Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.837
Filtrar
1.
Mol Cell Biochem ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33389499

RESUMO

SARS-CoV-2 is one of the beta-coronaviruses with the spike protein. It invades host cells by binding to angiotensin converting enzyme 2 (ACE2). This newly discovered virus can result in excessive inflammation and immune pathological damage, as shown by a decreased number of peripheral lymphocytes, increased levels of cytokines, and damages of lung, heart, liver, kidney, and other organs. Effective therapeutic modalities such as new antiviral drugs and vaccines against this emerging virus need to be thoroughly studied and developed. However, so far the only recognized but mild progress in this area is the screening of old drugs for new uses. Therefore, rapid and accurate laboratory SARS-CoV-2 testing approaches are the important basis of identification and blockage of COVID-19 transmission. For COVID-19 patients with different clinical classifications (mild, common, severe, and critically severe), dynamic monitoring of functional indicators of susceptible and vital organs is an important strategy for evaluating therapeutic efficacy and prognosis. In this review, we summarized SARS-CoV-2 laboratory diagnostic schemes, pathophysiological indices of tissues and organs of COVID-19 patients, and laboratory diagnostic strategies for distinct disease stages. Further, we discussed the importance of hierarchical management and dynamic observation in SARS-CoV-2 laboratory diagnostics. We then summed up the advance in SARS-CoV-2 testing technology and described the prospect of intelligent medicine in the prevention of infectious disease outbreaks.

2.
Org Lett ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400542

RESUMO

A regio- and stereoselective nickel-catalyzed three-component coupling reaction of aldehydes, 1,3-dienes, and alkenylzirconium reagents was realized. The ligand- and additive-free protocol afforded a convenient approach to the synthesis of skipped diene compounds bearing various functionals (e.g., hydroxyl, carbonyl, halide) and heterocyclic groups. The products were readily transformed into structurally diverse polyenes. The utility of this reaction was also demonstrated by the one-pot operation and scale-up preparation.

3.
ChemSusChem ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33403787

RESUMO

The atmospheric CO 2 concentration continues a rapid rise to its current record high value of 416 ppm for the time being. It calls for advanced CO 2 capture technologies. One of the attractive technologies is physical adsorption-based separation, which shows easy regeneration and long cycle stability, and thus reduced energy penalties and cost. The extensive research on this topic is evidenced by the growing body of scientific and technical literature. The progress spans from the innovation of novel porous adsorbents to practical separation practices. Major CO 2 capture materials include the most widely-used industrially relevant porous carbons, zeolites, activated alumina, mesoporous silica, and the newly emerging metal-organic frameworks (MOFs) and covalent-organic framework (COFs), etc. The key intrinsic properties such as pore structure, surface chemistry, preferable adsorption sites and other structural features that would affect CO 2 capture capacity, selectivity, and recyclability are first discussed. The industrial relevant variables such as particle size of adsorbents, the mechanical strength, adsorption heat management and other technological advances are equally important, even more crucial when scaling up from bench and pilot-scale to demonstration and commercial scale. Therefore, we aim to bring a full picture of the adsorption-based CO 2 separation technologies, from adsorbent design, intrinsic properties evaluation to performance assessment not only under the ideal equilibrium conditions but also in realistic pressure swing adsorption processes .

4.
Artigo em Inglês | MEDLINE | ID: mdl-33405172

RESUMO

High dust concentration produced in the fully mechanized longwall mining face is a significant threat to the front-line workers. It is critical to discover the potential safety zone to ensure routine personnel operation. Fluent 2020 R1 is employed to reappear the spatial dust distribution based on the gas-solid coupling theory. The dust migration behavior and safety regional division are illuminated in the spatial longwall mining face. The formation of dust concentration trigonum is introduced with the particle diffusion force analyzed. The YZ plane safety zone area shows an increasing trend at X = 70-95 m. The respirable dust concentration decreases from the peak value to the safe value at sidewalk 4.0-4.6 m. The safety zone area and length both pose a linear growth with the increasing wind velocity. In the XY plane, the safety zone area and length extend by 1.26 times and 1.33 times, respectively. The horizontal plane creates a greater growth rate of safety zone than the vertical plane. The drum rotation creates a wind circumfluence that exerts an obvious effect on the dust distribution around the coal cutter. The sidewalk region mainly situates in the safety zone for the personal squat down, while it is gradually exposed to the dangerous dust pollution situation as the breathing height rises.

5.
Int J Med Sci ; 18(1): 176-186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390786

RESUMO

Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge. Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients' liver function. Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition (P<0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group (P<0.05, and P<0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge (P<0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period. Conclusions: Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized.


