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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 303: 123178, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37499473

RESUMO

Abiotic stress and oxidative stress are closely related to the health status of plants. Plants will produce oxidative stress under abiotic stress, induce mitochondrial dysfunction, cause programmed cell death, and decrease plant survival rate. It is well known that rice is an essential crop for humans, but its cadmium tolerance is poor. Therefore, it is crucial to determine whether cadmium stress causes oxidative stress in rice in order to guide rice cultivation. Hydrogen peroxide (H2O2), a highly reactive oxygen species (ROS), is one of the most critical signals in corps under oxidative stress. In this work, we adopted a near-infrared (NIR) H2O2 fluorescent probe YFE-1 and a cadmium ion (Cd2+) fluorescent probe SCP to observe the fluctuation of H2O2 in rice roots under Cd2+ co-incubation conditions. Due to the advantages of fast response (within 2 min), a large Stokes shift (181 nm), good selectivity, and a low detection limit (LOD:26.4 nM), YFE-1 achieved the visualization of H2O2 produced by Cd2+ stress in rice roots. This study provides a new idea for assessing the risk of oxidative stress of Cd2+ in rice roots. It is expected to guide the control of Cd2+ in the rice planting industry to improve rice yield.


Assuntos
Cádmio , Oryza , Humanos , Cádmio/metabolismo , Peróxido de Hidrogênio/metabolismo , Oryza/metabolismo , Corantes Fluorescentes/metabolismo , Fluorescência , Estresse Oxidativo , Antioxidantes/metabolismo , Plantas/metabolismo , Raízes de Plantas/metabolismo
2.
Tissue Eng Regen Med ; 20(3): 447-459, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36947320

RESUMO

BACKGROUND: Human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising therapy for immune and inflammatory diseases. However, how to maintain the activity and unique properties during cold storage and transportation is one of the key factors affecting the therapeutic efficiency of hUCMSCs. Schisandrin B (SchB) has many functions in cell protection as a natural medicine. In this study, we investigated the protective effects of SchB on the hypothermic preservation of hUCMSCs. METHODS: hUCMSCs were isolated from Wharton's jelly. Subsequently, hUCMSCs were exposed to cold storage (4 °C) and 24-h re-warming. After that, cells viability, surface markers, immunomodulatory effects, reactive oxygen species (ROS), mitochondrial integrity, apoptosis-related and antioxidant proteins expression level were evaluated. RESULTS: SchB significantly alleviated the cells injury and maintained unique properties such as differentiation potential, level of surface markers and immunomodulatory effects of hUCMSCs. The protective effects of SchB on hUCMSCs after hypothermic storage seemed associated with its inhibition of apoptosis and the anti-oxidative stress effect mediated by nuclear factor erythroid 2-related factor 2 signaling. CONCLUSION: These results demonstrate SchB could be used as an agent for hypothermic preservation of hUCMSCs.


Assuntos
Lignanas , Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Lignanas/farmacologia , Lignanas/metabolismo , Cordão Umbilical
3.
Forensic Sci Int ; 342: 111505, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36493654

RESUMO

In order to investigate the sensitivity of parameters and analyze the uncertainty of reconstructed results in traffic accident, the impact of correlations between parameters on accident reconstruction results was taken into account using uncertainty analysis. Based on unscented transformation (UT), a parameter sensitivity analysis method and an efficient uncertainty analysis method in accident reconstruction were proposed. Sensitivity analysis was performed through the sigma point sets generated by the UT method. A first-order response surface model was constructed to analyze the sensitivity of accident reconstruction parameters combined with regression analysis, which is more flexible and controllable than the general experimental design. For the uncertainty analysis of the reconstructed results, the other methods have been used to demonstrate the validity of the proposed method, including the first second-order method of moments (FOSM), the uncertainty theory, and the Monte Carlo (MC) methods, through analyzing the numerical and real-world cases. The results show that the presented method has high accuracy, significantly reduces the computational burden, and does not depend on the distribution type of variables. When considering the effect of the correlation between parameters of the vehicle-pedestrian crash on accident reconstruction results, the results show that the correlation coefficient between random variables had a much more significant impact on the standard deviation of vehicle speed than on the mean value of vehicle speed. Regardless of negative or positive correlations, the relative error of standard deviation of vehicle speed increased continuously as the correlation increased, reaching 52%. The proposed method is effective and reliable for vehicle collision accident reconstruction under uncertainty and correlation, which can provide more comprehensive information in accident reconstruction.


