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1.
Environ Int ; 149: 106408, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33548847

RESUMO

BACKGROUND: Although an alteration in sex hormones has been linked to perfluoroalkyl substances (PFAS) in premenopausal women and girls, whether such associations exist in postmenopausal women remains uncertain. OBJECTS: To examine the associations between serum PFAS concentrations and sex hormone levels in postmenopausal women. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016 waves were used. A total of 706 postmenopausal women with information on serum PFAS [perfluorohexane sulfonic acid (PFHxS), pefluorodecanoic acid (PFDA); perfluorononanoic acid (PFNA); linear perfluorooctanoate (n-PFOA); linear perfluorooctane sulfonate (n-PFOS); monomethyl branched isomers of PFOS (Sm-PFOS)], sex hormones indicators [e.g., total testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG)] as well as selected covariates were included. An indicator of circulating free testosterone (FT), and ratio of TT to E2 (TT/E2) were generated. Multiple linear regression accounting for the primary sampling unit, strata, and environmental sampling weights of PFAS was used for association analyses. Effect modification by obesity and type of menopause was explored via stratified analyses as well as the testing of interaction terms. Principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) were conducted to assess these relationships in a multiple PFAS exposure setting. RESULTS: After adjusting for potential confounders, total perfluorooctanoate (TPFOA: n-PFOA + Sb-PFOA) and total perfluorooctane sulfonate (TPFOS: n-PFOS + Sm-PFOS), and their linear and branched isomers were positively associated with two androgen indicators (i.e., TT and FT). PCA results revealed that the principal component (PC) composed of n-PFOA was positively associated with ln (TT) [ß = 0.09, 95% confidential interval (CI): 0.02, 0.16; per ln-ng/mL increase in exposure], and ln (FT) (ß = 0.12, 95% CI: 0.05, 0.2) in overweight/obese [body mass index (BMI) ≥ 25 kg/m2] women, but not in those with BMI < 25 kg/m2. Additionally, among overweight/obese women, PFHxS was positively associated with androgens and negatively with ln (SHBG) (ß = -0.06, 95% CI: -0.12, -0.01). The PC composed of Sm-PFOS, n-PFOS, and PFHxS was positively associated with ln (TT) levels among overweight/obese women. Results from BKMR also confirmed the findings on n-PFOA and PFHxS. CONCLUSIONS: Our study indicates that n-PFOA and PFHxS were positively associated with levels of several androgen indicators in postmenopausal women, particularly among overweight/obese ones. Given the higher risk of cardiometabolic diseases associated with elevated levels of androgens in postmenopausal women, future studies are needed to explore the potential underlying mechanisms.

2.
Invest New Drugs ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475937

RESUMO

Chemotherapy is usually the subsequent treatment for non-small cell lung cancer patients with acquired radioresistance after long-term fractionated radiotherapy. However, few studies have focused on the selection of chemotherapeutic drugs to treat lung adenocarcinoma patients with radioresistance. Our study compared the sensitivity changes of lung adenocarcinoma cells to conventional chemotherapeutic drugs under radioresistant circumstances by using three lung adenocarcinoma cell models, which were irradiated with fractionated X-rays at a total dose of 60 Gy. The results showed that the toxicities of paclitaxel, docetaxel and SN-38 were increased in radioresistant cells. The IC50 values of docetaxel and SN-38 decreased 0 ~ 3 times and 3 ~ 36 times in radioresistant cells, respectively. Notably, the A549 radioresistant cells were approximately 36 times more sensitive to SN-38 than the parental cells. Further results revealed that the downregulation of the efflux transporter BCRP by long-term fractionated irradiation was an important factor contributing to the increased cytotoxicity of SN-38. In addition, the reported miRNAs and transcriptional factors that regulate BCRP did not participate in the downregulation. In conclusion, these results presented important data on the sensitivity changes of lung adenocarcinoma cells to chemotherapeutic drugs after acquiring radioresistance and suggested that irinotecan (the prodrug of SN-38) might be a promising drug candidate for lung adenocarcinoma patients with acquired radioresistance.