Assuntos
/complicações , Insuficiência Hepática/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Lactente , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Adulto Jovem
6.
Int J Med Sci ; 18(2): 347-355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390803

RESUMO

Objectives: Research on recovering COVID-19 patients could be helpful for containing the pandemic and developing vaccines, but we still do not know much about the clinical features, recovery process, and antibody reactions during the recovery period. Methods: We retrospectively analysed the epidemiological information, discharge summaries, and laboratory results of 324 patients. Results: In all, 15 (8.62%) patients experienced chest distress/breath shortness, where 8 of the 15 were severely ill. This means severely ill patients need an extended amount of time to recover after discharge; next, 20 (11.49%) patients experienced anxiety and 21 (12.07%) had headache/insomnia and a small fraction of them complained of anosmia/ageusia, indicating that these patients need treatment for mental and psychological health issues. Regarding the re-positive patients, their CT and laboratory test results showed no obvious evidence of illness progress or infectivity but a high anti-SARS-CoV-2 antibody expression. Conclusion: Recovered COVID-19 patients need psychological and physiological care and treatment, re-positivity can occur in any person, but juveniles, females, and patients with mild/moderate existing symptoms have higher rates of re-positivity, While there is no evidence that turning re-positive has an impact on their infectivity, but it still alerted us that we need differentiate them in the following managements.


Assuntos
/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ageusia , /reabilitação , Criança , Pré-Escolar , China/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Adulto Jovem
7.
Neurol Sci ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411193

RESUMO

OBJECTIVE: Sighing is a common symptom in children and adolescents. In this study, we explored the clinical characteristics and hemodynamic responses to head-up tilt test (HUTT) in children and adolescents with unexplained sighing. METHODS: One hundred ninety-two children and adolescents complaining of unexplained sighing were enrolled as study group after excluding chest wall, lung, heart diseases, and psychogenic disorders. Sixty-nine healthy individuals were enrolled as control group. All the subjects underwent HUTT. RESULTS: Nitroglycerin-stimulated HUTT positive rate was higher in the study group than the control group (24.0% vs 10.1%, P = 0.014). In total, 32.3% of patients with sighing had positive responses to HUTT, which was higher than that of healthy individuals (32.3% vs 15.9%, P = 0.009). Among 62 cases with positive responses to HUTT in the study group, 48 cases were vasoinhibitory type vasovagal syncope (VVS), 5 cases were mixed type VVS, 3 cases were cardioinhibitory type VVS, 5 cases were postural tachycardia syndrome, and one case was orthostatic hypertension. Sighing patients with positive responses to HUTT had female dominance (54.8% vs39.2%, P = 0.045), older mean age (9.6 ± 2.8 vs 8.1 ± 2.7 years old, P = 0.001), higher basic systolic blood pressure (104.8 ± 10.4 vs 101.1 ± 9.9 mmHg, P = 0.019), and higher diastolic blood pressure (66.0 ± 7.5 vs 62.9 ± 9.2 mmHg, P = 0.021) compared with those of negative responses. CONCLUSIONS : Nearly one-third of children and adolescents with unexplained sighing had positive responses to HUTT, demonstrating that sighing was related to dysfunction of the autonomic nervous system. Elder female patients with higher systolic and diastolic blood pressure were more likely to have positive responses to HUTT.

8.
BMC Pregnancy Childbirth ; 21(1): 19, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407234

RESUMO

BACKGROUND: Many maternal factors are known to be associated with adverse birth outcomes, but studies about paternal factors yielded inconsistent conclusions. The study was to assess whether paternal factors are associated with low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA). METHODS: A birth cohort study was conducted in 2010-2012 at the Gansu Provincial Maternity and Child Care Hospital, the largest maternity and childcare hospital in Lanzhou, China. Paternal age, ethnicity, educational level, height, weight, smoking, and drinking were collected. Birth outcomes and pregnancy complications were extracted from the medical records. RESULTS: During the study period, 10,121 participants were included; the overall prevalence of LBW, PTB, and SGA was 7.2, 9.9, and 7.8%, respectively. Paternal higher height (OR = 0.64 95%CI: 0.49, 0.83), higher weight (P for trend < 0.001), and higher BMI (P for trend < 0.001) could decrease the rate of LBW. Paternal higher education (OR = 0.55, 95%CI: 0.43, 0.71) and higher weight (P for trend < 0.001,) were associated with lower rate of PTB. Fathers who smoked more than 6 pack-years were associated with PTB (OR = 1.31, 95%CI: 1.07, 1.61). Paternal BMI > 23.9 kg/m2 (P for trend < 0.001,) and paternal education which above college (OR = 0.61, 95%CI: 0.50, 0.82) were associated with a lower rate of SGA. CONCLUSION: Paternal low education is independently associated with PTB and SGA. Paternal heavy smoking is associated with PTB. Low paternal weight/BMI is independently associated with LBW, PTB, and SGA.

