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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117450, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31422341

RESUMO

Laser-induced fluorescence (LIF) is an effective technique for non-intrusive and on-line measurement of PAHs in sooting flames but it is still need further investigation due to the complexity of PAH fluorescence characteristics. Therefore, in-depth investigations on the fluorescence spectroscopy of PAHs with different molecular structures are relevant. In this study, we investigated the fluorescence spectrum characteristics of 13 gas-phase PAHs using LIF measurement and time-dependent density functional theory (TD-DFT) calculation. The experimental results showed that the fluorescence emission wavelengths increased with more aromatic (benzenoid) rings, but this relationship no longer existed when the PAH molecules contain the five-membered ring structures. The TD-DFT calculation showed that the fluorescence emission wavelength ranges of PAHs with different molecular structures were dominantly determined by the electronic structures of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and their energy gaps. It was found that the saturated aliphatic branched chains (methyl and ethyl) only slightly influenced the LIF spectra, while the unsaturated aliphatic branched chains (ethenyl and ethynyl) caused remarkable redshifts. The TD-DFT results indicated that the aliphatic branched chains changed the electric structures of HOMO and LUMO of the core aromatic rings, and then influence the fluorescence emission wavelength ranges.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31721430

RESUMO

OBJECTIVES: We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD. BACKGROUND: Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI. METHODS: Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208. RESULTS: Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p < .001). HD was associated with increased 2-year rates of MACE (death, myocardial infarction (MI) or definite stent thrombosis (ST); 23.4% vs. 10.7%, p < .001). HD was also strongly associated with 2-year overall mortality, cardiac death, MI, target vessel revascularization, major bleeding, stroke and ST. Following adjustment for HPR and other covariates, HD was independently associated with overall mortality, MI, ST, and major bleeding at 2 years. The relationship between HD status and 2-year MACE was consistent in patients with and without HPR (Pinteraction = .78). CONCLUSIONS: Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR.

3.
ACS Sens ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31701738

RESUMO

Selenocysteine (Sec), a vital member of reactive selenium species, is closely implicated in diverse pathophysiological states, including cancer, cardiovascular diseases, diabetes, neurodegenerative diseases, and male infertility. Monitoring Sec in vivo is of significant interest for understanding the physiological roles of Sec and the mechanisms of human diseases associated with abnormal levels of Sec. However, no bioluminescence probe for real-time monitoring of Sec in vivo has been reported. Herein, we present a novel bioluminescent probe BF-1 as an effective tool for the determination of Sec in living cells and in vivo for the first time. BF-1 has advantages of high sensitivity (a detection limit of 8 nM), remarkable bioluminescence enhancement (580-fold), reasonable selectivity, low cytotoxicity, and high signal-to-noise ratio imaging feasibility of Sec in living cells and mice. More importantly, BF-1 affords high sensitivity for monitoring Sec stimulated by Na2SeO3 in tumor-bearing mice. These results demonstrate that our new probe could serve as a powerful tool to selectively monitor Sec in vivo, thus providing a valuable approach for exploring the physiological and pathological functions and anticancer mechanisms of selenium.

