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1.
Int J Mol Sci ; 24(18)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37762356

RESUMO

Esophageal carcinoma is a male-dominant malignancy worldwide, and esophageal adenocarcinoma (EAC) shows more significant sex bias than esophageal squamous cell carcinoma (ESCC) in morbidity and mortality. The G protein-coupled estrogen receptor 1 (GPER1) is involved in several sex-related cancers; however, its expression level in esophageal carcinoma has been poorly investigated and its role is not precisely defined, depending on histological types. In the present study, the mRNA levels of GPER1 in esophageal carcinoma were collected from GEPIA and Oncomine databases for meta-analyses. The protein expression levels of GPER1 were detected by immunohistochemistry in the tissue microarray of EAC and ESCC. The GPER1 selective agonist G1, antagonist G15, and siRNA were applied in vitro to investigate their impacts on esophageal cell lines. Analysis of the RNA levels from the databases showed a decreased expression of GPER1 in overall esophageal carcinoma, and low expression levels of GPER1 were found to be associated with low survival of tumor patients. However, in the subgroup of EAC and its precancerous lesion, Barrett's esophagus, overexpression of GPER1 RNA was increased when compared with the normal tissues. The average staining scores of GPER1 protein in the tissue microarray of EAC were significantly higher than normal esophageal samples, and the rate of positive staining increased with the grade of poor tumor differentiation. The scores of GPER1 protein in ESCC tissues were lower than those in the normal tissues. The results from cell line experiments in vitro showed that the GPER1 agonist G1 inhibited proliferation and promoted apoptosis of ESCC cells EC109 with positive expression of GPER1. G1 had no obvious effect on normal esophageal NE2 cells with weak expression of GPER1. In addition, GPER1 RNA knockdown and application of antagonist G15 reversed the effects of G1 on EC109. The results of this study indicate that the expression levels of GPER1 are higher in EAC than in ESCC, which might be correlated with the dimorphic estrogen signaling pathway in different types of esophageal carcinoma.

2.
PLoS One ; 17(10): e0275854, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36215259

RESUMO

What is the effect of declaring a pandemic? This research assesses behavioral and psychological responses to the WHO declaration of the COVID-19 pandemic, in Hong Kong, Singapore, and the U.S. We surveyed 3,032 members of the general public in these three regions about the preventative actions they were taking and their worries related to COVID-19. The WHO announcement on March 11th, 2020 created a quasi-experimental test of responses immediately before versus after the announcement. The declaration of the pandemic increased worries about the capacity of the local healthcare system in each region, as well as the proportion of people engaging in preventative actions, including actions not recommended by medical professionals. The number of actions taken correlates positively with anxiety and worries. Declaring the COVID-19 crisis as a pandemic had tangible effects-positive (increased community engagement) and negative (increased generalized anxiety)-which manifested differently across regions in line with expectancy disconfirmation theory.


Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , Hong Kong/epidemiologia , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Singapura/epidemiologia
3.
J Colloid Interface Sci ; 616: 921-928, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35259722

RESUMO

Perovskite quantum dots (PQDs) have been widely studied due to the outstanding light emission properties including high quantum efficiency, narrow linewidths and electron transport properties. However, poor stability limits their implication in optical devices, especially working at ambient conditions in the presence of moisture that rapidly attenuate their performance. In this work, PQDs were loaded in nanosized EMT zeolite crystals synthesized from template-free precursor systems resulting in a composite EMT-CsPbBr3. We found and studied for the first time that, in the pores of the zeolites, a small amount of water molecules can promote the crystallization of perovskite nanocrystals. The energy and bond length of perovskite CsPbBr3 confined in the cages of EMT zeolite were calculated in the presence of water molecules, corresponding to the effect of humidity. Crucially, the pore structure of EMT molecular sieve provides an important research model. The great stability and reliability of the EMT-CsPbBr3 as humidity sensor is presented. The luminous intensity efficiency of the EMT-CsPbBr3 composite was maintained at nearly 90% after continuous usage for 6 months. Both the theoretical and experimental results show that a trace amount of water enhances the luminescence of perovskite stabilized in the hydrophilic EMT zeolite.

