comparisons, including in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI) analysis showed that the representative strain, 08MAS0041T, and all six Proteus species share less than 70 % isDDH and have a 95 % ANI cutoff level, supporting the designation of the two strains as a novel species of the genus Proteus. The predominant cellular fatty acids of strain 08MAS0041T were C16 : 0 (24.8 %), C16 : 1ω7c/16 : 1ω6c (16.5 %), C18 : 1ω6c/C18 : 1ω7c (14.5 %), C17 : 0 cyclo (12.6 %) and C16 : 1iso I/C14 : 0 3-OH (10.6 %). The analysis of biochemical, phylogenetic and genomic data confirmed that the two strains were clearly different from all recognized species of the genus Proteus and represent a novel Proteus species, for which the name Proteus alimentorum sp. nov. is proposed. The type strain is 08MAS0041T (=DSM 104685T=CGMCC 1.15939T).


Assuntos
Filogenia , Proteus/classificação , Carne Vermelha/microbiologia , Alimentos Marinhos/microbiologia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Nephropidae , Hibridização de Ácido Nucleico , Proteus/genética , Proteus/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Suínos
14.
Cancer Immunol Immunother ; 67(3): 471-481, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29214427

RESUMO

The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mutação , PTEN Fosfo-Hidrolase/genética , Análise Serial de Tecidos/normas , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Coortes , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
15.
Molecules ; 22(11)2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29135958

RESUMO

Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, ß-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR) analysis indicated that introduction of α, ß-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Técnicas de Química Sintética , Desenho de Fármacos , Modelos Moleculares , Quinolizinas/química , Quinolizinas/farmacologia , Alcaloides/síntese química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA/química , Relação Dose-Resposta a Droga , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Estrutura Molecular , Quinolizinas/síntese química , Relação Estrutura-Atividade , Matrinas
16.
Oncol Rep ; 36(5): 3014-3022, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27667116

RESUMO

To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia­associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia­induced activation of the renin­angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy­lysosome as well as ubiquitin­proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti­cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin-proteasome pathway (UPP).


Assuntos
Amidas/administração & dosagem , Caquexia/tratamento farmacológico , Caquexia/patologia , Neoplasias do Colo/tratamento farmacológico , Fumaratos/administração & dosagem , Animais , Autofagia/efeitos dos fármacos , Caquexia/genética , Linhagem Celular Tumoral , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Estresse Oxidativo/efeitos dos fármacos , Renina/antagonistas & inibidores , Sistema Renina-Angiotensina/efeitos dos fármacos
17.
Tumour Biol ; 37(5): 5885-95, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26589417

RESUMO

Increasing results suggest microRNAs (miRNAs) could function important roles in malignant tumor progression. miR-30a-5p is downregulated in variety of cancers and acts as a cancer suppressing gene. The functions and molecular mechanisms of miRNA-30a-5p in hepatocellular carcinoma (HCC) remain unclear. In the present study, quantitative real-time PCR (qRT-PCR) was used to detect miR-30a-5p expression in 16 pairs of HCC and their adjacent non-cancerous tissues and HCC cell lines. By overexpression of miRNA-30a-5p, CCK-8 and colon formation assay were used to evaluate cell growth and flow cytometry to evaluate cell apoptosis. Western blot was used to test protein expression. And potential mechanisms were analyzed with luciferase activity assay. In vivo HepG2 tumor growth was observed with nude mice. Our results showed that miR-30a-5p expression in HCC tissues was significantly lower compared to adjacent non-cancerous liver tissues, and lower miR-30a-5p expression was also observed in HCC cell lines compared to normal liver cell. Luciferase assay showed that metadherin (MTDH) mRNA was a direct target of miR-30a-5p. A significant reverse correlation between miR-30a-5p and MTDH in liver cancer tissues was observed. miR-30a-5p overexpression in HCC cells significantly inhibited cell proliferation, colon formation, and induced apoptosis while MTDH overexpression reversed growth inhibition and apoptosis induction of miRNA-30a-5p in HCC cells. miRNA-30a-5p upregulated phosphatase and tensin homolog (PTEN) protein expression and thus inhibited AKT activating by targeting MTDH. miRNA-30a-5p also significantly inhibited HepG2 tumor growth in vivo. Our results suggest that underexpression of miR-30a-5p might function as a tumor suppressing miRNA by directly targeting MTDH in HCC and is therefore a potential candidate biomarker for HCC targeting therapy.