3.
J Am Chem Soc ; 143(4): 1846-1853, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33397097

RESUMO

Hypoxia is a common phenomenon among most solid tumors that significantly influences tumor response toward chemo- and radiotherapy. Understanding the distribution and extent of tumor hypoxia in patients will be very important to provide personalized therapies in the clinic. Without sufficient vessels, however, traditional contrast agents for clinical imaging techniques will have difficulty in accumulating in the hypoxic region of solid tumors, thus challenging the detection of hypoxia in vivo. To overcome this problem, herein we develop a novel hypoxia imaging probe, consisting of a hypoxia-triggered self-assembling ultrasmall iron oxide (UIO) nanoparticle and assembly-responding fluorescence dyes (NBD), to provide dual-mode imaging in vivo. In this strategy, we have employed nitroimidazole derivatives as the hypoxia-sensitive moiety to construct intermolecular cross-linking of UIO nanoparticles under hypoxia, which irreversibly form larger nanoparticle assemblies. The hypoxia-triggered performance of UIO self-assembly not only amplifies its T2-weighted MRI signal but also promotes the fluorescence intensity of NBD through its emerging hydrophobic environment incorporated into self-assemblies. In vivo results further confirm that our hypoxic imaging probe can display a prompt MRI signal for the tumor interior region, and its signal enhancement performs a long-term effective feature and gradually reaches 3.69 times amplification. Simultaneously, this probe also exhibits obvious green fluorescence in the hypoxic region of tumor sections. Accordingly, we also have developed a MRI difference value method to visualize the 3D distribution and describe the extent of the hypoxic tumor region within the whole bodies of mice. Due to its notable efficiency of penetration and accumulation inside a hypoxic tumor, our hypoxia imaging probe could also be considered as a potential candidate as a versatile platform for hypoxia-targeted drug delivery, and meanwhile its hypoxia-related therapeutic efficacy can be monitored.

4.
Rapid Commun Mass Spectrom ; 35(1): e8955, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32990383

RESUMO

RATIONALE: Brain metastases are a common complication in patients with non-small-cell lung cancer (NSCLC). Anlotinib hydrochloride is a novel multi-target tyrosine kinase inhibitor (TKI) exhibiting a superior overall response rate for brain metastases from NSCLC. The penetrability of anlotinib and three generations of epidermal growth factor receptor (EGFR) TKIs (osimertinib, afatinib and gefitinib) into brain microvascular endothelial cells (HBMECs) was compared. METHODS: A sensitive quantification method for the four TKIs was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). Anlotinib and the three EGFR TKIs were separated on an ACQUITY BEH C18 column after a direct protein precipitation, and then analyzed using electrospray ionization in positive ion mode. The linearity, accuracy, precision, limit of quantification, specificity and stability were assessed. RESULTS: The four analytes could be efficiently quantified in a single run of 3.8 min. The validation parameters of all analytes satisfy the acceptance criteria of bioanalytical method guidelines. The calibration range was 0.2-200 ng mL-1 for anlotinib and gefitinib, 1-500 ng mL-1 for osimertinib and 1-200 ng mL-1 for afatinib. The penetration of anlotinib across HBMECs was comparable with that of afatinib and gefitinib but less than that of osimertinib. CONCLUSIONS: A sensitive LC/MS/MS method to simultaneously measure anlotinib, osimertinib, afatinib and gefitinib in cell extracts was successfully validated and applied to determine their uptake inside HBMECs, which could pave the way for future research on the role of anlotinib in NSCLC brain metastases.

