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1.
Br J Cancer ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294438

RESUMO

BACKGROUND: The clinical validity of the multifactorial BOADICEA model for epithelial tubo-ovarian cancer (EOC) risk prediction has not been assessed in a large sample size or over a longer term. METHODS: We evaluated the model discrimination and calibration in the UK Biobank cohort comprising 199,429 women (733 incident EOCs) of European ancestry without previous cancer history. We predicted 10-year EOC risk incorporating data on questionnaire-based risk factors (QRFs), family history, a 36-SNP polygenic risk score and pathogenic variants (PV) in six EOC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1 and PALB2). RESULTS: Discriminative ability was maximised under the multifactorial model that included all risk factors (AUC = 0.68, 95% CI: 0.66-0.70). This model was well calibrated in deciles of predicted risk with calibration slope=0.99 (95% CI: 0.98-1.01). Discriminative ability was similar in women younger or older than 60 years. The AUC was higher when analyses were restricted to PV carriers (0.76, 95% CI: 0.69-0.82). Using relative risk (RR) thresholds, the full model classified 97.7%, 1.7%, 0.4% and 0.2% women in the RR < 2.0, 2.0 ≤ RR < 2.9, 2.9 ≤ RR < 6.0 and RR ≥ 6.0 categories, respectively, identifying 9.1 of incident EOC among those with RR ≥ 2.0. DISCUSSION: BOADICEA, implemented in CanRisk ( www.canrisk.org ), provides valid 10-year EOC risks and can facilitate clinical decision-making in EOC risk management.

2.
Environ Sci Pollut Res Int ; 31(17): 26170-26181, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38498134

RESUMO

The wet flue gas desulfurization (WFGD) system of coal-fired power plants shows a good removal effect on condensable particulate matter (CPM), reducing the dust removal pressure for the downstream flue gas purification devices. In this work, the removal effect of a WFGD system on CPM and its organic pollutants from a coal-fired power plant was studied. By analyzing the organic components of the by-products emitted from the desulfurization tower, the migration characteristics of organic pollutants in gas, liquid, and solid phases, as well as the impact of desulfurization towers on organic pollutants in CPM, were discussed. Results show that more CPM in the flue gas was generated by coal-fired units at ultra-low load, and the WFGD system had a removal efficiency nearly 8% higher than that at full load. The WFGD system had significant removal effect on two typical esters, especially phthalate esters (PAEs), with the highest removal efficiency of 49.56%. In addition, the WFGD system was better at removing these two esters when the unit was operating at full load. However, it had a negative effect on n-alkanes, which increased the concentration of n-alkanes by 8.91 to 19.72%. Furthermore, it is concluded that the concentration distribution of the same type of organic pollutants in desulfurization wastewater was similar to that in desulfurization slurry, but quite different from that in coal-fired flue gas. The exchange of three organic pollutants between flue gas and desulfurization slurry was not significant, while the concentration distribution of organic matters in gypsum was affected by coal-fired flue gas.


Assuntos
Poluentes Atmosféricos , Poluentes Ambientais , Material Particulado/análise , Poluentes Atmosféricos/análise , Gases , Centrais Elétricas , Carvão Mineral , Alcanos
3.
J Am Chem Soc ; 145(37): 20189-20195, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37647087

RESUMO

Sulfation widely exists in the eukaryotic proteome. However, understanding the biological functions of sulfation in peptides and proteins has been hampered by the lack of methods to control its spatial or temporal distribution in the proteome. Herein, we report that fluorosulfate can serve as a latent precursor of sulfate in peptides and proteins, which can be efficiently converted to sulfate by hydroxamic acid reagents under physiologically relevant conditions. Photocaging the hydroxamic acid reagents further allowed for the light-controlled activation of functional sulfopeptides. This work provides a valuable tool for probing the functional roles of sulfation in peptides and proteins.