4.
Gut ; 71(8): 1588-1599, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34930815

RESUMO

OBJECTIVE: Recent studies have provided insights into the gut microbiota in autism spectrum disorder (ASD); however, these studies were restricted owing to limited sampling at the unitary stage of childhood. Herein, we aimed to reveal developmental characteristics of gut microbiota in a large cohort of subjects with ASD combined with interindividual factors impacting gut microbiota. DESIGN: A large cohort of 773 subjects with ASD (aged 16 months to 19 years), 429 neurotypical (NT) development subjects (aged 11 months to 15 years) were emolyed to determine the dynamics change of gut microbiota across different ages using 16S rRNA sequencing. RESULT: In subjects with ASD, we observed a distinct but progressive deviation in the development of gut microbiota characterised by persistently decreased alpha diversity, early unsustainable immature microbiota, altered aboudance of 20 operational taxonomic units (OTUs), decreased taxon detection rate and 325 deregulated microbial metabolic functions with age-dependent patterns. We further revealed microbial relationships that have changed extensively in ASD before 3 years of age, which were associated with the severity of behaviour, sleep and GI symptoms in the ASD group. This analysis demonstrated that a signature of the combination of 2 OTUs, Veillonella and Enterobacteriaceae, and 17 microbial metabolic functions efficiently discriminated ASD from NT subjects in both the discovery (area under the curve (AUC)=0.86), and validation 1 (AUC=0.78), 2 (AUC=0.82) and 3 (AUC=0.67) sets. CONCLUSION: Our large cohort combined with clinical symptom analysis highlights the key regulator of gut microbiota in the pathogenesis of ASD and emphasises the importance of monitoring and targeting the gut microbiome in future clinical applications of ASD.


Assuntos
Transtorno do Espectro Autista , Microbioma Gastrointestinal , Microbiota , Transtorno do Espectro Autista/metabolismo , Criança , Estudos de Coortes , Microbioma Gastrointestinal/genética , Humanos , RNA Ribossômico 16S/genética
5.
Sci Total Environ ; 816: 151652, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-34780835

RESUMO

Glacier collapse is a fairly new type of glacier-related disasters on the Asian Water Towers (AWTs) in the warming climate. On 16 October and 29 October 2018, two glacier collapses occurred in the Sedongpu Basin, 7 km downstream from Gyala Village, Paizhen Town, Miling County, on the Yarlung Tsangpo River (YTR). The ice and entrained debris flows caused by the glacier collapses blocked the YTR, resulting in a potential threat to residents and transport lines upstream and downstream. Through post-event field investigations with a helicopter and an unmanned aerial vehicle (UAV), remote sensing interpretation, and seismic, hydrological, and meteorological observations, the process and potential mechanisms of the glacier collapse-induced river blocking (GCRB) disasters were investigated. We confirmed that the first glacier collapse event occurred at 22:48 (Beijing time) on 16 October 2018 and the second began at 08:03 on 29 October 2018. Approximately 130 × 106 m3 of ice and debris detached from the glacier during the glacier collapse, and we calculated that the river blocking fans caused by the first and second glacier collapse event covered ~1.36 km2 and ~ 1.29 km2 on the main watercourse of the YTR, respectively. We determined that the GCRB incidents represent a disaster chain of glacier collapse → glacial debris flow → river blockage → dammed lake → outburst flood. These incidents arise due to a combination of factors, including glacier activity, climate warming, heavy precipitation, pre-seismic activity, and high topographic relief. In the context of climate warming on the Tibetan Plateau, such glacier collapse induced disaster chains will continue or even intensify in the future. To protect against glacier collapse disasters in the Grand Canyon on the YTR, we established a monitoring and early warning system (EWS), which has already successfully sounded alerts for GCRB incidents. As a major element of an integrated risk management strategy, the EWS represents a viable and promising tool for mitigating climate change-related risks.