Assuntos
Pedestres , Humanos , Incerteza , Acidentes de Trânsito , Método de Monte Carlo
4.
Appl Physiol Nutr Metab ; 47(9): 949-962, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35728265

RESUMO

This study examined the alterations of heart rate variability (HRV) following iso-duration resistance (RES) and sprint-interval exercises (SIE) by comparing with that of non-exercise control (CON) in 14 non-obese (NOB) and 15 obese (OB) young men. Time and frequency domain measures as well as nonlinear metrics of HRV were assessed before and immediately after exercise, and during every 20 min until 120 min post-exercise. The variables during the first 4 h of actual sleep time at night, and the period of 12-14 h post-exercise were also measured. All trials were scheduled at 20:00. It was found that RES and SIE attenuated the HRV in both NOB and OB (P < 0.05), and the attenuated HRV restored progressively during subsequent recovery. Although the changes in HRV indices among various time points during the recovery period and its interaction across RES, SIE, and CON were not different between NOB and OB, the restoration of the declined HRV indices to corresponding CON level in the 2 exercise trials in OB appeared to be sluggish in relative to NOB. Notwithstanding, post-exercise HRV that recorded during actual sleep at night and during 12-14 h apart from exercise were unvaried among the 3 trials in both groups (P > 0.05). These findings suggest that obesity is likely to be a factor hindering the removal of exercise-induced cardiac autonomic disturbance in young men. Nonetheless, the declined HRV following both the RES and SIE protocols was well restored after a resting period of ∼10 h regardless of obesity. The study was registered at ISRCTN as https://doi.org/10.1186/ISRCTN88544091.


Assuntos
Sistema Nervoso Autônomo , Exercício Físico , Sistema Nervoso Autônomo/fisiologia , Exercício Físico/fisiologia , Coração/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Obesidade/terapia
5.
Front Oncol ; 12: 1030080, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36591477

RESUMO

Introduction: Central pancreatectomy (CP) is a standard surgical procedure for benign and low-grade malignant pancreatic neoplasms in the body and neck of the pancreas. Higher incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) after CP than after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) has been reported, but no nomogram for prediction of CR-POPF after open CP has been previously established. Methods: Patients undergoing open CP for benign or low-grade malignant pancreatic neoplasms in the department of Hepatobiliary and Pancreatic (HBP) surgery of Shanghai Changhai Hospital affiliated to Naval Medical University between January 01, 2009 and December 31,2020 were enrolled. Pre-, intra- and post-operative parameters were analyzed retrospectively. Results: A total of 194 patients, including 60 men and 134 women, were enrolled with median age of 52 years (21~85 years). 84 patients (43.3%) were overweight (BMI>23.0 Kg/m2) and 14 (7.2%) were obese (BMI>28.0 Kg/m2). Pathological diagnoses ranged from serous cystic neoplasm (32.5%), solid pseudopapillary neoplasm (22.2%), pancreatic neuroendocrine tumor (20.1%), intraductal papillary mucinous neoplasm (18.0%) to mucinous cystic neoplasm (5.2%). All patients had soft pancreatic texture. Main pancreatic duct diameters were ≤0.3cm for 158 patients (81.4%) and were ≥0.5cm in only 12 patients (6.2%). A stapler (57.7%) or hand-sewn closure (42.3%) were used to close the pancreatic remnant. The pancreatic anastomosis techniques used were duct to mucosa pancreaticojejunostomy (PJ)-interrupted suture (47.4%), duct to mucosa PJ-continuous suture (43.3%), duct to mucosa "HO" half-purse binding PJ (5.2%) and invaginating pancreaticogastrostomy (4.1%). Post-surgical incidences of CR-POPF of 45.9%, surgical site infection of 28.9%, postpancreatectomy hemorrhage of 7.7% and delayed gastric emptying of 2.1% were found. Obesity and pancreatic anastomosis technique were independent risk factors of CR-POPF, with a concordance index of 0.675 and an Area Under the Curve of 0.678. Discussion: This novel nomogram constructed according to obesity and pancreatic anastomosis technique showed moderate predictive performance of CR-POPF after open CP.