4.
Virol J ; 16(1): 135, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718675

RESUMO

BACKGROUND: H9N2 influenza viruses continuously circulate in multiple avian species and are repeatedly transmitted to humans, posing a significant threat to public health. To investigate the adaptation ability of H9N2 avian influenza viruses (AIVs) to mammals and the mutations related to the host switch events, we serially passaged in mice two H9N2 viruses of different HA lineages - A/Quail/Hong Kong/G1/97 (G1) of the G1-like lineage and A/chicken/Shandong/ZB/2007 (ZB) of the BJ/94-like lineage -and generated two mouse-adapted H9N2 viruses (G1-MA and ZB-MA) that possessed significantly higher virulence than the wide-type viruses. FINDING: ZB-MA replicated systemically in mice. Genomic sequence alignment revealed 10 amino acid mutations coded by 4 different gene segments (PB2, PA, HA, and M) in G1-MA compared with the G1 virus and 23 amino acid mutations in 5 gene segments (PB1, PA, HA, M, and NS) in ZB-MA compared to ZB virus, indicating that the mutations in the polymerase, HA, M, and NS genes play critical roles in the adaptation of H9N2 AIVs to mammals, especially, the mutations of M1-Q198H and M1-A239T were shared in G1-MA and ZB-MA viruses. Additionally, several substitutions showed a higher frequency in human influenza viruses compared with avian viruses. CONCLUSIONS: Different lineages of H9N2 could adapt well in mice and some viruses could gain the ability to replicate systemically and become neurovirulent. Thus, it is essential to pay attention to the mammalian adaptive evolution of the H9N2 virus.

5.
Am J Transplant ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31652392

RESUMO

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants.

6.
Clin Interv Aging ; 14: 1693-1703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631990

RESUMO

Purpose: Define the effectiveness of teriparatide (TPTD) treatment on reducing the incidence of new vertebral compression fractures (NVCFs) and back pain and improving quality of life after percutaneous kyphoplasty (PKP). Methods: Two years of clinical follow-up data from primary osteoporotic women who had experienced initial osteoporotic vertebral compression fractures (OVCFs) and received PKP plus 12-month TPTD (n=113) or basic treatment (BT) of calcium and vitamin D supplements (n=208) were retrospectively collected. The risk of NVCFs over each 6-month period in the TPTD group was evaluated and compared with the BT group using a logistic regression. Health-related quality of life (HRQoL, EQ-5D questionnaire), back pain [100 mm visual analog scale (VAS)] and bone mineral density (BMD) of the spine were analyzed using linear mixed models for repeated measures (LMMRM). Results: Logistic regression analysis adjusting for baseline characteristics showed that patients in the TPTD group had a lower risk of NVCFs compared with those receiving BT during the final three observation intervals (6-12 months, OR=0.189, 95% CI=0.030-0.681, p=0.046; 12-18 months, OR=0.009, 95% CI=0.0001-0.111, p=0.001; 18-24 months, OR=0.024, 95% CI=0.0009-0.264, p=0.009, respectively). Significant improvements in adjusted EQ-5D and back pain VAS scores were identified in the TPTD group compared with the BT group, and this improvement was sustained for at least 12 months after teriparatide treatment was discontinued (both p<0.001). The BMD of the spine also showed a higher T-value in the TPTD group compared with the BT group (p<0.001). Conclusion: In routine clinical practice, for patients with OVCFs who receive the PKP procedure, TPTD treatment may be a preferable subsequent therapy because of its ability to reduce the incidence of NVCFs and sustain a high quality of life and back pain alleviation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31620778

RESUMO

OBJECTIVES: The SYNTAX score II (SSII) was developed from the SYNTAX trial to predict the 4-year all-cause mortality after left main or multivessel disease revascularization and to facilitate the decision-making process. The SSII provides the following treatment recommendations: (i) coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (equipoise risk), (ii) CABG preferred (excessive risk for PCI) or (iii) PCI preferred (excessive risk for CABG). We sought to externally validate SSII and to investigate the impact of not abiding by the SSII recommendations in the randomized EXCEL trial of PCI versus CABG for left main disease. METHODS: The calibration plot of predicted versus observed 4-year mortality was constructed from individual values of SSII in EXCEL. To assess overestimation versus underestimation of predicted mortality risk, an optimal fit regression line with slope and intercept was determined. Prospective treatment recommendations based on SSII were compared with actual treatments and all-cause mortality at 4 years. RESULTS: SSII variables were available from EXCEL trial in 1807/1905 (95%) patients. For the entire cohort, discrimination was possibly helpful (C statistic = 0.670). SSII-predicted all-cause mortality at 4 years overestimated the observed mortality, particularly in the highest-risk percentiles, as confirmed by the fit regression line [intercept 2.37 (1.51-3.24), P = 0.003; slope 0.67 (0.61-0.74), P < 0.001]. When the SSII-recommended treatment was CABG, randomized EXCEL patients treated with PCI had a trend towards higher mortality compared with those treated with CABG (14.1% vs 5.3%, P = 0.07) in the as-treat population. In the intention-to-treat population, patients randomized to PCI had higher mortality compared with those randomized to CABG (15.1% vs 4.1%, P = 0.02), when SSII recommended CABG. CONCLUSIONS: In the EXCEL trial of patients with left main disease, the SSII-predicted 4-year mortality overestimated the 4-year observed mortality with a possibly helpful discrimination. Non-compliance with SSII CABG treatment recommendations (i.e. randomized to PCI) was associated with higher 4-year all-cause mortality.