5.
Environ Pollut ; 267: 115607, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33254666

RESUMO

BACKGROUND: Emerging experimental evidence indicates that organophosphate esters (OPEs) can trigger glucose metabolic disorders. However, human evidence, especially in adolescents, is unavailable. OBJECTIVES: We utilized data from the National Health and Nutrition Examination Survey 2011-2014 to evaluate whether urinary OPEs metabolites were associated with prediabetes and glucose homeostasis. METHODS: A total of 349 adolescents (12-19-year old) who provided at least 8 h fasting blood samples, had urinary OPEs metabolites detected were included. Prediabetes was defined according to the levels of fasting plasma glucose (FPG), 2-h post oral plasma glucose (2 h-OGTT) and glycated hemoglobin A1c (HbA1c). The homeostatic model assessment (HOMA-IR) and the Single Point Insulin Sensitivity Estimator (SPISE) were used to assess insulin resistance and sensitivity, respectively. Multiple binary logistic and linear regressions were used to evaluate the associations with prediabetes and indices of glucose homeostasis. The least absolute shrinkage and selection operator (LASSO) regression was used to assess the associations in a multi-pollutant context. RESULTS: After adjusting for covariates, certain urinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in all adolescents. Stratified analyses by sex revealed that such associations were largely sex-dependent. In females, the multiple pollutant models showed that bis(1,3-32 dichloro-2-propyl) phosphate (BDCIPP) was positively associated with prediabetes [odds ratio (OR) = 2.51, 95%CI:1.29, 4.89, for one scaled unit increase in exposure] and 2 h-OGTT (ß = 0.07, 95%CI:0.01,0.12); bis(2-chloroethyl) phosphate (BCEP) was negatively associated with fasting insulin (ß = -0.10, 95%CI: 0.19,-0.01) and HOMA-IR (ß = -0.10, 95%CI: 0.19,-0.003); and detectable bis(1-choloro-2-propyl) phosphate (BCIPP) (>LOD vs < LOD) was inversely associated with 2 h-OGTT (ß = -0.11, 95%CI: 0.21,-0.02). In males, consistent inverse associations were found for detectable di-n-butyl phosphate (DNBP) with prediabetes, FPG, 2 h-OGTT, fasting insulin and HOMA-IR. CONCLUSION: Urinary OPEs metabolites were associated with prediabetes and indices of glucose homeostasis in adolescents. But such associations varied by sex. Future studies with multiple measurements of OPEs exposure are needed to confirm our findings.

6.
Mol Med ; 26(1): 118, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267791

RESUMO

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Considerable efforts are needed to elucidate the underlying mechanisms for the prevention and treatment of CVDs. Regulator of calcineurin 1 (RCAN1) is involved in both development/maintenance of the cardiovascular system and the pathogenesis of CVDs. RCAN1 reduction protects against atherosclerosis by reducing the uptake of oxidized low-density lipoproteins, whereas RCAN1 has a protective effect on myocardial ischemia/reperfusion injury, myocardial hypertrophy and intramural hematoma/aortic rupture mainly mediated by maintaining mitochondrial function and inhibiting calcineurin and Rho kinase activity, respectively. In this review, the regulation and the function of RCAN1 are summarized. Moreover, the dysregulation of RCAN1 in CVDs is reviewed. In addition, the beneficial role of RCAN1 reduction in atherosclerosis and the protective role of RCAN1 in myocardial ischemia/reperfusion injury, myocardial hypertrophy and intramural hematoma /aortic rupture are discussed, as well as underlying mechanisms. Furthermore, the therapeutic potential and challenges of targeting RCAN1 for CVDs treatment are also discussed.

7.
Infect Dis Ther ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33270206

RESUMO

INTRODUCTION: This study aimed to prospectively investigate the burden of pertussis in southeast Chinese children hospitalized with lower respiratory tract infection (LRTI) during a pertussis outbreak and to compare the outcomes of Bordetella pertussis infection with or without virus coinfections. METHODS: Children < 24 months of age hospitalized with LRTI were prospectively enrolled from January 2017 to December 2019. Demographic and clinical information were recorded, and respiratory tract samples were tested for the presence of B. pertussis and ten common viruses by polymerase chain reaction (PCR). RESULTS: Bordetella pertussis PCR was positive in 6.1% (202/4287) of the patients. Only 146 (72.3%) B. pertussis infections met the Centers for Disease Control and Prevention case definition for pertussis. Among the 202 subjects with B. pertussis infections, 81 (40.1%) were coinfected with at least 1 respiratory virus, with human rhinovirus being the most commonly detected virus (25.7%). No differences in clinical severity were observed between children with single B. pertussis infection and those with virus coinfection [odds ratio (OR) 0.75; 95% confidence interval (CI) 0.39-1.44]. However, children with virus coinfection were significantly more likely to present with radiologically confirmed pneumonia than those with a single B. pertussis infection (OR 2.62; CI 1.39-4.91). CONCLUSIONS: Bordetella pertussis infection contributed to a high proportion of LRTI hospitalizations among southeast Chinese children. There were no significant differences in clinical severity between children with virus coinfection and single B. pertussis infection, although children coinfected with virus coinfection presented with pneumonia more frequently than those with single B. pertussis infection.