9.
Cell Stem Cell ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33450186

RESUMO

ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human-induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes. ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection. Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes. These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk factors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in different patient populations.

10.
J Neurosci Methods ; : 109075, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33450332

RESUMO

BACKGROUND: To construct a new and improved model of acute subdural hematoma in rats. NEW METHOD: 30 male adult Sprague-Dawley rats(SD rats) were selected and randomly divided into two groups. The traditional model group was based on Miller's model construction method, and the improved model group was based on improved needle, injection site and operation method. The improved model was evaluated by comparing the physiological indicators, behavioral scores, magnetic resonance performance and HE staining results of the two groups of rats. RESULTS: The physical signs of the rats in the two groups were similar. The survival rate of the improved group was higher than that of the traditional group. The hematoma in the improved model was thicker and concentrated in the ipsilateral side, as revealed by HE staining and MRI. The improved method has less intrusions on the cortex around the injection site and is more stable than the traditional model. COMPARISON WITH EXISTING METHOD(S): The operation difficulty of the improved model is reduced and easier. The survival rate of the improved group was higher than that of the traditional group. And the improved model will have more research possibilities. CONCLUSION: The improved model is based on the traditional model. Although it has some shortcomings, it can also be used in different research fields of the traditional model. The operation for the improved model is easier to perform. And the improved model has more applications in research.

11.
Bioresour Technol ; 324: 124662, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33434874

RESUMO

Anaerobic wastewater treatment process is efficient but unstable due to various disturbances, such as refractory organics and influent organic overloading. Therefore, sensitive and accurate status diagnosis is important for reasonable control to improve the stability of anaerobic process. In this study, an online intelligent expert diagnosis system for anaerobic process was established based on moving average convergence and divergence (MACD) indexes of gas- and liquid-phase parameters, combined with online monitoring system and expert diagnosis database. The effect of this diagnosis system was verified through refractory organics and organic overloading shock experiments. Results showed that this diagnosis system could make rapid, accurate and comprehensive diagnosis, predictions and early-warning. MACD algorithm could enhance pattern recognition capacity of status parameters, overcome the lagging of anaerobic process and filter irregular noisy fluctuations of status parameters. MACD index of H2 partial pressure is suitable as sensitive early-warning indicator in the initial shock stage.

12.
Small ; : e2005092, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448126

RESUMO

Pd- and Pd-based catalysts have emerged as potential alternatives to Pt- and Pt-based catalysts for numerous electrocatalytic reactions, particularly fuel cell-related reactions, including the anodic fuel oxidation reaction (FOR) and cathodic oxygen reduction reaction (ORR). The creation of Pd- and Pd-based architectures with large surface areas, numerous low-coordinated atoms, and high density of defects and edges is the most promising strategy for improving the electrocatalytic performance of fuel cells. Recently, 2D Pd-based nanomaterials with single or few atom thickness have attracted increasing interest as potential candidates for both the ORR and FOR, owing to their remarkable advantages, including high intrinsic activity, high electron mobility, and straightforward surface functionalization. In this review, the recent advances in 2D Pd-based nanomaterials for the FOR and ORR are summarized. A fundamental understanding of the FOR and ORR is elaborated. Subsequently, the advantages and latest advances in 2D Pd-based nanomaterials for the FOR and ORR are scientifically and systematically summarized. A systematic discussion of the synthesis methods is also included which should guide researchers toward more efficient 2D Pd-based electrocatalysts. Lastly, the future outlook and trends in the development of 2D Pd-based nanomaterials toward fuel cell development are also presented.

13.
PLoS One ; 16(1): e0244747, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33406129

RESUMO

To date, the effect of both fixed and time-varying individual, social, psychological, environmental, and behavioral characteristics on temporal growth trends in physical activity (PA) among younger individuals remains an under-studied topic. In this paper, we address this gap in previous work by examining how temporal growth trends in PA respond to changing social, environmental, and behavioral characteristics using a large sample of college students (N = 692) who participated in the NetHealth project at the University of Notre Dame and from which fine-grained longitudinal data on physical activity and social interaction were collected unobtrusively via the use of wearables for 637 days (August 16, 2015 to May 13, 2017). These data are augmented by periodic survey data on fixed sociodemographic and psychological variables. We estimate latent growth-curve models for daily activity status, steps, active minutes, and activity calories. We find evidence of both a generalized friendship paradox and a peer effect for PA, with the average PA level of study participants' contacts being on average larger than their own, and with this average level exerting a statistically significant effect on individual PA levels. Notably, there was limited evidence of temporal growth in PA across the 637 days of observation with null temporal effects for three out of the four PA indicators, except for daily steps taken. Finally, we find that social, psychological, and behavioral factors (e.g., large network size, high extroversion levels, and more courses taken) are systematically associated with higher PA levels in this sample. Overall, our findings highlight the importance of social, environmental, and behavioral factors (such as peer networks and daily sociability) in modulating the dynamics of PA levels among college students.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33438257