Assuntos
Camada de Gelo , Rios , Inundações , Lagos , Tibet
6.
PLoS One ; 16(9): e0256939, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34478454

RESUMO

Social role disruption is a state involving upheaval of social identities, routines and responsibilities. Such disruption is presently occurring at a global scale due to the COVID-19 pandemic, which poses a threat not only to health and security but also to the social roles that underlie people's daily lives. Our collective response to combat the virus entails, for example, parents homeschooling children, friends socializing online, and employees working from home. While these collective efforts serve the greater good, people's social roles now lack continuity from what was authentic to the roles before the pandemic began. This, we argue, takes a psychological toll. Individuals feel inauthentic, or alienated and out-of-touch from their "true" selves, to the extent their social roles undergo change. As evidence, we report survey (Studies 1 & 4) and experimental (Studies 2 & 3) evidence that COVID-19-related role changes indeed increase inauthenticity. This effect occurs independent of (a) how positively/negatively people feel about COVID-19 (Study 2) and (b) how positively/negatively people feel about the role change itself (Studies 3 & 4). Moreover, we identify two moderators of this effect. First, this effect occurs when (and ostensibly because) the social roles undergoing change are central to an individual's sense of self (Study 2). Second, this effect depends on an individual's temporal perspective. People can safeguard their self-authenticity in the face of changing social roles if they stay focused on the here-and-now (the present and immediate future), rather than focusing on the past (pre-COVID-19) or future (post-COVID-19) (Studies 3 & 4). This advantage for present-focused coping is observed in both the U.S.A. (Study 3) and Hong Kong (Study 4). We suggest that the reason people feel more authentically themselves when they maintain a present focus is because doing so makes the discontinuity of their social roles less salient.


Assuntos
COVID-19/epidemiologia , COVID-19/psicologia , Pandemias , SARS-CoV-2/isolamento & purificação , Adaptação Psicológica , Adolescente , Adulto , COVID-19/virologia , Criança , Emoções , Feminino , Hong Kong , Humanos , Masculino , Personalidade/fisiologia , SARS-CoV-2/patogenicidade , Inquéritos e Questionários , Adulto Jovem
7.
Zhen Ci Yan Jiu ; 45(11): 888-94, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33269832

RESUMO

OBJECTIVE: To explore the protective effect of electroacupuncture (EA) on hepatic ischemia-reperfusion injury (HIRI) and the expression of high mobility group protein 1 (HMGB1) in liver tissues in rats. METHODS: A total of 40 male SD rats were randomly divided into 4 groups, namely sham control, HIRI model, "Ganshu"(BL18) -"Yanglingquan"(GB34) and non-acupoint group, with 10 rats in each group. The HIRI model was induced by blocking the arteries, veins and bile ducts supplying the middle and left lobes of the liver for 1 h, and reperfusion for 4 h to induce an area of about 70% HIRI. EA was applied to bila-teral BL18 and GB34, or non-acupoints about 6-8 mm to the bilateral BL18 for 30 min before modeling. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were measured by using an automatic biochemical analyzer. Serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and HMGB1 levels were assayed by ELISA. Hematoxylin - eosin (H.E.) staining was used to observe histopathological changes of the liver tissue by using tissue injury scaling (0-3 scores). The expression of HMGB1 protein in liver tissues was detected by immunohistochemical staining, Western blot and PCR, separately. RESULTS: Following modeling and compared with the sham group, the levels of serum ALT, AST, TNF-α, IL-6, and HMGB1 contents, the number of HMGB1 immunoreaction (IR)-positive cells, and HMGB1 protein and mRNA were significantly increased (P<0.01). After the treatment, the contents of serum ALT, AST, TNF-α, IL-6, and HMGB1, liver HMGB1 IR-positive cells, protein and mRNA were considerably down-regulated in the BL18-GB34 group (P<0.05), rather than in the non-acupoint group (P>0.05) in contrast to the model group. H.E. stain showed a higher liver injury score in the model group than in the sham group (P<0.01), and a lower liver injury score in the BL18-GB34 group (not the non-acupoint group) relevant to the model group (P<0.05). CONCLUSION: EA of BL18 and GB34 points has a protective effect on ischemic liver injury in rats with HIRI, which may be associated with its functions in inhibiting the migration and release of HMGB1 from the nucleus to the cytoplasm and in down-regulating the expression of inflammatory factors.