Assuntos
Proteoma , Sulfatos , Peptídeos , Eucariotos , Ácidos Hidroxâmicos , Óxidos de Enxofre
4.
Perioper Med (Lond) ; 12(1): 42, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37468994

RESUMO

We aimed to analyse postoperative cognitive dysfunction (POCD) incidence and risk factors in elderly adults who underwent surgery for oral malignancies. A total of 112 elderly patients (aged ≥ 55 years) were selected for expanded resection of oral malignancy and cervical lymphatic dissection at our institution from December 2020 to December 2021. Participants were cognitively evaluated using the neuropsychological test scale 1 day before and 7 days after surgery to determine whether they had developed POCD. Based on whether POCD occurred 7 days after surgery, patients were classified into the POCD and non-POCD groups. Logistic regression was applied to perioperative factors to analyse the risk factors for POCD onset. Seven days after surgery for oral malignancy, there were 37 (33.1%) POCD morbidities. Multiple factor logistic regression analysis revealed that venerable age (odds ratio [OR] = 1.269, 95% confidence interval [CI] 1.056-1.525, P < 0.05), low education levels (OR = 0.792, 95% CI 0.644-0.974, P < 0.05), hypertension (OR = 4.153, 95% CI 1.335-12.732, P < 0.05), dyssomnia (OR = 1.272, 95% CI 1.001-1.617, P < 0.05), prolonged anaesthesia (OR = 1.009, 95% CI 1.001-1.018, P < 0.05), and intraoperative hypotension (OR = 5.512, 95% CI 1.240-24.506, P < 0.05) increased the POCD risk in elderly patients who underwent surgery for oral malignancies. Venerable age, low knowledge reserve, hypertension, dyssomnia, prolonged anaesthesia, and intraoperative hypotension are independent risk factors for POCD in elderly patients with oral malignancies.

5.
J Med Chem ; 66(14): 9537-9560, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37409679

RESUMO

Aldo-keto reductase 1C3 (AKR1C3) is correlated with tumor development and chemotherapy resistance. The catalytic activity of the enzyme has been recognized as one of the important factors in inducing anthracycline (ANT) resistance in cancer cells. Inhibition of AKR1C3 activity may provide a promising approach to restore the chemosensitivity of ANT-resistant cancers. Herein, a series of biaryl-containing AKR1C3 inhibitors has been developed. The best analogue S07-1066 selectively blocked AKR1C3-mediated reduction of doxorubicin (DOX) in MCF-7 transfected cell models. Furthermore, co-treatment of S07-1066 significantly synergized DOX cytotoxicity and reversed the DOX resistance in MCF-7 cells overexpressing AKR1C3. The potential synergism of S07-1066 over DOX cytotoxicity was demonstrated in vitro and in vivo. Our findings indicate that inhibition of AKR1C3 potentially enhances the therapeutic efficacy of ANTs and even suggests that AKR1C3 inhibitors may serve as effective adjuvants to overcome AKR1C3-mediated chemotherapy resistance in cancer treatment.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Membro C3 da Família 1 de alfa-Ceto Redutase , Doxorrubicina/farmacologia , Antraciclinas , Antibióticos Antineoplásicos/farmacologia , Células MCF-7 , 3-Hidroxiesteroide Desidrogenases/farmacologia , Hidroxiprostaglandina Desidrogenases , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia
6.
Front Med (Lausanne) ; 10: 1201866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293309

RESUMO

Background: In recent years, the number of people using mobile applications to promote health and welfare has exponentially increased. However, there are fewer applications in the field of ERAS. How to promote the rapid rehabilitation of patients with malignant tumor surgery during perioperative period and the mastery of its long-term nutritional state is a problem to be solved. Objective: The purpose of this study is to design and develop a mobile application, and use Internet technology to better manage nutritional health to achieve rapid recovery of patients with malignant tumor surgery. Methods: This study is divided into three stages: (1) Design: use participating design to make the MHEALTH APP adapt to the clinical practice of nutritional health management; (2) Development: the WeChat Applet of Nutrition and Health Assessment (WANHA) developed using the Internet technology development, and web management programs. (3) Procedure test: patients and medical staff evaluate WANHA's quality (UMARS), availability (SUS), and satisfaction, and conduct semi-structured interviews. Results: In this study, 192 patients with malignant tumor surgery, 20 medical staff used WANHA. Patients with nutritional risks are supported by supporting treatment. The results show that patients who have not been treated during the perioperative period, the incidence of postoperative complications (22.4%) and the average hospitalization time after surgery decreased significantly. The incidence of nutritional risks is nearly more than the preoperative level. 45 patients and 20 medical staff participated in the survey of WANHA's SUS, UMARS, and satisfaction. In the interview, most patients and medical personnel believe that the procedure can improve the current medical services and nutritional health knowledge levels, promote the communication of medical staff and patients, and strengthen the nutritional health management of patients with malignant tumors under the concept of ERAS. Conclusion: WeChat Applet of Nutrition and Health Assessment is a MHEALTH APP that enhances the nutrition and health management of patients with perioperative period. It can play a huge role in improving medical services, increasing patient satisfaction, and ERAS.