8.
Plant J ; 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33345374

RESUMO

Bacterial spot, which is caused by several Xanthomonas species, is an economically important disease in tomato (Solanum lycopersicum). Great efforts have been made for the identification of resistant sources and the genetic analysis of resistance. However, the development of resistant commercial varieties is slow due to the existence of multiple species of the pathogen and a poor understanding of the resistance mechanism in tomato. The current study revealed that the Rx4 gene encodes a nucleotide-binding leucine-rich repeat protein in the wild tomato species Solanum pimpinellifolium and specifically recognizes and confers a hypersensitive response (HR) to Xanthomonas euvesicatoria pv. perforans race T3 expressing the AvrXv3 avirulence protein. Complementation of the Rx4 gene in the susceptible tomato line Ohio 88119 using a transgenic approach resulted in HR, whereas knockout of the gene through CRISPR/Cas9 editing in resistant lines Hawaii 7981 and PI 128216 led to non-HR to race T3. Transcription of Rx4 was not induced by the presence of race T3. Furthermore, the Rx4 protein did not show physical interaction with AvrXv3 but interacted with SGT1-1 and RAR1. Virus-induced gene silencing of SGT1-1 and RAR1 in the resistant line PI128216 suppressed the HR to race T3. Taken together, our study confirms Rx4 is the gene conferring the HR to bacterial spot race T3 and reveals the potential roles of SGT1-1 and RAR1 as signals in the Rx4-mediated HR. This discovery represents a step forward in our understanding of the mechanism of resistance to bacterial spot in tomato and may have important implications for understanding plant-bacterial interactions.

9.
ACS Appl Mater Interfaces ; 12(50): 55659-55674, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33327053

RESUMO

Diabetic skin ulcer is one of the severe complications of diabetes mellitus, which has a high incidence and may cause death or disability. Platelet-rich plasma (PRP) is widely used in the treatment of diabetic wounds due to the effect of growth factors (GFs) derived from it. However, the relatively short half-life of GFs limits their applications in clinics. In addition, the presence of a large amount of proteases in the diabetic wound microenvironment results in the degradation of GFs, which further impedes angiogenesis and diabetic wound healing. In our study, we fabricated a self-healing and injectable hydrogel with a composite of chitosan, silk fibroin, and PRP (CBPGCTS-SF@PRP) for promoting diabetic wound healing. CBPGCTS-SF@PRP could protect PRP from enzymatic hydrolysis, release PRP sustainably, and enhance the chemotaxis of mesenchymal stem cells. The results showed that it could promote the proliferation of repair cells in vitro. Moreover, it could enhance wound healing by expediting collagen deposition, angiogenesis, and nerve repair in a type 2 diabetic rat model and a rat skin defect model. We hope that this study will offer a new treatment for diabetic nonhealing wounds in clinics.

10.
Biomed Res Int ; 2020: 2147367, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33344631

RESUMO

Ammonium (NH4 +) plays key roles in plant growth, development, fruit quality, and yield. In plants, NH4 + uptake and transport are facilitated by NH4 + transporters (AMT). However, molecular mechanisms and physiological functions of type-II AMT (AMT2) transporters in fruit trees are still unclear, especially in peach. In this study, we cloned and characterized an AMT2 family gene from peach, PpeAMT3;4, and determined its function in yeast mutant. Expression analysis showed that PpeAMT3;4 was majorly expressed in peach roots and significantly decreased by NH4 + excess but had no response to NH4 + deficiency. Functional determination and 15nitrogen-labeled NH4 + uptake assay in yeast cells implied that PpeAMT3;4 was a typical high-affinity transporter, with a K m value of 86.3 µM, that can uptake external NH4 + in yeast cells. This study provides gene resources to uncover the biological function of AMT2 transporters and reveals molecular basis for NH4 + uptake and nitrogen (N) nutrition mechanisms in fruit trees.