Assuntos
Moléculas de Adesão Celular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA , Regiões 3' não Traduzidas , Animais , Apoptose/genética , Sequência de Bases , Sítios de Ligação , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Membrana , Camundongos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/química , RNA Mensageiro/genética , Proteínas de Ligação a RNA , Transdução de Sinais , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Int J Mol Sci ; 16(8): 19419-32, 2015 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-26287185

RESUMO

The activation of oncogenes and the loss of tumor suppressor genes are believed to play critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). Metaherin(MTDH), also called astrocyte elevated gene-1 (AEG-1), is frequently amplified in a variety of cancers, but the roles of MTDH with regard to growth and apoptosis in HCC have not yet been studied. In the present study, we first analyzed the expression of MTDH in HCC samples. We found that MTDH protein levels are higher in most HCC cancerous tissues compared with their matched adjacent non-tumor tissues. Additionally, the MTDH mRNA was also higher inHCC tissues compared to their matched adjacent non-tumor tissues. Knockdown of the endogenous MTDH using small interfering RNA further showed that deficiency of MTDH suppressed cell growth and caused apoptosis in HCC cells. Knockdown MTDH promoted PTEN and p53 expression in HCC cells and inhibited AKT phosphorylation. Knockdown MTDH also inhibited tumor growth in vivo. All these results indicated that MTDH protein levels in most HCC tissues are higher than non-tumor tissues, and knockdown of MTDH inhibited growth and induced apoptosis in HCC cells through the activation of PTEN.Therefore, MTDH might be an effective targeted therapy gene for HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Moléculas de Adesão Celular/genética , Neoplasias Hepáticas/terapia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/uso terapêutico , Transdução de Sinais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células , Células Hep G2 , Humanos , Lentivirus/genética , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Membrana , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA , Terapêutica com RNAi
19.
Int J Syst Evol Microbiol ; 65(7): 2130-2134, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25851592

RESUMO

The taxonomic position of a group of seven closely related lactose-negative enterobacterial strains, which were isolated from fresh faecal samples of Marmota himalayana collected from the Qinghai-Tibetan plateau, China, was determined by using a polyphasic approach. Cells were Gram-reaction-negative, non-sporulating, non-motile, short rods (0.5-1 × 1-2.5 µm). By 16S rRNA gene sequences, the representative strain, HT073016(T), showed highest similarity values with Escherichia fergusonii ATCC 35469(T) at 99.3%, Escherichia coli ATCC 11775(T) at 99.2%, Escherichia albertii LMG 20976(T) at 98.9%, Escherichia hermannii CIP 103176(T) at 98.4%, and Escherichia vulneris ATCC 33821(T) at 97.7%. Phylogenetic analysis based on the 16S rRNA gene sequences showed that the seven strains formed a monophyletic group with five other species of the genus Escherichia. Digital DNA-DNA hybridization studies between strain HT073016(T) and five other species of the genus Escherichia showed that it shared less than 70% DNA-DNA relatedness with all known species of the genus Escherichia, supporting the novel species status of the strain. The DNA G+C content of strain HT073016(T) was 53.8 mol%. On the basis of phenotypic and phylogenetic characteristics, strain HT073016(T) and the six other HT073016(T)-like strains were clearly distinct from the type strains of other recognized species of the genus Escherichia and represent a novel species of the genus Escherichia, for which the name Escherichia marmotae sp. nov. is proposed, with HT073016(T) ( = CGMCC 1.12862(T) = DSM 28771(T)) as the type strain.


Assuntos
Escherichia/classificação , Fezes/microbiologia , Marmota/microbiologia , Filogenia , Animais , Composição de Bases , China , DNA Bacteriano/genética , Escherichia/genética , Escherichia/isolamento & purificação , Ácidos Graxos/química , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
20.
Biomed Mater Eng ; 24(6): 3049-54, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25227013

RESUMO

For improving the detection of micro-calcifications (MCs), this paper proposes an automatic detection of MC system making use of multi-fractal spectrum in digitized mammograms. The approach of automatic detection system is based on the principle that normal tissues possess certain fractal properties which change along with the presence of MCs. In this system, multi-fractal spectrum is applied to reveal such fractal properties. By quantifying the deviations of multi-fractal spectrums between normal tissues and MCs, the system can identify MCs altering the fractal properties and finally locate the position of MCs. The performance of the proposed system is compared with the leading automatic detection systems in a mammographic image database. Experimental results demonstrate that the proposed system is statistically superior to most of the compared systems and delivers a superior performance.


Assuntos
Algoritmos , Inteligência Artificial , Neoplasias da Mama/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Mamografia/métodos , Reconhecimento Automatizado de Padrão/métodos , Lesões Pré-Cancerosas/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Fractais , Humanos , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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