6.
Chin Clin Oncol ; 9(4): 54, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32576018

RESUMO

BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS) has been adopted by some surgeons in the treatment of left-sided pancreatic cancer (PDAC). Low disease incidence and heterogenous disease biology make robust prospective comparison of RAMPS and standard distal pancreatosplenectomy (DPS) difficult. METHODS: Consecutive cases of chemo-naïve patients undergoing open RAMPS and DPS for PDAC between 2010-2017 at two international high-volume pancreatectomy centers were compared. Cox proportional hazard modeling was utilized for multivariate analysis. RESULTS: We identified 193 DPS and 253 RAMPS during the study period. DPS was associated with higher rates of median estimated blood loss (500 vs. 300 cc, P<0.001), median total harvested lymph nodes (18 vs. 12, P<0.001) and R0 resection (94.3% vs. 88.9%, P=0.013). There were no differences in rates of postoperative pancreatic fistula (16.5% vs. 17.8%, P=1) or postoperative hemorrhage (5.9% vs. 3.6%, P=0.385) (DPS vs. RAMPS). After controlling for significant clinical pathological parameters, RAMPS was associated with non-superior recurrence-free survival (RFS) (HR 0.29; 95% CI, 0.07-1.27, P=0.101) and overall-survival (HR 1.03; 95% CI, 0.71-1.49, P=0.895) compared with DPS. Similar results were observed in node-positive patients. CONCLUSIONS: RAMPS is safe and effective in the treatment of PDAC, but is not associated with an improvement in either RFS or overall-survival over DPS.


Assuntos
Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Esplenectomia/métodos , Idoso , Feminino , Humanos , Masculino , Neoplasias Pancreáticas
7.
Proc Natl Acad Sci U S A ; 114(3): 435-442, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28096504

RESUMO

China's 13th Five-Year Plan, launched in March 2016, provides a sound policy platform for the protection of marine ecosystems and the restoration of capture fisheries within China's exclusive economic zone. What distinguishes China among many other countries striving for marine fisheries reform is its size-accounting for almost one-fifth of global catch volume-and the unique cultural context of its economic and resource management. In this paper, we trace the history of Chinese government priorities, policies, and outcomes related to marine fisheries since the 1978 Economic Reform, and examine how the current leadership's agenda for "ecological civilization" could successfully transform marine resource management in the coming years. We show how China, like many other countries, has experienced a decline in the average trophic level of its capture fisheries during the past few decades, and how its policy design, implementation, and enforcement have influenced the status of its wild fish stocks. To reverse the trend in declining fish stocks, the government is introducing a series of new programs for sustainable fisheries and aquaculture, with greater traceability and accountability in marine resource management and area controls on coastal development. As impressive as these new plans are on paper, we conclude that serious institutional reforms will be needed to achieve a true paradigm shift in marine fisheries management in China. In particular, we recommend new institutions for science-based fisheries management, secure fishing access, policy consistency across provinces, educational programs for fisheries managers, and increasing public access to scientific data.


Assuntos
Pesqueiros , Animais , China , Conservação dos Recursos Naturais/economia , Conservação dos Recursos Naturais/legislação & jurisprudência , Ecossistema , Pesqueiros/economia , Pesqueiros/história , Pesqueiros/legislação & jurisprudência , Peixes , História do Século XX , História do Século XXI , Política Pública
8.
Med Sci Monit ; 21: 3371-9, 2015 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-26537625

RESUMO

BACKGROUND: The tumor susceptibility gene 101 (TSG101) was originally identified as a tumor-suppressor gene that mediates many molecular and biological processes, such as ubiquitination, endosomal trafficking, cell survival, and virus budding, but its role in hepatocellular carcinoma (HCC) is currently unknown. MATERIAL AND METHODS: We assessed the expression of TSG101 in HCC and paracancerous tissues using qPCR. Then, we used the TSG101-specific siRNA mix to disrupt the expression of TSG101 to investigate the subsequent effect on human hepatoma-7 (Huh7) cells. Western blot was used to detect the protein expression of TSG101 and other molecules. Cell growth assay was performed using CCK8. Transwell assay was used to investigate the migration and invasion ability of Huh7 cells after transfection with of TSG101 siRNA. Flow cytometry was used to estimate the effect of TSG101 knockdown on cell cycle and apoptosis. Confocal laser scanning microscopy was used to observe the actin filaments change and the formation of autophagy. RESULTS: TSG101 was over-expressed in HCC tissues. TSG101 silence was able to suppress Huh7 cell proliferation, migration, and invasion. Furthermore, silencing of TSG101 could induce cell cycle arrest at G1 phase and inhibit the expression of cyclin A and cyclin D, while up-regulating the expression of CDK2. The mechanism might be induction of autophagic cell death and inactivation of Akt and ERK1/2. CONCLUSIONS: TSG101 plays an important role in the development of HCC and may be a target for molecular therapy.