11.
Biomed Pharmacother ; 133: 110991, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33227713

RESUMO

As one of major chronic complications of diabetes, diabetic foot ulcer (DFU) is the main cause of disability and death. The clinical diagnosis and prognosis of DFU is inadequate. For clinicians, if the risk stratification of DFU can be obtained earlier in diabetic patients, the hospitalization, disability and mortality rate will be reduced. In addition to the inflammatory biomarkers that have been widely concerned and used, e.g., procalcitonin, pentraxin-3, C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor-α (TNF-α), etc., a more comprehensive prediction of the risk and severity of DFU is needed to reflect new biomarkers for therapeutic intervention effects. Along with the development of systems biology technology, genomics, proteomics, metabolomics and microbiome have been used in the studies on DFU for better understanding of the disease. In this review, new biomarkers that are expected to assist in the accurate diagnosis and risk stratification of DFU will be discussed and summarized in detail.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33188921

RESUMO

STUDY OBJECTIVE: To investigate pregnancy and obstetric outcomes of patients with intrauterine adhesions (IUAs) after treatment with in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) and fresh embryo transplantation after transcervical resection of adhesions (TCRA). DESIGN: Retrospective cohort study. SETTING: University-based reproductive medical center. PATIENTS: A total of 535 patients with IUAs and with a history of TCRA and 1605 matched patients without a history of IUAs underwent IVF-ICSI and received fresh embryo transfers. INTERVENTIONS: Between January 2014 and December 2018, all patients underwent IVF-ICSI treatment and received fresh embryo transfers. MEASUREMENTS AND MAIN RESULTS: The patients in the TCRA group were matched with the control group according to strict criteria. Pregnancy and obstetric outcomes were compared. There were no significant differences in clinical pregnancies, ectopic pregnancies, live births, preterm births, and obstetric outcomes between the 2 groups (p >.05). However, the TCRA group had a higher risk of miscarriage than the control group (p = .048). CONCLUSION: TCRA improved the reproductive outcomes of patients with IUAs, but the risk of miscarriage was higher than that in the general population. To avoid miscarriage, careful monitoring is critical for pregnant patients with a history of TCRA who undergo embryo transfers during IVF treatment.

13.
Biomed Chromatogr ; : e5026, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169423

RESUMO

Bidens bipinnata L. is a folk medicinal plant in China that shows significant antihyperlipidemia effectiveness. However, studies of the underlying mechanism study are lacking. In order to explore the potential action sites and the underlying mechanism of treating hyperlipidemic, this work undertook tissue distribution and molecular docking research on the markers of B. bipinnata L., which were obtained through serum pharmacochemistry and network database retrieval. The results showed that seven compounds (gallic acid, protocatechuic acid, rutin, hyperoside, bipinnate polyacetylenicloside, luteolin and quercetin) were screened out as markers. Owing to the diversity of chemical structures, they exhibited an inconsistent trend in tissue distribution. However, all of them had high levels in the liver and no specific distribution in other tissues. More interestingly, seven proteins-HMGCR (1HWK), NR3C1 (4P6W), CYP1A2 (2HI4), RXRA (4PP3), CES1 (1MX1), HSD11B1 (2RBE) and CYP1A1 (4I8V)-showed significant binding affinity with three or more markers, suggesting that they may be the target proteins of B. bipinnata L. This study preliminarily sheds light on the tissue distribution and targets of B. bipinnata L., providing some useful information on the underlying mechanisms of the antihyperlipidemia effect.

14.
Mol Med Rep ; 22(6): 4967-4980, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174001

RESUMO

Muscle atrophy is a severe clinical problem involving the loss of muscle mass and strength that frequently accompanies the development of numerous types of cancer, including pancreatic, lung and gastric cancers. Cancer cachexia is a multifactorial syndrome characterized by a continuous decline in skeletal muscle mass that cannot be reversed by conventional nutritional therapy. The pathophysiological characteristic of cancer cachexia is a negative protein and energy balance caused by a combination of factors, including reduced food intake and metabolic abnormalities. Numerous necessary cellular processes are disrupted by the presence of abnormal metabolites, which mediate several intracellular signaling pathways and result in the net loss of cytoplasm and organelles in atrophic skeletal muscle during various states of cancer cachexia. Currently, the clinical morbidity and mortality rates of patients with cancer cachexia are high. Once a patient enters the cachexia phase, the consequences are difficult to reverse and the treatment methods for cancer cachexia are very limited. The present review aimed to summarize the recent discoveries regarding the pathogenesis of cancer cachexia­induced muscle atrophy and provided novel ideas for the comprehensive treatment to improve the prognosis of affected patients.