8.
Small ; : e1904979, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659867

RESUMO

Drug-eluting stents (DESs) are promising candidates for treating human oesophageal cancer. However, the use of DESs to assist photodynamic therapy (PDT) of orthotopic oesophageal tumors is not yet demonstrated to the best of current knowledge. Herein, through an electrospinning technology it is shown that oxygen-producing manganese dioxide nanoparticles are embedded into elelctrospun fibers, which are subsequently covered onto stents. Upon implantation, the nanoparticles are gradually released from the fibers and then diffuse into the nearby tumor tissue. Then, the hypoxic microenvironment can be effectively alleviated by reaction of MnO2 with the endogenous H2 O2 within the tumor. After demonstrating the excellent PDT efficacy of the stents in a conventional subcutaneous mouse tumor model, such stents are further used for PDT treatment in a rabbit orthotopic oesophageal cancer model by inserting an optical fiber into the tumor site. Greatly prolonged survival of rabbits is observed after such intraluminal PDT treatment. Taken together, this work shows that the fiber-covered stent as a nanoparticle delivery platform can enable effective PDT as a noninvasive treatment method for patients with advanced-stage oesophageal cancer.

9.
Acta Biomater ; 94: 295-305, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31195144

RESUMO

Aneurysmal subarachnoid hemorrhage (SAH) causes high rates of mortality and morbidity. A covered stent is an effective endovascular treatment for complicated aneurysms intractable to endovascular coiling and surgical clipping. However, in-stent restenosis and delayed endothelialization are the main challenges contributing to its safety. In this study, we designed a biofunctional stent covered with dual drug-loaded electrospun fibers to achieve programmed vascular endothelial growth factor (VEGF) and paclitaxel (PTX) release for the early promotion of stent endothelialization and long-term inhibition of stenosis caused by smooth muscle hyperplasia. By encapsulating PTX-loaded mesoporous silica nanoparticles (MSNs) within electrospun polylactic acid (PLA) fibers, the release period of PTX was effectively extended. Furthermore, VEGF was conjugated onto the surface of the membrane by reacting with polydopamine (PDA) for quick release. The in vitro drug release profile revealed the sustained release of PTX, which persisted for 63 days without early burst release, while up to 87.05% of VEGF was rapidly released within 3 days. After 6 days of incubation, cell experiments demonstrated that the dual drug-loaded scaffold effectively prompted endothelial cell proliferation (488% vs. 386% in the control group, P = 0.001) and inhibited the proliferation of smooth muscle cells (SMCs) using the 21-day extracts (155% vs. 303% in the control group, P = 0.039). Animal studies showed that compared to bare stents, the drug-loaded covered stents improved the immediate- and mid-term complete aneurysm occlusion rates (P < 0.05). The drug-loaded covered stents also showed earlier endothelialization promotion and better lumen restenosis than normal covered stents (0% vs. 25%, P = 0.29) for 12 weeks. Overall, a programmed dual drug-loaded scaffold that effectively occluded the aneurysm sac was developed in this study, and the discrete release of VEGF and PTX promoted endothelialization and prevented in-stent stenosis. This study provided a new method to improve the biosafety of implanted covered stents for the treatment of intracranial aneurysms. STATEMENT OF SIGNIFICANCE: Aneurysmal subarachnoid hemorrhage (SAH) is one of the most common hemorrhage stroke resulted in a nearly 40% mortality and 33% morbidity due to sudden rupture of an intracranial aneurysm. Endovascular coil embolism is a popular treatment for aneurysm but this technique run high risk of bleeding, mass effect, low complete occlusion rate and higher recanalization rate due to its operation conducted within aneurysm sac. A bio-functional membrane knitted by dual-drug loaded electrospun fibers covered on a stent was designed to realize programed vascular endothelial growth factor and paclitaxel release for the early promotion of vascular endothelium and long-term inhibition of stenosis caused by smooth muscle hyperplasia. This study provides new method to improve the biosafety of covered stent insertion for the treatment of intracranial aneurysms.