Assuntos
Autofagia/genética , Carcinoma Hepatocelular/genética , Pontos de Checagem do Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Inativação Gênica , Neoplasias Hepáticas/genética , Fatores de Transcrição/genética , Apoptose , Carcinoma Hepatocelular/terapia , Morte Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ciclina A/metabolismo , Ciclina D/metabolismo , Proteínas de Ligação a DNA/fisiologia , Complexos Endossomais de Distribuição Requeridos para Transporte/fisiologia , Citometria de Fluxo , Fase G1 , Deleção de Genes , Humanos , Microscopia Confocal , Microscopia de Fluorescência , Invasividade Neoplásica , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição/fisiologia
9.
Mol Cancer ; 14: 177, 2015 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-26438046

RESUMO

BACKGROUND: Apoptosis-stimulating of p53 protein 2 (ASPP2) is one of the ASPP family members and it has been reported to be associated with human cancer. However, the role of it in pancreatic cancer is still not clear. METHODS: We analyzed the expression level of ASPP2 in cancer tissue samples with RT-qPCR, Western Blotting assay and immunohistochemistry staining. We studied the biological function of ASPP2 and its mechanism with gene overexpression and gene silencing technologies. We determined the sensitivity of pancreatic cells with differential ASPP2 level to gemcitabine and whether autophagy inhibition affected the gemcitabine resistance, both in vitro and in vivo. RESULTS: Expression of ASPP2 was downregulated in cancerous tissues in comparison with para-cancerous tissues. ASPP2 expression was linked to clinical outcomes in patients and down-regulation of ASPP2 increased cell proliferation, autophagic flux, the activity of AMP Kinase of pancreatic cancer cells and vice versa. Knockdown of ASPP2 results in increased resistance to gemcitabine, which was attributed to the enhanced autophagy. CONCLUSIONS: ASSP2 expression is lower in cancerous tissues and decreased ASPP2 lead to higher cancer cells proliferation and autophagic flux, which contribute to the gemcitabine resistance.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/farmacologia , Regulação para Baixo , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Gencitabina
10.
Biol Res ; 48: 23, 2015 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-25943891

RESUMO

BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore, it is an important goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Hepatócitos/metabolismo , Hepcidinas/genética , Fatores de Transcrição SOXB1/genética , Anemia/genética , Anemia/metabolismo , Sítios de Ligação , Proteína Morfogenética Óssea 2/metabolismo , Técnicas de Silenciamento de Genes , Vetores Genéticos , Células Hep G2 , Hepcidinas/metabolismo , Humanos , Interleucina-6/metabolismo , Ferro/metabolismo , Luciferases , Plasmídeos/genética , Regiões Promotoras Genéticas/genética , Fatores de Transcrição SOXB1/metabolismo
11.
PLoS One ; 10(3): e0120694, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25815885

RESUMO

During chemotherapy, drug resistance caused by autophagy remains a major challenge to successful treatment of cancer patients. The purpose of this study is to show that ulinastatin (UTI), a trypsin inhibitor, could reduce the resistance of liver cancer cells to chemotherapeutic agent epirubicin (EPI). We achieved this conclusion by analyzing the effect of EPI alone or UTI plus EPI on SMMC-7721 and MHCC-LM3 liver cancer cells. We also generated an EPI-resistant liver cancer cell line (MHCC-LM3er cells), and found that UTI could sensitize the LM3er cells to EPI. Autophagy usually functions to protect cancer cells during chemotherapy. Our study showed that UTI inhibited the autophagy induced by EPI in liver cancer cells, which promoted apoptosis, and therefore, reduced the resistance of the cancer cells to EPI. Further studies showed that the UTI-mediated inhibition on autophagy was achieved by inhibiting transcriptional factor nuclear factor-κB (NF-κB) signaling pathway. To verify our results in vivo, we injected MHCC-LM3 liver cancer cells or EPI-resistant LM3er cells into mice, and found that EPI could only effectively inhibit the growth of tumor in MHCC-LM3 cell-injected mice, but not in LM3er cell-injected mice. However, when UTI was also administered, the growth of tumor was inhibited in the MHCC-LM3er cell-injected mice as well. Our results suggest that UTI may be used in combination with anti-cancer drugs, such as EPI, to improve the outcome of cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Epirubicina/farmacologia , Glicoproteínas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Inibidores da Tripsina/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Biol. Res ; 48: 1-8, 2015. graf
Artigo em Inglês | LILACS | ID: biblio-950787

RESUMO

BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore,itis animportant goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.