RESUMO

Although the Turing structures, or stationary reaction-diffusion patterns, have received increasing attention in biology and chemistry, making such unusual patterns on inorganic solids is fundamentally challenging. We report a simple cation exchange approach to produce Turing-type Ag 2 Se on CoSe 2 nanobelts relied on diffusion-driven instability. The resultant Turing-type Ag 2 Se-CoSe 2 material is highly effective to catalyze the oxygen evolution reaction (OER) in alkaline electrolytes with an 84.5% anodic energy efficiency. Electrochemical measurements show that the intrinsic OER activity correlates linearly with the length of Ag 2 Se-CoSe 2 interfaces, determining that such Turing-type interfaces are more active sites for OER. Combing X-ray absorption and computational simulations, we ascribe the excellent OER performance to the optimized adsorption energies for critical oxygen-containing intermediates at the unconventional interfaces.

15.
Int J Med Sci ; 18(3): 646-651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33437199

RESUMO

Objectives: A significant proportion of discharged COVID-19 patients still have some symptoms. Traditional Chinese medicine (TCM) has played an important role in the treatment of COVID-19, but whether it is helpful for discharged patients is still unknown. The aim of this study was to retrospectively analyze the impacts of TCM treatment on the convalescents of COVID-19. Methods: A total of 372 COVID-19 convalescents from February 21 to May 3 in Shenzhen, China were retrospectively analyzed, 291 of them accepted clinically examined at least once and 191 convalescents accepted TCM. Results: After retrospective analysis of the clinical data of convalescents accepted TCM treatment or not, we found that the white blood cell count, as well as serum interleukin-6 and procalcitonin decreased in TCM group. Serum γ-glutamyl transpeptidase was significantly decreased, while prealbumin and albumin increased in TCM group. Red blood cell, hemoglobin, and platelet count increased in TCM group. The mechanisms of TCM treatment might be the overall regulations, including balanced immune response, improved hematopoiesis and coagulation systems, enhanced functions of liver and heart, increased nutrient intake and lipid metabolism. Conclusions: This study suggested that TCM treatment would be beneficial for discharged COVID-19 patients. However, long-term medical observation and further study with randomized trial should be done to confirm this result. Besides, the potential molecular mechanisms of TCM treatment should be further revealed.

16.
Carbohydr Polym ; 253: 117276, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278947

RESUMO

The cbm6e gene from Saccharophagus degradans 2-40 T was cloned and expressed in Escherichia coli. CBM6E contains a glycoside hydrolase family 128 (GH128) catalytic module and a C-terminal carbohydrate-binding module (CBM) grouped into CBM family 6. The purified recombinant CBM6E displayed high substrate specificity toward curdlan as an endo-ß-1,3-glucanase and had maximal activity at pH 6.0 and 35 ℃. The hydrolytic products against curdlan were predominantly laminaritriose (L3) and laminaritetraose (L4) along with a lower amount of laminaripentaose (L5) and laminarihexaose (L6). The CBM6 module selectively enhanced the enzyme activity against curdlan and displayed strict binding specificity to curdlan, no matter in its powder or high-set gel forms. This study laid a foundation for enzymatic degradation of curdlan to produce high-value ß-1,3-glucooligosaccharides at moderate temperatures and provided a novel CBM tag for enzyme immobilization on curdlan.

17.
Cancer Lett ; 498: 142-151, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33232786

RESUMO

Recent advances in immune checkpoint inhibition, which augment T-cell immune responses, have highlighted the potential of exploiting one's immune system to combat cancer. However, only a relatively small number of non-small cell lung cancer (NSCLC) patients benefit from immune checkpoint blockade due to the immunosuppressive tumor microenvironment. Therefore, combination immunotherapies are now being developed to achieve maximal therapeutic benefits. In this study, we assessed whether a novel erlotinib derivative, TD-92, which possesses anti-tumor effects across several cancer cell lines, could enhance anti-PD-1 treatment. Our results demonstrated that the combined treatment of anti-PD-1 and TD-92 resulted in a potent anti-tumor response in a Lewis lung carcinoma cancer model, as evidenced by the reduced tumor growth and increased survival. Analysis of immune cell population counts revealed that TD-92 reduced the number of pro-tumorigenic CD11b+ F4/80+ tumor-associated macrophages, without significantly affecting the total numbers of other major immunocytes. Further experiments showed that TD-92 induced a marked decline in colony stimulating factor 1 receptor (CSF-1R) expression in macrophage cell lines. The results also suggested that c-Cbl-mediated proteasome degradation was involved in TD-92-mediated CSF-1R downregulation. Our data paves the way for the development of additional combination immunotherapies for NSCLC patients.