15.
Sci Adv ; 6(41)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33036962

RESUMO

How much the observed long-term variability of tropical cyclone (TC) activity is due to anthropogenic global warming (GW) or internal climate variability remains unclear, limiting the confidence in projected future change in TC activity. Here, the relative contributions of GW and the Interdecadal Pacific Oscillation (IPO) to the long-term variability of TC track density (TCTD) over the North Pacific (NP) are quantified on the basis of statistical analyses and climate model simulations. Results show that historical GW mainly reduced (increased) TCTD over the western (eastern) NP, while the positive (negative) IPO corresponds to a NP basin-wide increase (decrease) in TCTD except in some coastal regions. The IPO has a much greater impact on TCTD over the western NP than GW, while the IPO and GW impacts are about equal over the eastern NP during 1960-2019. These findings have important implications for projecting future TC activity over the NP.

16.
Front Pharmacol ; 11: 579068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041823

RESUMO

Integrins are the adhesion molecules and receptors of extracellular matrix (ECM). They mediate the interactions between cells-cells and cells-ECM. The crosstalk between cancer cells and their microenvironment triggers a variety of critical signaling cues and promotes the malignant phenotype of cancer. As a type of transmembrane protein, integrin-mediated cell adhesion is essential in regulating various biological functions of cancer cells. Recent evidence has shown that integrins present on tumor cells or tumor-associated stromal cells are involved in ECM remodeling, and as mechanotransducers sensing changes in the biophysical properties of the ECM, which contribute to cancer metastasis, stemness and drug resistance. In this review, we outline the mechanism of integrin-mediated effects on biological changes of cancers and highlight the current status of clinical treatments by targeting integrins.

17.
Front Plant Sci ; 11: 1183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983188

RESUMO

Silicon (Si) has been known to enhance salt resistance in plants. In this experiment, 4-weeks-old alfalfa seedlings were exposed to different NaCl concentrations (0-200 mM) with or without 2 mM Si for two weeks. The results showed that NaCl-stressed alfalfa seedlings showed a decrease in growth performance, such as stem extension rate, predawn leaf water potential (LWP) and the chlorophyll content, potassium (K+) concentration, as well as the ratio of potassium/sodium ion (K+/Na+). In contrast, NaCl-stressed alfalfa seedlings increased leaf Na+ concentration and the malondialdehyde (MDA) level, as well as the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in alfalfa leaves. Besides, exogenous Si application enhanced photosynthetic parameters of NaCl-stressed alfalfa seedlings, which was accompanied by the improvement in predawn LWP, level of chlorophyll content, and water use efficiency (WUE). The Si-treated plants enhanced salinity tolerance by limiting Na+ accumulation while maintaining K+ concentration in leaves. It also established K+/Na+ homeostasis by increasing K+/Na+ radio to protect the leaves from Na+ toxicity and thereby maintained higher chlorophyll retention. Simultaneously, Si-treated plants showed higher antioxidant activities and decreased MDA content under NaCl stress. Our study concluded that Si application enhanced salt tolerance of alfalfa through improving the leaves photosynthesis, enhancing antioxidant performance and maintaining K+/Na+ homeostasis in leaves. Our data further indicated exogenous Si application could be effectively manipulated for improving salt resistance of alfalfa grown in saline soil.