Assuntos
Eletroacupuntura , Proteína HMGB1 , Traumatismo por Reperfusão , Animais , Proteína HMGB1/genética , Fígado , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/terapia
8.
J Mater Chem B ; 7(38): 5797-5807, 2019 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-31483422

RESUMO

Photodynamic therapy (PDT), as an essential tumor treatment method, has received great attention; however, there are still some challenges such as hydrophobicity of most of the photosensitizers, safety of in vivo transport, and characteristics of oxygen consumption. Herein, we used albumin as the nanocarrier for the loading of Chlorin e6 (Ce6) photosensitizer. In the meantime, tirapazaming (TPZ) was co-loaded onto the nanocomposite, which could be activated by hypoxia caused by PDT for enhanced therapy. Considering the over irradiation problem, a strategy for measuring PDT degree by ratio fluorescence was utilized. The PDT monitoring design relies on ratio emissions of C6 (Coumarin 6) and Ce6 molecules since the red emission of Ce6 is dependent on the PDT capability. Based on the characterization of the albumin nanocomposites, we further explored the combined therapy effect at both the in vitro and in vivo levels and attained the corresponding results.


Assuntos
Cumarínicos/química , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Soroalbumina Bovina/química , Tiazóis/química , Tirapazamina/química , Animais , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofilídeos , Humanos , Luz , Fígado/patologia , Camundongos , Microscopia Confocal , Nanopartículas/toxicidade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Transplante Homólogo
9.
Sci Total Environ ; 686: 1030-1038, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31200301

RESUMO

Black carbon (BC), which consists of the strongest light-absorbing particles (LAP) in snow/ice, has been regarded as a potential factor accelerating the melting of glaciers and snow cover over the Third Pole. During the winter and summer of 2016, snow, ice and topsoil were sampled from the Laohugou basin located on the northeastern Tibetan Plateau. Concentrations of BC in Laohugou Glacier No. 12 (LG12) and snow cover in this basin (LSC) varied broadly (21.7-2700.1 and 89.6 to 6326.2 ng g-1, respectively), indicating large spatiotemporal variability in wet, dry and post depositional conditions. Further, internally mixed BC in snow grains enhanced the albedo reduction (15.0-26.3%) more than externally mixed BC in LG12 and LSC. Dust played a more important role than BC in accelerating the melting of LG12, whereas these components played comparable roles in accelerating the melting of LSC. In total, externally mixed BC and dust reduced the albedo by 0.075-0.423, with an associated mean radiative forcing (RF) of 97.5 ±â€¯41.5 Wm-2 in LSC. This level was lower than those in the ablation zone (354.1 ±â€¯81.2 Wm-2) and accumulation zone (145.6 ±â€¯76.7 Wm-2) of LG12 because of discrepancies in LAP concentrations, solar zenith angles and incoming shortwave radiation. Furthermore, we observed that topsoil containing abundant BC was transported along the slope from the debris to the LG12 surface ice, and topsoil in this region could be lifted by strong mountain-valley winds and then deposited on snow/ice surfaces, which affected the LAP concentrations. Therefore, this study is important for understanding the role of BC and dust in the melting of snow/ice in the northeastern Tibetan Plateau.

10.
Sci Rep ; 8(1): 17291, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30470822

RESUMO

The discharge of one of the world's largest river - Indus River was reported to be increasing that was not supported by the Karakoram (KK) glacier expansion. A major hydrometric bias was ignored, which seemed similar to the montage that the Himalayan glaciers would disappear. This study proposed a framework for quantifying the bias resulting from inaccurate data affecting hydrologic studies on the Indus. We constructed a statistical model by converting the rating curves of rivers into air temperature (T) - discharge (Q) curves from an adjacent catchment in China where flow measurement was carried out using a standard method. We found that most flow data for the Indus were much greater than the error limits of T-Q curves estimated by daily data, a greater bias occurred in recent decades when discharge increased, the higher the flow was, the larger the bias was. The estimated mean annual and maximum monthly bias was 22.5% and 210%, respectively. These biases indicated that discharge increase in the Indus probably resulted from the large errors of hydrometrics without a scientific basis. We suggested a montage bias was needed in the hydrologic science of KK's rivers that may strongly affect water resource management.

11.
Nanotechnology ; 29(28): 285706, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-29693553

RESUMO

Inorganic perovskite quantum dots (QDs) have attracted wide attention in display and solid-state lighting because of their easily tunable band-gaps and high photoluminescence quantum yields (PLQY) of green light emission. However, some drawbacks limit their practical applications, including the low PLQY of blue light emission and the instability in the moisture environment. In this work, efficient blue-light emitting CsPbBr3 perovskite QDs with PLQY of 72% were developed through a bandgap engineering approach. The achieved blue-light emitting PLQY is much higher than the values acquired in the inorganic perovskite QDs in the literature. And the emission color of the as-prepared QDs can be facially tuned by only adjusting the reaction temperature. Further, the mono-dispersed perovskite QDs@SiO2 composites were constructed benefiting from the low temperature synthesis. The optical performance of the QDs could be well persisted even in the moisture environment. Finally, the as-prepared QDs@SiO2 composite was fabricated as the QD ink on the anti-counterfeit printing technology, from which the obtained pattern would emit varied color under UV lamp. And the as-prepared composites was also applied for fabricating WLED, with Commission Internationale de l'Eclairage (CIE) color coordinates of (0.33, 0.38) and power efficiency of 32.5 lm W-1, demonstrating their promising potentials in solid-state lighting.

12.
Asia Pac J Clin Oncol ; 14(3): 167-178, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28670694

RESUMO

AIM: We aimed to assess economic burden of breast cancer (BC) diagnosis and treatment in China through a multicenter cross-sectional study, and to obtain theoretical evidence for policy-making. METHODS: This survey was conducted in 37 hospital centers across 13 provinces in China from September 2012 to December 2014. We collected information on the subject characteristics. We then assessed the medical and non-medical expenditure for BC diagnosis and treatment, factors influencing the average case expense, variations between medical and non-medical expenditure at different clinical stages, economic impact of overall expenditure in newly diagnosed course after reimbursement to the patient's family, composition of non-medical expenditure and time loss for the patient and family. RESULTS: Among 2746 women with BC (72.6% were admitted to specialized hospitals), the overall average expenditure was US $8450 (medical expenditure: $7527; non-medical expenditure: $922). Significant differences were found among the overall expenditure in the four clinical stages (P < 0.0001); the expenditure was higher in stages III and IV than that in stages I and II, whereas the stage IV was the highest (P < 0.0001). Moreover, a higher self-reported predicted reimbursement ratio was associated with a less economic impact on the patient's family, and the average time lost was estimated as $1529. CONCLUSIONS: Early detection and treatment of breast cancer might be effective for decreasing the economic burden, because costs escalate as the degree of malignancy increases.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/economia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , China , Custos e Análise de Custo , Estudos Transversais , Feminino , Gastos em Saúde , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
13.
Biochem Biophys Res Commun ; 485(3): 577-583, 2017 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-27923659

RESUMO

Radiation pulmonary injury is related to the accumulation of extracellular matrix proteins in the alveolar interstitial space. Matrilin-2 as a component of extracellular filamentous networks, present higher level in the lung tissue from irradiated mice and irradiated pulmonary epithelial cell line, HPAEpiC cells. Knockdown of endogenous matrilin-2 prevents the apoptosis of HPAEpiC cell induced by the irradiation injury. Consistently, over-expression of matrilin-2 reduced the proliferation and induced apoptosis of HPAEpiC cells. Matrilin-2 promotes the expression of p21 via increasing the transcriptional activity of p53, by which induces the G1 phase arresting in HPAEpiC cells. In summary, matrilin-2, increased by irradiation, reduced the proliferation and induces apoptosis of pulmonary epithelial cells via p53/p21 pathway.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Células Epiteliais/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Proteínas Matrilinas/genética , Animais , Apoptose/efeitos da radiação , Western Blotting , Proliferação de Células/efeitos da radiação , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células Epiteliais/efeitos da radiação , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos da radiação , Expressão Gênica/efeitos da radiação , Humanos , Pulmão/metabolismo , Pulmão/efeitos da radiação , Masculino , Proteínas Matrilinas/metabolismo , Camundongos Endogâmicos C57BL , Alvéolos Pulmonares/citologia , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
14.
ANZ J Surg ; 87(12): E251-E255, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27226356