7.
Nanotechnology ; 34(24)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-36878001

RESUMO

In order to prevent drugs from being captured and degraded by the acidic environment of organelles, such as lysosomes, after entering cells, this study designed and synthesized a novel carrier amphiphilic polypeptide (DGRHHHLLLAAAA), designated P13, for use as a tumor-targeting drug delivery vehicle. The P13 peptide was synthesized by the solid phase synthesis method, and its self-assembly behavior and drug-loading capacity in aqueous solution were studied and characterizedin vitro. Doxorubicin (DOX) was loaded by dialysis method, and P13 and DOX were mixed at a mass ratio of 6:1 to form regular rounded globules. The acid-base buffering capacity of P13 was investigated determined by acid-base titration. The results revealed that P13 had excellent acid-base buffering capacity, a critical micelle concentration value of about 0.000 21 g l-1, and the particle size of P13-Dox nanospheres was 167 nm. The drug encapsulation efficiency and drug loading capacity of micelles were 20.40 ± 1.21% and 21.25 ± 2.79%, respectively. At the concentration of 50µg ml-1of P13-DOX , the inhibition rate was 73.35%. The results of thein vivoantitumor activity assay in mice showed that P13-DOX also exhibited excellent inhibitory effect on tumor growth, compared with the tumor weight of 1.1 g in the control group, the tumor weight in the P13-DOX-treated group was only 0.26 g. Additionally, the results of hematoxylin and eosin staining of the organs showed that P13-DOX had no damaging effect on normal tissues. The novel amphiphilic peptide P13 with proton sponge effect designed and prepared in this study is expected to be a promising tumor-targeting drug carrier with excellent application potential.


Assuntos
Neoplasias , Prótons , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Micelas , Peptídeos/farmacologia , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
8.
Front Med (Lausanne) ; 9: 1001213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530879

RESUMO

Background: High-flow nasal oxygenation (HFNO) has been suggested as an alternative oxygenation method during procedural sedation. This randomized, non-inferiority trial evaluated the safety and efficacy of HFNO compared with laryngeal mask airway (LMA) in pediatric ambulatory oral surgery under deep sedation. Methods: In total, 120 children aged 2-7 years (weight: 10-30 kg) were equally assigned into two groups, namely, HFNO with propofol total intravenous anesthesia infusion (HFNO-IV) or LMA with propofol total intravenous anesthesia infusion (LMA-IV). The primary objective was to monitor carbon dioxide (CO2) accumulation during perioperative surgery. Secondary objectives included monitoring transcutaneous oxygen saturation, grade exposure to the surgical field, perioperative adverse events, or other events. The predefined non-inferiority margin was 7 mmHg. During the COVID-19 pandemic, a novel WeChat applet was implemented to gather follow-up data after discharge. Results: Non-inferiority could be declared for HFNO relative to LMA (mean difference in transcutaneous CO2 (TcCO2) = -1.4 mmHg, 95% CI: -2.9, 0.1 mmHg; P > 0.05). The pre-surgical TcCO2 of the HFNO-IV group (45.4 ± 4.5 mmHg) was similar to that of the LMA-IV group (44.0 ± 3.5 mmHg), within the clinically acceptable normal range. All the children maintained SpO2 levels of >97%. The surgical field exposure score of the HFNO group was significantly better than that of the LMA group. There was no significant difference between the two groups regarding risk or adverse events. Conclusion: HFNO was not inferior to LMA for maintaining oxygenation and ventilation in patients undergoing pediatric ambulatory oral surgery under deep sedation under strict isolation from the oral cavity to the upper airway.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36412607

RESUMO

INTRODUCTION: Zoledronic acid (ZA) is a widely used bisphosphonate compound for the prevention of skeletal metastasis-associated osteolysis and treatment of post-menopause osteoporosis. Acute kidney injury is one of the commonly described renal complications. Electrolytes disorder has also been reported relevant to ZA exposure and nephrotoxicity. Syndrome of persistent hypophosphatemia, hypokalemia and metabolic acidosis is regarded as the initial signs of acute kidney injury. CASE PRESENTATION: We reported a 64-year-old female with bone metastasis from lung adenocarcinoma who received a 5-year history of 4-week cycle ZA infusion. She initially presented symptomatic severe hypophosphatemia and was finally identified with ZA-induced generalized tubular dysfunction as Fanconi's syndrome and distal renal tubular acidosis. Renal pathological findings revealed toxic renal tubular necrosis. The ZA infusion was thus extended to an 8-week cycle with oral phosphate supplementation and alfacalcidol. Although periodic changes pre- and post-ZA infusion existed yet, hypophosphatemia was effectively improved and the rapid decline of eGFR was partially delayed. We reviewed the literature and mainly summarized the characteristics of bisphosphonates-associated hypophosphatemia. Moderate hypophosphatemia was more frequently mentioned in contrast to severe cases being predisposed to be reported. And progressive hypophosphatemia serves as an early sign of kidney injury. CONCLUSION: Progressive electrolyte disorders and CKD were the long-term renal outcome of the current patient. We would like to arouse more attention to electrolytes imbalance related to early ZA-induced kidney injury and emphasize the significance of close monitoring.

10.
Food Chem Toxicol ; 169: 113398, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36096291

RESUMO

It is necessary to determine whether synthetic dyes are present in food since their excessive use has detrimental effects on human health. For the simultaneous assessment of tartrazine and Patent Blue V, a novel electrochemical sensing platform was developed. As a result, two artificial azo colorants (Tartrazine and Patent Blue V) with toxic azo groups (-NN-) and other carcinogenic aromatic ring structures were examined. With a low limit of detection of 0.06 µM, a broad linear concentration range 0.09µM to 950µM, and a respectable recovery, scanning electron microscopy (SEM) was able to reveal the excellent sensing performance of the suggested electrode for patent blue V. The electrochemical performance of an electrode can be characterized using cyclic and differential pulse voltammetry, and electrochemical impedance spectroscopy. Moreover, the classification model was created by applying binary classification assessment using enhanced artificial intelligence comprises of support vector machine (SVM) and Genetic Algorithm (GA), respectively, a support vector machine and a genetic algorithm, which was then validated using the 50 dyes test set. The best binary logistic regression model has an accuracy of 83.2% and 81.1%, respectively, while the best SVM model has an accuracy of 90.3% for the training group of samples and 81.1% for the test group (RMSE = 0.644, R2 = 0.873, C = 205.41, and = 5.992). According to the findings, Cu-BTC MOF (copper (II)-benzene-1,3,5-tricarboxylate) has a crystal structure and is tightly packed with hierarchically porous nanomaterials, with each particle's edge measuring between 20 and 37 nm. The suggested electrochemical sensor's analytical performance is suitable for foods like jellies, condiments, soft drinks and candies.


Assuntos
Inteligência Artificial , Compostos Azo , Técnicas Eletroquímicas , Corantes de Alimentos , Contaminação de Alimentos , Corantes de Rosanilina , Tartrazina , Humanos , Compostos Azo/análise , Compostos Azo/isolamento & purificação , Técnicas Eletroquímicas/métodos , Eletrodos , Corantes de Alimentos/análise , Corantes de Alimentos/isolamento & purificação , Contaminação de Alimentos/prevenção & controle , Corantes de Rosanilina/análise , Corantes de Rosanilina/isolamento & purificação
11.
Oncogene ; 41(31): 3846-3858, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35773412

RESUMO

Aldo-keto reductase family 1 member C3 (AKR1C3) serves as a contributor to numerous kinds of tumors, and its expression is elevated in patients with hepatocellular carcinoma (HCC). However, the biological function of AKR1C3 in HCC remains unclear. Here we investigated the role of AKR1C3 in liver carcinogenesis using in vitro and in vivo models. We determined that AKR1C3 is frequently increased in HCC tissues with poor prognosis. Genetically manipulated cells with AKR1C3 construction were examined to highlight the pro-tumoral growth of both wild-type AKR1C3 and mutant in vitro and in vivo. We observed promising treatment effects of AKR1C3 shRNA by intratumoral injection in mice. Mechanically, we demonstrated that the transcription factor heterodimer NRF2/MAFG was able to bind directly to AKR1C3 promoter to activate its transcription. Further, AKR1C3 stabilized PARP1 by decreasing its ubiquitination, which resulted in HCC cell proliferation and low sensitivity of Cisplatin. Moreover, we discovered that the tumorigenic role of AKR1C3 was non-catalytic dependent and the NRF2/MAFG-AKR1C3-PARP1 axis might be one of the important proliferation pathways in HCC. In conclusion, blockage of AKR1C3 expression provides potential therapeutic benefits against HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , 3-Hidroxiesteroide Desidrogenases/genética , Membro C3 da Família 1 de alfa-Ceto Redutase/metabolismo , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Hidroxiprostaglandina Desidrogenases/genética , Neoplasias Hepáticas/genética , Fator de Transcrição MafG/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Repressoras/metabolismo
12.
Phytother Res ; 36(7): 2940-2951, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35537702

RESUMO

Angiogenesis plays a pivotal role in the recovery of neurological function after ischemia stroke. Herein, we investigated the effect of trilobatin (TLB) on angiogenesis after cerebral ischemia-reperfusion injury (CIRI). The effect of TLB on angiogenesis after CIRI were investigated in mouse brain microvascular endothelium bEnd.3 cells and middle cerebral artery occlusion (MCAO)-induced CIRI rat model. The cell proliferation and angiogenesis were observed using immunofluorescence staining. The cell cycle, expressions of cell cycle-related proteins and SIRT 1-7 were determined by flow cytometry and western blot, respectively. The binding affinity of TLB with SIRT7 was predicted by molecular docking. The results showed that TLB concentration-dependently promoted bEnd.3 cell proportion in the S-phase. TLB significantly increased the protein expressions of SIRT6, SIRT7, and VEGFA, but not affected SIRT1-SIRT5 protein expressions. Moreover, TLB not only dramatically alleviated neurological impairment after CIRI, but also enhanced post-stroke neovascularization and newly formed functional vessels in cerebral ischemic penumbra. Furthermore, TLB up-regulated the protein expressions of CDK4, cyclin D1, VEGFA and its receptor VEGFR-2. Intriguingly, TLB not only directly bound to SIRT7, but also increased SIRT7 expression at day 28. Our findings reveal that TLB promotes cerebral microvascular endothelial cells proliferation, and facilitates angiogenesis after CIRI via mediating SIRT7/VEGFA signaling pathway in rats. Therefore, TLB might be a novel restorative agent to rescue ischemia stroke.


Assuntos
Flavonoides , Polifenóis , Traumatismo por Reperfusão , Sirtuínas , Animais , Células Endoteliais/metabolismo , Flavonoides/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Neovascularização Patológica , Polifenóis/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais , Sirtuínas/metabolismo , Fator A de Crescimento do Endotélio Vascular
13.
Chemosphere ; 294: 133668, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35063556

RESUMO

Wet flue gas desulfurization (WFGD) in coal-fired power plants has a great impact on the emission of particulate matter, including filterable particulate matter (FPM) and condensable particulate matter (CPM). In this paper, CPM and FPM in flue gas before and after WFGD in coal-fired power plants were sampled in parallel. FPM was tested according to ISO standard 23210-2009, and CPM was tested according to U.S. EPA Method 202. A method for quantitatively analyzing fatty acid methyl esters in CPM was established, and the removal capacity of fatty acid methyl esters and phthalate esters by WFGD in a typical coal-fired unit was compared. Results show that WFGD has a significant effect on particle size distribution, concentration, and chemical composition. WFGD has a high removal efficiency of inorganic components in CPM, up to 54.74%. CPM contains a variety of organic compounds, including hydrocarbons, esters, siloxanes, halogenated hydrocarbons, and so on. In particular, esters are an important component in CPM, whose concentration tends to decrease after WFGD. Furthermore, a total of 11 fatty acid methyl esters and 5 phthalate esters were detected in CPM before and after WFGD. Noted that fatty acid methyl esters account for 13.38% of CPM, which make a higher contribution to the concentration of particulate matter than phthalate esters, while WFGD has a stronger control effect on the removal of phthalates.


Assuntos
Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , Carvão Mineral/análise , Gases , Material Particulado/análise , Centrais Elétricas
14.
Int J Clin Exp Pathol ; 14(3): 348-354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33786151

RESUMO

BACKGROUND: To explore the need for the high-risk and general population to undergo endoscopy and the best age for these two groups to do so. MATERIAL AND METHODS: Data on 35,525 patients who underwent endoscopy in the Endoscopic Center of Shanxi Cancer Hospital and associated medical group hospitals from January 2016 to December 2019 were collected. Two aspects of the high-risk and general population were analyzed retrospectively: 1. The detection rate of precancerous diseases. 2. The difference and distribution of the detection rate in different genders, different ages, and different pathologic types. RESULTS: A total of 35,525 patients, 24,185 in the general population and 11,340 in the high-risk population, were examined by electronic gastroscopy and colonoscopy simultaneously. Of these, 20,659 were men and 14,866 were women. The detection rate of gastric diseases (gastric cancer, gastric polyp, gastric ulcer, chronic atrophic gastritis) in the general population was 9.27%, and that in the high-risk population was 25.18%. The detection rate of colonic polyps was 53.76% in the general population and 56.77% in the high-risk population. CONCLUSION: Both the high-risk and the general population should consider gastroscopy and colonoscopy as routine physical examination items. Routine gastroscopy is highly recommended for the high-risk population. The general population should pay close attention to their colonoscopy results. The best screening age for both populations is 40 years old and above.

15.
Fish Shellfish Immunol ; 86: 465-473, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30521966

RESUMO

Nervous necrosis virus (NNV) causes viral nervous necrosis (VNN), a disease that leads to almost 100% mortality among larvae and juvenile fish, severely affecting the aquaculture industry. VNN vaccines based on inactivated viruses or virus-like particles (VLPs) are unsuitable for fish fry with immature adaptive immune systems. Here, we applied an anti-NNV strategy based on affinity peptides (AFPs). Three phage display peptide libraries were screened against RBS, the VLP of orange-spotted grouper nervous necrosis virus (OGNNV). From the positive clones, a dodecapeptide with the highest binding capacity (BC) to RBS was selected. This AFP agglutinated or disrupted virion particles, inhibiting RBS entry into sea bass (SB) cells. To enhance BC and solubility, we amended the AFP sequence as "LHWDFQSWVPLL" and named as 12C. One to three copies of 12C in tandem were prokaryotically expressed with a maltose binding protein (MBP) linked by a flexible peptide. Of the recombinant proteins expressed, MBP-triple-12C (MBP-T12C) exhibited the highest BC, efficiently blocked RBS entry, and strongly inhibited OGNNV infection at viral entry. Moreover, MBP-T12C bound the VLPs of all NNV serotypes, displaying broad-spectrum anti-NNV ability, and recognized only OGNNV and mud crab virus, demonstrating binding specificity. Therefore, these anti-NNV AFPs specifically bound NNV, aggregating or disrupting the viral particles, to reduce the contact probability between the virus and cell surface, subsequently inhibiting viral infection. Our results not only provided a candidate of anti-NNV AFP, but a framework for the development of antiviral AFP.


Assuntos
Bass , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Nodaviridae/fisiologia , Peptídeos/imunologia , Infecções por Vírus de RNA/veterinária , Internalização do Vírus , Animais , Antivirais/imunologia , Doenças dos Peixes/virologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/virologia , Proteínas Recombinantes/imunologia
16.
Mol Cell Biol ; 38(12)2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29610151

RESUMO

The pituitary-derived somatolactotrophe GH3 cells secrete both growth hormone (GH) and prolactin (PRL). We have found that the hnRNP L and L-like (LL) paralogs differentially regulate alternative splicing of genes in these cells. Here, we show that hnRNP L is essential for PRL only, but LL is essential for both PRL and GH production. Transcriptome-wide RNA sequencing (RNA-Seq) analysis indicates that they differentially control groups of hormone or hormone-related genes involved in hormone production/regulation at total transcript and alternative exon levels. Interestingly, hnRNP L also specifically binds and prevents the aberrant usage of a nonconserved CA-rich intron piece of Prl pre-mRNA transcripts, and many others involved in endocrine functions, to prevent mostly cryptic last exons and mRNA truncation. Essential for the full hnRNP L effect on specific exons is a proline-rich region that emerged during evolution in vertebrate hnRNP L only but not LL. Together, our data demonstrate that the hnRNP L and its paralog, LL, differentially control hormone gene expression programs at multiple levels, and hnRNP L in particular is critical for protecting the transcriptome from aberrant usage of intronic sequences. The multilevel differential control by hnRNPs likely tailors the transcriptome to help refine and safeguard the different gene expression programs for different hormones.


Assuntos
Regulação da Expressão Gênica/genética , Hormônio do Crescimento/biossíntese , Ribonucleoproteínas Nucleares Heterogêneas Grupo L/genética , Lactotrofos/metabolismo , Prolactina/biossíntese , Somatotrofos/metabolismo , Processamento Alternativo/genética , Sequência de Aminoácidos/genética , Diferenciação Celular/genética , Linhagem Celular , Células HEK293 , Células HeLa , Humanos , Hipófise/citologia , Hipófise/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Transcriptoma/genética
17.
Zhonghua Shao Shang Za Zhi ; 32(6): 326-30, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-27321485

RESUMO

OBJECTIVE: To retrospectively explore the effectiveness of surgical intervention model for repairing the tuberculosis wound with sinus tract. METHODS: Forty-three patients with tuberculosis wound with sinus tract who met the inclusion criteria were admitted to the 309th Hospital of PLA from January 2010 to October 2015. These patients were divided into test group (n=38) and control group (n=5) according to the different treatment and patient's consent. Patients in test group were treated as follows. Firstly, antituberculosis drugs were taken orally for at least 3 weeks, and the wounds were accurately assessed using magnetic resonance imaging combined with 3-dimensional reconstruction software. Then sinus tract and its surrounding devitalized tissue were completely excised, and vacuum sealing drainage (VSD) treatment with negative pressure value of -26.6 kPa was performed for 1 to 2 weeks (dressing change was performed per 7 days). Lastly, the wounds were covered through direct suture or grafting skin or flap. Patients in control group were firstly given antituberculosis drugs orally for at least 3 weeks, and then they were treated with routine dressing change in outpatient service every 3 days. After the former therapy, patients in both groups were given antituberculosis drugs by oral administration for at least 6 months and were followed up for 6 to 36 months. Detection of Bacillus tuberculosis, Acid-fast bacilli, and tuberculosis granuloma, wound healing time, and relapse of tuberculosis wound in patients of both groups were recorded. The rates of single sinus tract, two sinus tracts, and more than or equal to 3 sinus tracts of patients in test group were recorded. Data were processed with Fisher's exact test and Wilcoxon rank-sum test. RESULTS: Bacillus tuberculosis was respectively detected in wounds of 5 patients in test group and 2 patients in control group. Acid-fast bacilli were positively expressed in wounds of 8 patients in test group and 3 patients in control group. A typical tuberculosis granuloma phenomenon was observed in the wounds of 27 patients in test group and 4 patients in control group. These differences in above-mentioned 3 indexes between two groups were not statistically significant (with P values respectively 0.238 4, 0.154 4, 1.000 0). The median of wound healing time of patients in test group was 19.6 d, which was significantly shorter than that in control group (94.4 d, χ(2)=12.986 0, P=0.000 3). There were 2 and 1 patients with recurrent tuberculosis wound in test group and control group respectively, without statistically significant difference (P=0.363 0). Among patients in test group, the rate of single sinus tract was 23.7%(9/38), the rate of two sinus tracts was 28.9%(11/38), and the rate of more than or equal to 3 sinus tracts was 47.4% (18/38). CONCLUSIONS: Repairing the tuberculosis wound with sinus tract in surgical intervention model of antituberculosis therapy+ accurate wound assessment+ debridement+ VSD treatment+ surgical repair is beneficial to making the optimal operation plan under the premise of knowing location of sinus tract, which can reduce surgical risk.


Assuntos
Seios Paranasais/patologia , Transplante de Pele , Retalhos Cirúrgicos , Tuberculose/cirurgia , Cicatrização , Desbridamento , Humanos , Imageamento por Ressonância Magnética , Tratamento de Ferimentos com Pressão Negativa , Seios Paranasais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose/tratamento farmacológico
18.
Oxid Med Cell Longev ; 2015: 186736, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26171113

RESUMO

The aim of the study was to determine whether or not dexmedetomidine- (DEX-) based intravenous infusion in dental implantation can provide better sedation and postoperative analgesia via suppressing postoperative inflammation and oxidative stress. Sixty patients were randomly assigned to receive either DEX (group D) or midazolam (group M). Recorded variables were vital sign (SBP/HR/RPP/SpO2/RR), visual analogue scale (VAS) pain scores, and observer's assessment of alertness/sedation scale (OAAS) scores. The plasma levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), antioxidant superoxide dismutase (SOD), and the lipid peroxidation product malondialdehyde (MDA) were detected at baseline and after 2, 4, and 24 h of drug administration. The VAS pain scores and OAAS scores were significantly lower for patients in group D compared to group M. The plasma levels of TNF-α, IL-6, and MDA were significantly lower in group D patients than those in group M at 2 h and 4 h. In group M, SOD levels decreased as compared to group D at 2 h and 4 h. The plasma levels of TNF-α, IL-6, and MDA were positively correlated with VAS pain scores while SOD negatively correlated with VAS pain scores. Therefore, DEX appears to provide better sedation during office-based artificial tooth implantation. DEX offers better postoperative analgesia via anti-inflammatory and antioxidation pathway.


Assuntos
Analgésicos não Narcóticos/farmacologia , Implantes Dentários , Dexmedetomidina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hipnóticos e Sedativos/farmacologia , Inflamação/prevenção & controle , Interleucina-6/sangue , Masculino , Malondialdeído/sangue , Midazolam/farmacologia , Pessoa de Meia-Idade , Dor/patologia , Complicações Pós-Operatórias/prevenção & controle , Índice de Gravidade de Doença , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangue
19.
Cell Physiol Biochem ; 36(2): 499-508, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25966742

RESUMO

BACKGROUND/AIMS: Treatments targeting cancer stem cells (CSCs) are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined. METHODS: Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and ß-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and ß-catenin were used to inhibit autophagy and ß-catenin signaling pathway, respectively, as loss-of-function experiments. RESULTS: We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced ß-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on ß-catenin and cell viability, while increasing ß-catenin abolished the effects of GRh2 on autophagy and cell viability. CONCLUSION: Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through reduced the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and ß-catenin signaling.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Ginsenosídeos/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , beta Catenina/metabolismo
20.
Int Surg ; 100(1): 155-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25594656

RESUMO

In the current study, we investigated whether anti-CD27 monoclonal antibody can enhance the antitumor efficacy of a dendritic cell-based vaccine in prostate cancer-bearing mice. The overall therapeutic effect of a dendritic cell-based vaccine for prostate cancer remains moderate. A prostate cancer model was established by subcutaneous injection of RM-1 tumor cells into male C57BL/6 mice on day 0. After 4 days, tumor-bearing mice were treated with RM-1 tumor lysate-pulsed dendritic cells (i.e., dendritic cell-based vaccine), anti-CD27 monoclonal antibody, or a combination of RM-1 tumor lysate-pulsed dendritic cells with anti-CD27 monoclonal antibody. Mice were killed at 21 days after tumor cell implantation. Tumor size was measured for assessment of antitumor effect. Spleens were collected for analysis of antitumor immune responses. The antitumor immune responses were evaluated by measuring the proliferation and activity of T cells, which have the ability to kill tumor cells. The combination therapy with RM-1 tumor lysate-pulsed dendritic cells and anti-CD27 antibody significantly enhanced T-cell proliferation and activity, and significantly reduced tumor growth, compared with monotherapy with RM-1 tumor lysate-pulsed dendritic cells or anti-CD27 antibody. Our results suggest that combined treatment can strengthen antitumor efficacy by improving T-cell proliferation and activity.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Células Dendríticas/imunologia , Neoplasias da Próstata/prevenção & controle , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Animais , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Terapia Combinada , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Distribuição Aleatória , Resultado do Tratamento
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