10.
Am Heart J ; 214: 9-17, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31150791

RESUMO

BACKGROUND: Prompt revascularization is often required in acute coronary syndromes (ACS), whereas stable ischemic heart disease (SIHD) may allow for more measured procedural planning. Whether the acuity of presentation preferentially affects outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with left main coronary artery disease (LMCAD) is unknown. We investigated whether the acuity of presentation discriminated patients who derived a differential benefit from PCI versus CABG in the randomized Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial. METHODS: We used multivariable Cox models to assess the interaction between the acuity of presentation, type of revascularization and outcomes in patients with low or intermediate SYNTAX scores enrolled in EXCEL. RESULTS: At baseline, 1151 patients (60.7%) presented with SIHD and 746 patients (39.3%) presented with an ACS. The acuity of presentation was not associated with the primary endpoint of all-cause death, MI, or stroke at 3 years (multivariable adjusted hazard ratio [HR] 0.94; 95% CI 0.70-1.26, P = .64). The primary endpoint rate was similar in patients assigned to PCI versus CABG whether they presented with SIHD (adjusted HR 1.04; 95% CI 0.73-1.48]) or with ACS (HR 0.82; 95% CI 0.54-1.26) (Pinteraction = .34). CONCLUSIONS: The acuity of presentation did not predict outcomes in patients with LMCAD undergoing revascularization, nor did it discriminate patients who derive greater event-free survival from PCI versus CABG.

11.
FEBS Lett ; 593(11): 1248-1256, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31049949

RESUMO

To date, few structural models of VHH antibody binding to low molecular weight haptens have been reported. Here, we report the crystal structure of cortisol binding to its VHH antibody NbCor at pH 3.5 and 10.5. Cortisol binds to NbCor mainly by burying itself under the tunnel formed by the complementarity determining region 1 (CDR1) of NbCor. The affinity of NbCor binding to cortisol and similar compounds was also verified by a microscale thermophoresis assay. Combining our findings with several previously reported structures of hapten-VHH antibody complexes, we propose that VHH antibodies exhibit a special mechanism of binding small haptens by encapsulating them in a tunnel formed by CDR1. Our findings provide useful structural information for the further development and optimization of hapten-specific VHH antibodies.

13.
Prog Mol Biol Transl Sci ; 163: 165-177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31030747

RESUMO

Ganoderma sinense is one of well-known herb medicine and has been used for 2000 years in China. G. lucidum and G. sinense are two family members of Ganoderma, a genus of polypore fungi. In Chinese, "Lingzhi" is designated as G. lucidum or red "Lingzhi" whereas "Zizhi" as G. sinense or purple "Lingzhi." The polysaccharides or glycans extracted from both G. lucidum and G. sinense have been developed into clinical drugs and recorded in Chinese Pharmacopeia. G. lucidum polysaccharide (GLPS) is one of a few non-hormonal drugs used for treating neurosis, polymyositis, dermatomyositis, atrophic myotonia and muscular dystrophy in China during the past 40 years. In contrast, G. sinense polysaccharide (GSP) tablet is approved as an adjunctive therapeutic drug in China for treating leukopenia and hematopoietic injury caused by concurrent chemo/radiation therapy during cancer treatment by the State Food and Drug Administration (SFDA) in 2010. ß-glucan, an established immunostimulanting polysaccharide, is one of the components in GSP. In this study, we will review the biological activities and preclinical studies of GSP in China based on literatures searches from CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database), Wanfang database, and PubMed database. Both basic and preclinical studies showed that GSP has antitumor, antioxidant, anticytopenia, and unique mushroom-poison detoxification properties that are different from that of GLPS. Our goal is to provide a molecular picture that would allow in-depth evaluation of GSP as one of few glycan-based drugs that has been used as an immunomodulatory adjunctive drug during cancer therapy.

14.
Prog Mol Biol Transl Sci ; 163: 297-328, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31030752

RESUMO

Lentinula edodes has been used to improve general health for thousands of years in Asia. It is the second largest cultivated and the most popular edible mushroom in the world known as "Xianggu" in China and "Shiitake" in Japan. Lentinan is a polysaccharide extracted from Lentinula edodes. ß-Glucan is the major bioactive component in lentinan with immunostimulatory effect. The antitumor property of lentinan was reported in 1960s. Biochemical studies indicate that immunocytes can be activated by lentinan through multiple signaling pathways, such as TLR4/Dectin1-MAPK and Syk-PKC-NFκB pathways. Though it has been approved as an adjuvant therapeutic drug both in China and Japan for treating cancers since 1980s, a systematic review of clinical studies of lentinan has not been conducted elaborately. In this review, over 9474 reported lentinan-associated cancer treatment cases are evaluated and summarized from 135 independent studies in China during the past 12 years (2004-2016) based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database) and Wanfang database. The 9474 reported lentinan-associated cancer treatment cases include lung cancer (3469 cases), gastric cancer (3039 cases), colorectal cancer (1646 cases), ovarian cancer (183 cases), cervical cancer (130 cases), Non-Hodgkin lymphoma (70 cases), pancreatic cancer (15 cases), cardiac cancer (15 cases), nasopharyngeal cancer (14 cases), duodenal cancer (1 case) and 110 cancer cases with no classifying patient information. Overall clinical data show solid effect of lentinan on improving the quality of life and on promoting the efficacy of chemotherapy and radiation therapy during cancer treatment.

15.
Prog Mol Biol Transl Sci ; 163: 41-53, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31030756

RESUMO

Fondaparinux is a synthetic heparin pentasaccharide with a sequence identical to that found in anticoagulant heparin. It is a pure compound with a molecular weight of 1728Da. Fondaparinux catalyzes the conformational change of a serpin or serine protease inhibitor antithrombin III to accelerate the suicidal inactivation of factor Xa over 340-fold, which in turn inhibits thrombin generation in the coagulating signal transduction pathway. Fondaparinux does not inhibit thrombin activity, release tissue factor pathway inhibitor, or possess other properties of heparin such as anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, and anti-metastatic effects though high affinity interactions with a variety of proteases, protease inhibitors, chemokines, cytokines, growth factors, and their respective receptors. Low antithrombin III levels in blood circulation also affects the efficacy of Fondaparinux. Thus, Fondaparinux represents a refined use of the anti-factor Xa property of heparin. As an anti-factor Xa drug, Fondaparinux has complete bioavailability subcutaneously, instant onset of action, a half-life of 15-20h, and a direct renal excretion without any metabolism. Fondaparinux has been shown to be superior to low molecular weight heparin in preventing deep vein thrombosis. Clinically, Fondaparinux is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism with limitations of use in elderly, low weight, renal impaired patients and in those receiving spinal anesthesia. Clinical studies showed that Fondaparinux acts in prevention and treatment of venous thromboembolism and in ischemic heart disease without significant risk of bleeding.