RESUMO

BACKGROUND: NDUFA4L2 (NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2, also called NADH-ubiquinone oxidoreductase MLRQ subunit homologue) was clearly enriched in the mitochondrial fraction under hypoxic conditions, and immunofluorescence showed a clear colocalization of NDUFA4L2 and cytochrome c in some tumour cells. However, little study has investigated its prognostic value in colorectal cancer (CRC). METHODS: In our study, mRNA-NDUFA4L2 and protein expression were analysed in 150 cases of CRC and adjacent normal tissues using immunohistochemistry, semi-quantitative reverse transcriptase-polymerase chain reaction. The correlation between NDUFA4L2 expression and clinicopathological factors was evaluated by the Chi-square test. Overall survival of patients was analysed by the Kaplan-Meier method. RESULTS: NDUFA4L2 overexpression was observed in 84% (126/150) of CRC tissues, but only in 24.7% (37/150) of adjacent normal tissues (P < 0.05). Semi-quantitative reverse transcriptase-polymerase chain reaction showed average mRNA expression levels to be 23.34 ± 1.356 and 4.34 ± 1.132 for CRC tissue and adjacent normal tissue (P < 0.05). Statistical analysis showed a significant correlation of NDUFA4L2 expression with histological grade, Dukes' stages, lymph node metastasis and liver metastasis. More importantly, multivariate analysis indicated that overexpression of NDUFA4L2 was an independent prognostic factor for CRC patients (P = 0.002). NDUFA4L2-negative patients had a higher tumour-free/overall survival rate than patients with high NDUFA4L2 expression (P = 0.001 and 0.002, respectively). CONCLUSIONS: Our data suggest that NDUFA4L2 overexpression is associated with tumour progression and a poor prognosis in CRC patients.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Complexo I de Transporte de Elétrons/metabolismo , Neoplasias Hepáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Complexo I de Transporte de Elétrons/genética , Feminino , Humanos , Imuno-Histoquímica/métodos , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética
15.
Int J Mol Med ; 38(4): 1208-16, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27513632

RESUMO

MicroRNA (miR)-221 plays an essential role in the epithelial-mesenchymal transition (EMT). High mobility group AT-hook 2 (HMGA2), is a key regulator of EMT. However, the role of miR­221 in pulmonary fibrosis, and the association between miR­221 and HMGA2 remain largely unknown. For this purpose, we examined the expression of miR­221 and HMGA2 in human idiopathic pulmonary fibrosis (IPF) tissues and pulmonary cells, namely the adenocarcinoma A549 and human bronchial epithelium (HBE) cell lines, and found that the expression of miR­221 was inhibited in both tissues and cells whereas high mRNA and protein expression of HMGA2 was observed. Additionally, transforming growth factor­ß1 (TGF­ß1) induced the EMT, characterized by the upregulated expression of the mesenchymal markers, namely N­cadherin, vimentin, α­smooth muscle actin, collagen I and collagen III, and the downregulated expression of the epithelial marker E-cadherin in A549 and HBE cells. We then performed transfection with miR­221 mimics, and found that the expression of phosphorylated-Smad3 in miR­221­overexpressing cells was significantly downregulated, compared with that in the TGF­ß1-treated cells without transfection. Furthermore, the overexpression of miR­221 decreased the expression of HMGA2, suppressed the EMT, and inhibited the proliferation of A549 and HBE cells. HMGA2 was directly targeted by miR­221 which was confirmed by the dual-luciferase reporter gene assay. Finally, a mouse model of bleomycin (BLM)­induced pulmonary fibrosis was used to confirm the effect of miR­221 on EMT. Hematoxylin and eosin staining showed that BLM induced thicker alveolar walls and more collagen deposition, whereas miR­221 treatment reduced lung fibrosis and the tissues exhibited thinner alveolar walls and normal lung alveoli. Furthermore, the EMT process was suppressed following miR­221 injection. Taken together, these findings sugest that miR­221 targets HMGA2 to inhibit BLM­induced pulmonary fibrosis through the TGF­ß1/Smad3 signaling pathway.


Assuntos
Transição Epitelial-Mesenquimal/genética , Proteína HMGA2/genética , Fibrose Pulmonar Idiopática/genética , MicroRNAs/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células A549 , Animais , Bleomicina , Brônquios/patologia , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Proteína HMGA2/metabolismo , Humanos , Fibrose Pulmonar Idiopática/patologia , Camundongos , MicroRNAs/genética , Transdução de Sinais/genética , Regulação para Cima/genética
16.
Oncotarget ; 7(22): 33472-82, 2016 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-26985769

RESUMO

Cancer immunotherapy has primarily been focused on attacking tumor cells. However, given the close interaction between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), CAF-targeted strategies could also contribute to an integrated cancer immunotherapy. Fibroblast activation protein α (FAP α) is not detectible in normal tissues, but is overexpressed by CAFs and is the predominant component of the stroma in most types of cancer. FAP α has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. When all FAP α-expressing cells (stromal and cancerous) are destroyed, tumors rapidly die. Furthermore, a FAP α antibody, FAP α vaccine, and modified vaccine all inhibit tumor growth and prolong survival in mouse models, suggesting FAP α is an adaptive tumor-associated antigen. This review highlights the role of FAP α in tumor development, explores the relationship between FAP α and immune suppression in the TME, and discusses FAP α as a potential immunotherapeutic target.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Fibroblastos Associados a Câncer/efeitos dos fármacos , Gelatinases/antagonistas & inibidores , Imunoterapia/métodos , Proteínas de Membrana/antagonistas & inibidores , Neoplasias/terapia , Animais , Fibroblastos Associados a Câncer/enzimologia , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/patologia , Morte Celular/efeitos dos fármacos , Endopeptidases , Gelatinases/imunologia , Gelatinases/metabolismo , Humanos , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Terapia de Alvo Molecular , Neoplasias/enzimologia , Neoplasias/imunologia , Neoplasias/patologia , Serina Endopeptidases/imunologia , Serina Endopeptidases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Evasão Tumoral , Microambiente Tumoral
17.
J Ovarian Res ; 8: 78, 2015 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-26589590

RESUMO

BACKGROUND: galectin-1 has been implicated in tumor invasion and metastasis and is frequently over-expressed in epithelial ovarian cancer (EOC), but its potential as a biomarker remains unclear. In this novel study, we have explored the possible use of galectin-1 as a biomarker for EOC. METHODS: galectin-1 in sera was evaluated by ELISA in a pilot panel of EOC patients, healthy volunteers, patients with benign gynecologic tumors or other gynecologic malignancies. We examined galectin-1 expression in EOC tumor samples by Western Blot, qRT-PCR and immunohistochemistry. In vitro experiments were conducted to elucidate the biologic role of galectin-1 in EOC progression using over-expression of galectin-1 in OVCAR-3 cells. We also looked for the association of galectin-1 expression with clinic pathological variables and survival outcomes in EOC. RESULTS: A significant difference was detected in serum galectin-1 between EOC patients with non-metastatic and those with metastatic disease, but not between EOC patients and healthy volunteers. It increased in recurrent cases and decreased after debulking surgery. Both of galectin-1 mRNA and protein levels were increased in 90 % of the examined EOC tissue samples, compared with a wedge resection of a normal ovary. High galectin-1 in peritumor stroma was primarily detected in advanced stages of EOC. Over expression of galectin-1 significantly increased the ability of OVCAR-3 cells' migration and invasion. CONCLUSIONS: Our results suggest that galectin-1 might play a role in tumor progression and be associated with poor outcome in EOC. It could be a novel prognostic and progression biomarker in EOC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Galectina 1/metabolismo , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Ovarianas/diagnóstico , Adulto , Idoso , Antígeno Ca-125/metabolismo , Carcinoma Epitelial do Ovário , Estudos de Casos e Controles , Movimento Celular/fisiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Prognóstico , Células Estromais/metabolismo , Células Tumorais Cultivadas , Adulto Jovem
18.
Int J Mol Med ; 36(6): 1648-56, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26499313

RESUMO

Mutations in matrilin-3 are associated with common skeletal diseases, such as hand osteoarthritis (HOA), as well as rare chondrodysplasias, such as multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). In the present study, we constructed the mutations R116W [at the von Willebrand factor, type A (vWFA) domain], T298M [at the first epidermal growth factor (EGF) domain] and C299S (at the first EGF domain), according to the mouse sequence, which are associated with human MED, HOA and SEMD, respectively, by overlap extension PCR and inserted them into an expression vector (pcDNA3.1/v5-His). We transfected these contructs into the COS-1 or MCT cells, and the results revealed that the HOA-related matrilin-3 mutation (T298M) leads to a high expression level of growth arrest DNA damage-inducible gene 153 (GADD153, also known as CHOP; an endoplasmic reticulum stress marker), as shown by western blot analysis and does not significantly affect protein secretion, as shown by immunofluorescence staining; however, osteochondroplasia, i.e., MED-related (R116W) and SEMD-related (C299S) mutations lead to both high levels of GADD153 expression and protein trafficking into the cytoplasm and form multiple vacuoles in cells, which in turn leads to insufficient protein secretion.