18.
Front Oncol ; 10: 1617, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984029

RESUMO

Objective: Bortezomib is one of the important drugs that have made breakthrough progress in multiple myeloma (MM) in the past 10 years. However, the heterogeneity of its efficacy makes it difficult to predict the risk of disease progression. The purpose of this study is to determine the prognostic significance of the (neutrophils + monocytes)/lymphocytes ratio (NMLR) in newly diagnosed MM patients who received BCD regimen therapy in terms of progression-free survival (PFS). Methods: A total of 150 patients who fulfilled the International Myeloma Working Group (IMWG) criteria were enrolled in the study retrospectively. The prognostic value of NMLR was evaluated by 150 patients with MM who were treated with BCD (bortezomib + cyclophosphamide + dexamethasone) regimen therapy. NMLR was calculated by the ratio of (neutrophils + monocyte) to lymphocytes. According to receiver operating characteristic curves, the cutoff value was 1.90. The patients were divided into high NMLR group (H-NMLR, NMLR ≥1.90) and low NMLR group (L-NMLR, NMLR <1.90). The clinical characteristics, treatment responses and PFS of the two groups were analyzed. Results: The median age of the patients was 61 years. Fifty-five (36.67%) patients showed lower NMLR at initial diagnosis. Although NMLR was unable to discriminate prognosis in ISS stage I/II patients, interestingly, the addition of NMLR to the ISS further defined prognosis particularly in stage III. Low-NMLR group who achieved early immune reconstruction significantly higher than that of the high-NMLR group (P < 0.001). NMLR value was 1.98 ± 1.02 for the patients who achieved early immune reconstruction, which was 3.26 ± 2.52 for the patients without immune reconstruction (P < 0.05). Compared with the H-NMLR group, the levels of ß2-microglobulin, serum creatinine and calcium were lower, and the very good partial response or better (≥VGPR) ratio was higher in L-NMLR group. The L-NMLR group experienced a superior median PFS compared with the H-NMLR group (24.0 versus 15.5 months; P < 0.001). In addition, several other prognostic factors of PFS were estimated, including the high-risk cytogenetics, ß2-microglobulin and the depth of treatment response 3 months after treatment with BCD regimen. Moreover, NMLR was an independent predictor of PFS including non-high risk cytogenetics (0.587; P = 0.031). Conclusion: In patients with newly diagnosed MM undergoing BCD regimen, the NMLR <1.90 was an independent prognostic factor for PFS as well as early immune reconstruction and lower disease burden.

19.
Langmuir ; 36(41): 12299-12308, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32988201

RESUMO

Recently, porous organic cages (POCs) have emerged as a novel porous material with many merits and are widely utilized in many application fields. In this work, for the first time, molecular dynamics simulations were performed to investigate the mechanism of lysozyme adsorption onto the CC3 crystal, a kind of widely studied POC material. The simulation results show that lysozyme adsorbs onto the surface of CC3 with "top end-on," "back-on," or "side-on" orientations. It is found that the van der Waals interaction is the primary contribution to the binding; the conformation of the lysozyme is well preserved during the adsorption process. This provides some evidence for its biocompatibility and feasibility in biorelated applications. Arginine plays an important role in mediating the adsorption through nonpolar aliphatic chains. More importantly, the distribution and structure of the water layer on the POC surface has a significant impact on adsorption. This study provides insights into the development of POC materials with defined morphologies for the adsorption of biomolecules and may help the rational design of biorelated systems.

20.
Transl Pediatr ; 9(4): 541-550, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953552

RESUMO

Background: Viral etiology and atopic characteristics, e.g., allergens and fractional exhaled nitric oxide (FeNO), play essential roles in asthma development. This study aimed to investigate associations among them in children at high risk of developing asthma to guide reliable diagnosis and treatment of wheezing. Methods: From April 2016 to August 2017, 135 children aged <3 years identified as being at high risk of asthma and hospitalized for lower respiratory tract infection (LRTI) with wheezing were recruited as research subjects (observation group). Real-time fluorescent polymerase chain reaction (PCR) was used to explore their etiology. Samples were also evaluated with Phadiatop (Pharmacia Diagnostics AB, Uppsala, Sweden). Additionally, 200 non-asthmatic, non-allergic, healthy children who were screened and followed up in the Echocardiography clinic during the study period were recruited as a healthy control group for FeNO measurement, and the observation group also underwent FeNO measurement. Results: Among the observation group, viruses were positively detected in 49.63%. The most often detected virus was human rhinovirus (HRV; 25.19%). Compared with children aged <12 months, those aged 1-3 years were more susceptible to HRV infection and had lower sensitivity rates for inhalant allergens and higher T-IgE. The virus-detected group had a higher sensitivity rate for inhalant allergens compared with the virus-undetected group. FeNO in the observation group was lower than that in the healthy control group. The second-wheezing group had higher sensitivity rates for dust mites and fungi and higher T-IgE levels compared with the first-wheezing group. Conclusions: HRV was the most common viral pathogen present during an asthmatic attack in infants and young children at elevated risk of asthma. Allergy is a risk factor for both initial wheezing and repeated wheezing. Inhalant allergen-sensitive children are more susceptible than others to viral infection.

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