Assuntos
Humanos , Regulação Neoplásica da Expressão Gênica/genética , Hepatócitos/metabolismo , Fatores de Transcrição SOXB1/genética , Hepcidinas/genética , Plasmídeos/genética , Sítios de Ligação , Interleucina-6/metabolismo , Regiões Promotoras Genéticas/genética , Proteína Morfogenética Óssea 2/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Técnicas de Silenciamento de Genes , Células Hep G2 , Hepcidinas/metabolismo , Vetores Genéticos , Anemia/genética , Anemia/metabolismo , Ferro/metabolismo , Luciferases
13.
Mol Cancer Ther ; 13(8): 2127-37, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24928851

RESUMO

Mesenchymal stem cells (MSC) represent a new tool for delivery of therapeutic agents to cancer sites because of their strong tropism toward tumors. IL15 has demonstrated a potent antitumor activity in various animal models as well as clinical trials. However, because of its short half-life, effective therapeutic effects usually require a high dose, which often results in undesired side effects; thus, new strategies for overcoming this disadvantage are needed. In this study, human MSCs were isolated from umbilical cord blood as delivery vehicles and transduced with lentivirus vector expressing murine IL15 (MSC-IL15). In vitro assays of lymphocyte activation and proliferation demonstrated that IL15 produced by MSCs was biofunctional. In syngeneic mice bearing Pan02 pancreatic tumors, systemic administration of MSC-IL15 significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice, which were associated with tumor cell apoptosis, and natural killer (NK)- and T-cell accumulation. Furthermore, we confirmed that MSC-IL15 could migrate toward tumor and secreted IL15 in tumor-specific sites. Depletion of NK and CD8(+) T cells abolished the antitumor activity of MSC-IL15, suggesting that NK and CD8(+) T cells play a key role for MSC-IL15-mediated effect. Interestingly, cured mice after MSC-IL15 treatment were resistant to Pan02 pancreatic tumor rechallenge, and adoptive transfer of lymphocytes from cured mice also could cause rejection of Pan02 tumor inoculation in naïve mice, indicating that MSC-IL15 induced tumor-specific T-cell immune memory response. Overall, these data support that MSCs producing IL15 might represent an innovative strategy for therapy of pancreatic tumor.


Assuntos
Carcinoma Ductal Pancreático/terapia , Transplante de Células-Tronco Mesenquimais , Neoplasias Pancreáticas/terapia , Transferência Adotiva , Animais , Linfócitos T CD8-Positivos/imunologia , Carcinoma Ductal Pancreático/imunologia , Linhagem Celular Tumoral , Movimento Celular , Sangue Fetal/citologia , Humanos , Interleucina-15/metabolismo , Células Matadoras Naturais/imunologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Pancreáticas/imunologia
14.
Nat Med ; 20(6): 596-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24859531

RESUMO

Pancreatic adenosquamous carcinoma (ASC) is an enigmatic and aggressive tumor that has a worse prognosis and higher metastatic potential than its adenocarcinoma counterpart. Here we report that ASC tumors frequently harbor somatically acquired mutations in the UPF1 gene, which encodes the core component of the nonsense-mediated RNA decay (NMD) pathway. These tumor-specific mutations alter UPF1 RNA splicing and perturb NMD, leading to upregulated levels of NMD substrate mRNAs. UPF1 mutations are, to our knowledge, the first known unique molecular signatures of pancreatic ASC.


Assuntos
Processamento Alternativo/genética , Carcinoma Adenoescamoso/genética , Degradação do RNAm Mediada por Códon sem Sentido/genética , Neoplasias Pancreáticas/genética , Transativadores/genética , Sequência de Bases , Componentes do Gene , Células HEK293 , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Dados de Sequência Molecular , Mutagênese , Mutação/genética , RNA Helicases , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Neoplasias Pancreáticas
15.
BMC Gastroenterol ; 14: 62, 2014 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-24708487

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in human population. The 6-fluoro-3-formylchromone (FCC) has been shown to have anti-tumor activity against various tumor cells. However, the effects of FCC on HCC cell lines have not yet been reported. This study aims to research the effects of FCC on HCC and advance the understanding of the molecular mechanism. METHODS: HCC cell line SMMC-7721 was treated with FCC at various concentrations (0, 2, 5, 10, and 20 µg/ml) for 24, 48 and 72 h, respectively. The proliferations of SMMC-7721 cells were measured by MTT assays. After cultured 24 hours, cell cycle distribution and apoptosis were determined by flow cytometry. However, the expression levels of PCNA, Bax and Bcl-2 were measured by western blotting after 48 hours. RESULTS: FCC displayed a dose- and time-dependent inhibition of the SMMC-7721 cell proliferations in vitro. It also induced apoptosis with 45.4% and caused cell accumulation in G0/G1 phase with 21.5%. PCNA and Bcl-2 expression was significantly suppressed by FCC in a dose-dependent manner (P < 0.05), while Bax expression was increased. CONCLUSIONS: FCC could significantly inhibit HCC cell growth in vitro through cell cycle arrest and inducing apoptosis by suppressing PCNA expression and modulating the Bax/Bcl-2 ratio.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Compostos de Flúor/farmacologia , Formiatos/farmacologia , Neoplasias Hepáticas , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Antígeno Nuclear de Célula em Proliferação/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
17.
Clin Exp Hypertens ; 36(5): 321-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24047449

RESUMO

OBJECTIVES: This study documented the prevalence and clinical features of white coat hypertension (WCH) among Chinese Han patients with type 2 diabetes mellitus (T2DM). METHODS: Clinic and ambulatory blood pressure (BP) measurements were compared in 856 patients with T2DM to determine the frequency of WCH (WCH was defined as clinical blood pressure ≥140/90 mmHg and daytime blood pressure <135/85 mmHg and/or 24-h ambulatory BP (ABP) mean value of <130/80 mmHg on ambulatory BP monitoring (ABPM). Weight, waist circumference (WC), body mass index (BMI), waist to height ratio (WHtR), fasting blood glucose, glycosylated hemoglobin level and circadian BP patterns were also measured to find clinical features predictive of WCH in T2DM. RESULTS: The prevalence of WCH was 7.36% (63/856) in the overall population, 6.13% (29/473) in male and 8.88% (34/383) in female (p < 0.05). WCH accounted for 14.03% (63/449) of diagnosed hypertension. Age, course of T2DM, male WC were independent protective factors, whereas female sex, smoking and alcohol consumption were independent risk factors for WCH in T2DM. Non-dippers and reverse dippers made up larger proportion of the WCH group (p < 0.01). CONCLUSION: WCH is relatively common among T2DM patients, it is a unique condition distinct from essential hypertension (EH), and WCH patients also exhibit significant differences in clinical parameters.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão do Jaleco Branco/epidemiologia , Adulto , Povo Asiático , Determinação da Pressão Arterial/métodos , Monitorização Ambulatorial da Pressão Arterial , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Hipertensão Essencial , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Hipertensão do Jaleco Branco/complicações , Hipertensão do Jaleco Branco/diagnóstico
18.
J Diabetes Complications ; 27(1): 82-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22906551

RESUMO

OBJECTIVE: The prevalence and clinical features of masked hypertension (MH) in type 2 diabetes mellitus patients (T(2)DM) were investigated to define clinical indices which may aid diagnosis and treatment. METHODS: Clinical blood pressure (CBP) and ambulatory blood pressure (ABP) were measured in 856 T(2)DM patients to differentiate normotensive (NT), essential hypertensive (EH), and MH. Waist circumference (WC), abdominal circumference (AC), body mass index (BMI), waist to height ratio (WHtR), fasting blood glucose (FBG), and glycated hemoglobin levels were measured and compared between BP groups. RESULTS: In total, 359 patients had normal CBP, of which 13.37% were diagnosed with MH based on established criteria. Males had significantly higher rates of MH (15.30%) than females (11.36%) (P=0.036). The MH detection rate increased with age and T(2)DM duration. There were no significant differences in BMI, WC or WHtR between total MH and EH groups. MH females, however, had lower BMIs than female EH females (P=0.023). Smoking, alcohol, and familial EH history were lower in MH than EH patients (smoking, P=0.029; alcohol ,P=0.001; and EH history, P=0.000), while BMI (male, P=0.037, female, P=0.015), WC (male, P=0.012, female, P=0.021), WHtR (P=0.011), smoking (P=0.016), and alcohol consumption (P=0.000) were higher in MH than NT patients. BMI, WHtR, 6-15 year disease course of diabetes, smoking and alcoholism were independent risk factors of T(2)DM complicated with MH. The dipper BP circadian pattern was significantly lower in MH than NT patients (P=0.001). The non-dipper pattern was lower in MH than EH (P=0.018) but higher than in NT (P=0.000). CONCLUSIONS: A significant fraction of T(2)DM patients were diagnosed with MH. Clinical presentation also contrasted sharply from EH, MH is a specific blood pressure status that may severely damage target organs in T(2)DM.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão Mascarada/epidemiologia , Adulto , Fatores Etários , Idoso , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 2/complicações , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Hipertensão Mascarada/diagnóstico , Hipertensão Mascarada/etiologia , Pessoa de Meia-Idade , Prevalência
19.
Hepatogastroenterology ; 60(121): 187-90, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22784943

RESUMO

BACKGROUND/AIMS: Pancreatic body and tail carcinoma (PBTC) is an aggressive disease with a low resectability rate. Celiac axis infiltration usually contraindicates resection. Extended distal pancreatectomy with combined en bloc celiac axis resection (DP-CAR, also named Appleby operation) was described as a new concept for the curative treatment of these tumors. The aim of this study was to analyze the results of DP-CAR in PBTC. METHODOLOGY: Analyze by summarizing the 24 cases of PBTC during October 2005 to August 2010 in the pancreatic surgery of our hospital and analyzing the clinical manifestations, surgical processing, pathological effects and survival rate of the patients. RESULTS: The postoperative mortality rate was 0%, despite a high morbidity rate (54%). Preoperative intractable abdominal and/or back pain in all the patients was completely alleviated immediately after surgery. During the follow-up survey among all the patients of 2 to 37 months (with an average follow-up survey of 12.67 months), no patient was still alive, with the median survival of 9.25 months. Estimated overall 1- and 3-year survival rates were 46% and 4%, respectively. CONCLUSIONS: DP-CAR offers a high resectability rate without increasing the mortality rate given skilled surgical technique.


Assuntos
Artéria Celíaca/cirurgia , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Taxa de Sobrevida
20.
Cancer Sci ; 103(10): 1756-63, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22716017

RESUMO

Cancer cells can metastasize throughout the body by various mechanisms, including the lymphatic system, resulting in tumor-induced lymphangiogenesis that can profoundly affect patient survival. The aim of the present study was to examine the role of lymphangiogenesis in the metastasis of pancreatic cancer to the peripheral nerve plexus. Immunohistochemistry was performed to analyze specimens obtained from 70 ductal adenocarcinoma patients. The markers used included lymphangiogenic factor vascular endothelial growth factor (VEGF)-C, the lymphatic-specific marker D2-40, and cytokeratin 19, an independent prognostic factor for pancreatic tumors. The relationship between survival rate and invasion of both the lymphatic vessels and peripancreatic nerve plexus (PNP) was evaluated, with clearly elevated lymphatic vessel density (LVD) in tissues adjacent to the cancer tissues. In fact, LVD levels were higher in adjacent tissues than in localized cancer tissues, and lymphatic vessel invasion into tissues adjacent to the tumor was significantly correlated with both PNP invasion (P = 0.005) and lymph node metastasis (P = 0.010). Correspondingly, LVD in tissues adjacent to the tumor was correlated with both invasion of lymphatic vessels surrounding the tumor (P = 0.024) and VEGF-C expression (P = 0.031); in addition, VEGF-C expression was correlated with invasion of lymphatic vessels around the tumor (P = 0.004). Survival rates were significantly lower in patients in whom there was peritumor lymphatic vessel invasion (P < 0.001), extrapancreatic nerve plexus invasion (P = 0.001), and/or lymph node metastasis (P < 0.001). Based on these results, lymphatic invasion associated with adjacent tumor growth likely contributes to the development of metastatic tumors that invade the PNP.


Assuntos
Carcinoma Ductal Pancreático/patologia , Linfangiogênese/fisiologia , Metástase Linfática/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Fator C de Crescimento do Endotélio Vascular/análise , Fator C de Crescimento do Endotélio Vascular/biossíntese
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