Assuntos
Estresse do Retículo Endoplasmático/genética , Proteínas Matrilinas/genética , Proteínas Mutantes/genética , Mutação , Animais , Sítios de Ligação/genética , Western Blotting , Células COS , Células Cultivadas , Chlorocebus aethiops , Condrócitos/citologia , Condrócitos/metabolismo , Condrócitos/ultraestrutura , Cobaias , Humanos , Articulação do Joelho/metabolismo , Proteínas Matrilinas/metabolismo , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Proteínas Mutantes/metabolismo , Osteoartrite/genética , Osteocondrodisplasias/genética , Transporte Proteico , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Transfecção
19.
J Altern Complement Med ; 21(11): 667-72, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26331434

RESUMO

OBJECTIVE: Postoperative pain is caused by surgical injury and trauma; is stressful to patients; and includes a series of physiologic, psychological, and behavioral reactions. Effective postoperative analgesia helps improve postoperative pain, perioperative safety, and hospital discharge rates. This study aimed to observe the influence of postoperative intravenous sufentanil patient-controlled analgesia combined with music therapy versus sufentanil alone on hemodynamics and analgesia in patients with lung cancer. METHODS: This was a randomized parallel study performed in 60 patients in American Society of Anesthesiologists class I or II undergoing lung cancer resection at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University. Patients were randomly assigned to a music therapy (MT) group and a control (C) group. The MT group underwent preoperative and postoperative music intervention while the C group did not. Both groups received intravenous patient-controlled sufentanil analgesia. The primary outcome was the visual analogue scale (VAS) score at 24 hours after surgery. The secondary outcomes included hemodynamic changes (systolic blood pressure, diastolic blood pressure, heart rate), changes on the Self-Rating Anxiety Scale (SAS), total consumption of sufentanil, number of uses, sedation, and adverse effects. The postoperative sufentanil dose and analgesia frequency were recorded. RESULTS: Compared with the C group, the MT group had significantly lower VAS score, systolic and diastolic blood pressure, heart rate, and SAS score within 24 hours after surgery (p < 0.01). In addition, postoperative analgesia frequency and sufentanil dose were reduced in the MT group (p < 0.01). CONCLUSIONS: Combined music therapy and sufentanil improves intravenous patient-controlled analgesia effects compared with sufentanil alone after lung cancer surgery. Lower doses of sufentanil could be administered to more effectively improve patients' cardiovascular parameters.


Assuntos
Neoplasias Pulmonares/cirurgia , Musicoterapia/estatística & dados numéricos , Dor Pós-Operatória/terapia , Sufentanil/administração & dosagem , Sufentanil/uso terapêutico , Adulto , Idoso , Pressão Sanguínea/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade
20.
Technol Health Care ; 23 Suppl 1: S119-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26410313

RESUMO

BACKGROUND: TGFß 1 is very important in the synthesis and degradation of extracellular matrix (ECM), and also in the mediation of human pulmonary fibroblasts proliferation, and miR-29 plays an important role in this process. OBJECTIVE: In the present study, the effects of TGFß 1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFß 1 were examined in human pulmonary fibroblasts. METHODS AND RESULTS: Treatment of the human IMR-90 cells with TGFß 1 caused a decrease in the expression of miR-29a/b/c as determined by real-time PCR analysis. TGFß 1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFß 1-induced phenotype changes in IMR-90. Western blot analyses showed that TGFß 1 treatment unchanged total protein expression levels of ß -catenin, but phosphorylation of ß -catenin and the expression levels of wnt3a and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked DKK1, wnt3a, and phosphorylation of ß -catenin and decreased expression of COL1A1 after TGFß 1 treatment. Our results showed that TGFß 1 activated the wnt/ß -catenin pathway, and this activation was essential for the expression of miR-29 in IMR-90. CONCLUSIONS: The results indicate a novel biological function of the wnt/ß -catenin pathway in IMR-90. Elevated expression of miR-29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human IMR-90.


Assuntos
Matriz Extracelular/metabolismo , MicroRNAs/biossíntese , Fator de Crescimento Transformador beta1/farmacologia , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo , Linhagem Celular , Proliferação de Células , Colágeno Tipo I/biossíntese , Cadeia alfa 1 do Colágeno Tipo I , Fibroblastos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Pulmão , Regulação para Cima
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