16.
Prog Mol Biol Transl Sci ; 163: 471-485, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31030759

RESUMO

The therapeutic market for monoclonal antibodies (MAbs) has grown exponentially since 2000. It is expected that the world-wide market for MAbs could reach $125 billion in 2020. For cancer treatment alone, more than 30 MAbs have been approved by the US Food and Drug Administration since 1997. Unlike structure-defined small molecule-based anti-cancer drugs, the expensive MAb is a mixture of heterogeneously glycosylated proteins. All MAbs typically have a single N-glycosylation site on each of the Fc region. The clinical efficacy of the MAbs depends on the N-glycan structures. Loss of N-glycosylation on the MAbs leads to the loss of the ability to activate complement, to bind to Fc receptors, and to induce antibody-dependent cellular cytotoxicity (ADCC). Moreover, antigen-antibody complexes produced from N-glycan-deficient MAbs are failed to be eliminated rapidly from the blood circulation. Even in certain cases, the N-glycan heterogeneity does not significantly influence pharmacokinetics or half-life of MAbs, reduced terminal galactosylation decreases complement-dependent cytotoxicity, the absence of core fucosylation enhances ADCC due to the increased affinities for the FcγRIIIа receptor, and high sialylation levels reduce ADCC activity and impact inflammatory responses. Furthermore, only mammalian cell lines that make human-like N-glycan structures can be used for MAbs production since certain mammalian cell lines can produce non-human glycan epitopes such as galactose-α-1,3-galactose and N-glycolylneuraminic acid (NGNA), which can trigger unwanted immune response. Therefore, mastering the knowledge of N-glycan structures and glycobiology is the key to produce and provide patients with reliable MAbs with consistent glycosylation profile and expected clinical efficacy.

17.
Sensors (Basel) ; 19(6)2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30909468

RESUMO

An accurate prediction of cage-cultured water quality is a hot topic in smart mariculture. Since the mariculturing environment is always open to its surroundings, the changes in water quality parameters are normally nonlinear, dynamic, changeable, and complex. However, traditional forecasting methods have lots of problems, such as low accuracy, poor generalization, and high time complexity. In order to solve these shortcomings, a novel water quality prediction method based on the deep LSTM (long short-term memory) learning network is proposed to predict pH and water temperature. Firstly, linear interpolation, smoothing, and moving average filtering techniques are used to repair, correct, and de-noise water quality data, respectively. Secondly, Pearson's correlation coefficient is used to obtain the correlation priors between pH, water temperature, and other water quality parameters. Finally, a water quality prediction model based on LSTM is constructed using the preprocessed data and its correlation information. Experimental results show that, in the short-term prediction, the prediction accuracy of pH and water temperature can reach 98.56% and 98.97%, and the time cost of the predictions is 0.273 s and 0.257 s, respectively. In the long-term prediction, the prediction accuracy of pH and water temperature can reach 95.76% and 96.88%, respectively.

18.
Prog Mol Biol Transl Sci ; 162: 141-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30905446

RESUMO

Most of clinically used cancer biomarkers are either specific glycan structures or glycoproteins. Although the high serum levels of the cancer biomarkers are also present in certain patients suffering noncancer diseases, systematic measurement and comparison of the serum levels of all cancer biomarkers among cancer and noncancer patients have not been reported. In this study, the serum levels of 17 glucose and glycan-related biomarkers including 10 cancer biomarkers SCCA, CA724, CA50, CA242, CA125, CA199, CA153, AFP, CEA, and PSA were retrospectively investigated based on clinical laboratory data in two medical centers during the past 6 years (2012-2018). The data included a total of 1,477,309 clinical lab test results of 17 biomarkers from healthy controls and patients suffering 64 different types of cancer and noncancer diseases. We found that the median serum levels of CA724, CEA, CA153, SCCA, and CA125 were highest not in cancer patients but in patients suffering gout, lung fibrosis, nephrotic syndrome, uremia, and cirrhosis, respectively. Consistently, the classical ovarian cancer biomarker CA125 had better overall sensitivity and specificity as biomarker for cirrhosis (67% and 92%, respectively) than that for ovarian cancer (41% and 97%, respectively). Furthermore, the information shown as heatmap or waterfall built on the -Log10p values of the 17 glycan-related biomarkers in different clinically defined diseases suggested that all glycan-related biomarkers had cancer-, aging-, and disease-relevant characteristics and cancers were systems disease. The detailed presentation of the data for each of the 17 biomarkers will be deliberated in chapters 6-23 in this book series.

19.
Prog Mol Biol Transl Sci ; 162: 177-186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30905448

RESUMO

CA724 is a clinically used serum biomarker used for cancer diagnosis, which includes digestive tract cancers (esophageal, gastric, and colorectal carcinomas), ovarian cancer, and nonsmall cell lung cancer. In general, the serum CA724 level is lower than 6U/mL in healthy controls and significantly higher in cancer patients. It has been further established that serum CA724 level is related to the pathological stage and prognosis of cancers. However, CA724 is not only expressed in tumor tissues but also in normal tissues such as the secretory endometrium and transitional colonic mucosa, which indicates that CA724 is not a unique product of cancer cells. Currently, the serum CA724 levels in patients suffering cancer or nonneoplasm diseases have not been systematically measured and compared. In our study, a total of 38,526 clinical lab test results of serum CA724 levels from healthy controls and patients suffering 34 different types of diseases including cancers and nonneoplasm illnesses during the past 3 years (2015-2018) were collected and analyzed. We found that the mean values of serum CA724 levels were significantly higher in patients suffering gout (23.7U/mL) and gouty arthritis (31.45U/mL) than that of cancer patients (Mann-Whitney test, p<0.0001). The summarized mean and median values of serum CA724 data for healthy controls vs patients suffering 34 different types of diseases indicated that the abnormal serum CA724 levels might be a systemic malfunction indicator rather than a cancer cell-secreted product; the log10p values showed that CA724 is not only a cancer biomarker but also a potential biomarker for patients suffering gout.

20.
Prog Mol Biol Transl Sci ; 162: 241-252, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30905453

RESUMO

CA125 is a heavily glycosylated protein and was first identified as an ovarian cancer antigen in 1981 that is recognized by a monoclonal antibody generated by the hybridoma technique. The increased serum CA125 levels detected by the monoclonal antibodies were subsequently developed into a diagnostic or prognostic biomarker for ovarian cancer. Generally, the cutoff value of serum CA125 level is 35U/mL to indicate potential cancer risk. However, the specificity and sensitivity of CA125 are not satisfactory in clinical applications, especially for early diagnosis of ovarian cancer. Moreover, elevated serum CA125 levels have been observed in a variety of cancer and noncancer diseases. In the current study, a total of 41,830 clinical lab test results of serum CA125 levels from healthy individuals and patients with 40 different types of diseases during the past 5 years were retrieved and analyzed. We found that the median values of serum CA125 levels were higher in patients with cirrhosis (52.34U/mL), lung fibrosis (52.04U/mL), nephrotic syndrome (31.24U/mL), and pancreatic cancer (27.06U/mL) than that in ovarian cancer patients (18.61U/mL) with statistical significance (Mann-Whitney test, p<0.0001). Moreover, healthy individuals >65 years old and patients suffering rectal cancer, cerebrovascular disease, and gastritis had significantly low serum CA125 levels compared to that of the healthy individuals. Thus, serum CA125 levels were either increased or decreased in both cancer and noncancer diseases. Based on these data and the accumulating evidence, we proposed that the abnormal serum CA125 levels might be associated with pathological changes in different organs and tissues induced by specific disease.

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