18.
Eur J Med Chem ; 210: 112965, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33148493

RESUMO

Oxidative stress and inflammation are significant risk factors for neurodegenerative disease. The Keap1-Nrf2-ARE pathway is one of the most promising defensive systems against oxidative stress. Here, dozens of piperlongumine analogues were designed, synthesized, and tested on PC12 cells to examine neuroprotective effects against H2O2 and 6-OHDA induced damage. Among them, 6d was found to be able to alleviate the accumulation of ROS, inhibit the production of NO and downregulate the level of IL-6, which indicated its potential antioxidant and anti-inflammatory activity. Further studies proved that 6d could activate Nrf2 signaling pathway, induce the translocation of Nrf2 from cell cytosol to nucleus and upregulate the related phase II antioxidant enzymes including NQO1, HO-1, GCLC, GCLM and TrxR1. These results confirmed that 6d exerted antioxidant and anti-inflammatory activities by activating Nrf2 signaling pathway. Moreover, the parallel artificial membrane permeability assay indicated that 6d can cross the blood-brain barrier. In general, 6d is promising for further development as a therapeutic drug against oxidative stress and inflammation related neurodegenerative disorders.

19.
Eur J Med Chem ; 210: 113080, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33310286

RESUMO

NUAK, the member of AMPK (AMP-activated protein kinase) family of protein kinases, is phosphorylated and activated by the LKB1 (liver kinase B1) tumor suppressor protein kinase. Recent work has indicated that NUAK1 is a key component of the antioxidant stress response pathway, and the inhibition of NUAK1 will suppress the growth and survival of colorectal tumors. As a promising target for anticancer drugs, few inhibitors of NUAK were developed. With this goal in mind, based on NUAK inhibitor WZ4003, a series of derivatives has been synthesized and evaluated for anticancer activity. Compound 9q, a derivative of WZ4003 by removing a methoxy group, was found to be the most potential one with stronger inhibitory against NUAK1/2 enzyme activity, tumor cell proliferation and inducing apoptosis of tumor cells. By in vivo efficacy evaluations of colorectal SW480 xenografts, 9q suppresses tumor growth more effectively with an excellent safety profile in vivo and is therefore seen as a suitable candidate for further investigation.

20.
Sci Total Environ ; 756: 143951, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33261865

RESUMO

Cadmium (Cd) and copper (Cu) are widely present in foods. However, their adverse effects on human gastric epithelium are not fully understood. Here, human gastric epithelial cells (SGC-7901) were employed to study the toxicity and associated mechanisms of Cd + Cu co-exposure. Their effects on cell viability, morphology, oxidative damage, cell cycle, apoptosis, and the mRNA levels of antioxidases and cell cycle regulatory genes were investigated. Co-exposure to Cd (5 µM)/Cu (10 µM) induced >40% cell viability loss, whereas little effect on cell viability at <10 µM Cd or 40 µM Cu. Compared to individual exposure, co-exposure induced greater oxidative damage by elevating ROS (3.5 folds), malondialdehyde (2.3 folds) and expression of SOD1 and HO-1 besides inhibiting CAT, GPX1 and Nrf2. A marked S cell-cycle arrest was observed in co-exposure, evidenced by more cells staying in the S phase (36%), up-regulation of cyclins-dependent kinase (CDK4) and CDKs inhibitor (p21) and down-regulation of CDK2, CDK6 and p27. Furthermore, higher apoptosis (22%) with floated and round cells occurred in co-exposure group. Our data implicate the cytotoxicity of Cd + Cu co-exposure was higher than individual exposure, and individual assessment would underestimate their potential health risk. Oxidative stress and cell cycle arrest possibly played a role in Cd + Cu induced toxicity and apoptosis in SGC-7901 cells. Our data suggest the importance to reduce Cd in foods to decrease its adverse impacts on human digestive system.


Assuntos
Cádmio , Estresse Oxidativo , Apoptose , Cádmio/toxicidade , Pontos de Checagem do Ciclo Celular , Células Epiteliais , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA