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1.
Toxicol In Vitro ; 62: 104668, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629073

RESUMO

Methamphetamine (MA) has a high uptake in lung, but the precise mechanism of MA-induced lung toxicity remains unclear. The aim of this study is to investigate the role of MA abuse in remodeling of pulmonary arteries and to explore the possible correlation of the association of the remodeling with the redox imbalance in pulmonary arterial smooth muscle cells (PASMCs). Wistar rats were randomly divided into control group and MA group for the experimental study. We employed H&E staining, western blot, immunofluorescence, knockdown, flow in our experimental approach. Our studies shows that chronic exposure to MA led to weight loss, increased pulmonary arterial pressure, hypertrophy of right ventricle and remodeling of pulmonary arterial wall of rats. Our cell culture study with PASMCs indicates that MA significantly induced the imbalance between proliferation and apoptosis by upregulating the level of PCNA, Bcl-2 and reduction in the expression of BAX and Caspase 3. MA markedly prevented the nuclear translocation of Nrf2 to inhibit antioxidation. The knockdown of Nrf2 expression using siRNA significantly elevated the expression of SOD2/GCS and the production of ROS in PASMCs and even scaled up the amount of PASMCs induced by MA. Linear regression analysis showed that knockdown of Nrf2 promoted the positive correlation of relative ROS level with proliferation of PASMCs. Therefore, chronic exposure to MA induces pulmonary arterial remodeling by Nrf2-mediated imbalance of redox system to aggravate oxidative stress, and Nrf2 is a possible target for the treatment of MA-lung toxicity.

2.
Health Policy Plan ; 34(Supplement_2): ii56-ii66, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31723970

RESUMO

Integration of health services has been pursued worldwide. Diversity in integration approaches and in the contexts in which integrated programmes operate, however, hinders comparative analysis of care integration in both high-income countries (HICs) and low- and middle-income countries (LMICs). This study evaluates an HIC programme implemented in a delivery system resembling those of LMICs, especially its weak primary care system. The programme, Taiwan's Family Doctor Plan (FDP), targets high-cost and chronic patients, incorporating key elements of integrated care, viz., case management, multidisciplinary teams and care pathways. This study estimates the effects of shifting from usual to integrated care and locates contextual factors that may distort programme implementation. To estimate programme effects, difference-in-differences analysis is applied to a balanced panel comprising >160 000 patients over 2009-13. Because physician participation is voluntary, a propensity score matching method is used to match providers. The research findings reveal that introduction of the FDP has not reoriented the model of care from fragmented towards integrated health services. It reduces continuity of care and has no effect on co-ordination of care. Regarding quality of care, the FDP is shown to have no effect on avoidable admissions and increases drug injections and emergency department visits. Several contextual factors may serve as barriers that impede elements of FDP from generating desirable outcomes. These include absence of registration and gatekeeping systems; limited capacities of clinics; and preponderance of fee-for-service remuneration. These findings suggest that HIC design elements may not be directly transferrable to settings with weak primary care systems, as is typical of LMIC healthcare. Changes at the system level, such as establishing regular sources of care, may be necessary before elements of integrated care are introduced to a weaker primary care system.

3.
J Mol Diagn ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751678

RESUMO

Myeloid neoplasms are a heterogenous group of neoplasms including acute myeloid leukemia (AML), myeloproliferative neoplasms, myelodysplastic syndrome, and myeloproliferative neoplasms / myelodysplastic syndrome. Genetic abnormalities are used as diagnostic, prognostic, and predictive biomarkers in patients with these diseases. Here, we describe the clinical validation of the Oncomine Myeloid Research (OMR) next-generation sequencing panel that interrogates for 40 genes and 29 fusion genes commonly seen in myeloid neoplasms. Our validation set of 77 DNA samples included acute and chronic myeloid neoplasms with 91 single nucleotide variants and small indels. The 71 RNA samples from patients with AML included most of the AML-defining translocations. The OMR on the Ion Torrent S5 platform shows good performance in terms of depth of coverage, on-target reads, and uniformity. The panel achieved 91.3% and 100% concordance with reference DNA and RNA samples, with a clinical sensitivity and specificity of 96.7% and 100% for DNA, and 99.8% and 100% for RNA, respectively. Precision and reproducibility were 100% and the lower limit of detection was generally 5% VAF for DNA and 2-log reduction from initial value for RNA fusion genes. In conclusion, the OMR panel is a highly accurate and reproducible next-generation sequencing panel for the detection of common genetic alteration in myeloid neoplasms.

4.
Biomater Sci ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674627

RESUMO

Hydrogen polysulfides (H2Sn, n > 1) belong to sulfane sulfur in the reactive sulfur species (RSS) family and play significant roles in maintaining biological homeostasis in organisms. The detection of H2Sn in living systems is essential, but further understanding of its "intact" function in living cells has been limited, owing to the lack of appropriate analytical tools. In this work, a new fluorescent probe PP-PS was designed for the detection of endogenous H2Sn. The probe has a large Stokes shift (178 nm), low detection limit (1 nM), and short response time (1 minute). Besides, PP-PS was successfully applied in the imaging of endogenous H2Sn in lysosomes of living cancer cells, xenograft mouse tumor tissues, and LPS-induced mouse inflammation tissues. These results revealed that the probe PP-PS could act as a new fluorescence imaging tool to study the function of intracellular hydropolysulfides.

5.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(5): 505-508, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31721498

RESUMO

OBJECTIVE: To study the clinical features and treatments of congenital submandibular duct dilatation. METHODS: Seven children with congenital submandibular duct dilatation from January 2008 to March 2018 were included in this study, whose average age was 5 months and 22 days. The clinical manifestations are unilateral swelling of the mouth floor. All seven children underwent sublingual gland resection, submandibular gland dilatation catheter resection, and catheter reroute under general anesthesia. Intraoperatively, the orifice of the submandibular gland was constricted and part of the catheter was dilated. RESULTS: All seven patients had good healing without swelling or cyst formation. CONCLUSIONS: Congenital submandibular duct dilatation occurs at a young age. Early diagnosis and treatment can help prevent further expansion of the catheter and avoid gland atrophy, feeding difficulty, and breathing obstruction. Simultaneous excision of the sublingual gland can avoid the formation of postoperative sublingual cyst.


Assuntos
Rânula , Ductos Salivares , Criança , Dilatação , Humanos , Lactente , Glândula Sublingual , Glândula Submandibular
6.
J Exp Clin Cancer Res ; 38(1): 438, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666108

RESUMO

BACKGROUND: Glutathione S-transferase zeta 1 (GSTZ1) is the penultimate enzyme in phenylalanine/tyrosine catabolism. GSTZ1 is dysregulated in cancers; however, its role in tumorigenesis and progression of hepatocellular carcinoma (HCC) is largely unknown. We aimed to assess the role of GSTZ1 in HCC and to reveal the underlying mechanisms, which may contribute to finding a potential therapeutic strategy against HCC. METHODS: We first analyzed GSTZ1 expression levels in paired human HCC and adjacent normal tissue specimens and the prognostic effect of GSTZ1 on HCC patients. Thereafter, we evaluated the role of GSTZ1 in aerobic glycolysis in HCC cells on the basis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Furthermore, we assessed the effect of GSTZ1 on HCC proliferation, glutathione (GSH) concentration, levels of reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor 2 (NRF2) signaling via gain- and loss- of GSTZ1 function in vitro. Moreover, we investigated the effect of GSTZ1 on diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) induced hepatocarcinogenesis in a mouse model of HCC. RESULTS: GSTZ1 was downregulated in HCC, thus indicating a poor prognosis. GSTZ1 deficiency significantly promoted hepatoma cell proliferation and aerobic glycolysis in HCC cells. Moreover, loss of GSTZ1 function depleted GSH, increased ROS levels, and enhanced lipid peroxidation, thus activating the NRF2-mediated antioxidant pathway. Furthermore, Gstz1 knockout in mice promoted DEN/CCl4-induced hepatocarcinogenesis via activation of the NRF2 signaling pathway. Furthermore, the antioxidant agent N-acetylcysteine and NRF2 inhibitor brusatol effectively suppressed the growth of Gstz1-knockout HepG2 cells and HCC progression in Gstz1-/- mice. CONCLUSIONS: GSTZ1 serves as a tumor suppressor in HCC. GSH depletion caused by GSTZ1 deficiency elevates oxidative stress, thus constitutively activating the NRF2 antioxidant response pathway and accelerating HCC progression. Targeting the NRF2 signaling pathway may be a promising therapeutic approach for this subset of HCC.

7.
Aging (Albany NY) ; 11(19): 8604-8622, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596731

RESUMO

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses. This study aimed to investigate the function and mechanisms of 5-MTP in interventional procedure-induced restenosis. We found that after mouse femoral artery denudation with a guide wire, 5-MTP accelerated recovery of endothelium in the denuded area and reduced vascular leakage and intimal thickening. 5-MTP increased endothelial cell proliferation in the denuded arteries and rescued TNF-α-reduced endothelial cell proliferation and migration, likely via maintaining vascular endothelial growth factor receptor 2 activation. In contrast, 5-MTP preserved differentiated phenotype of medial vascular smooth muscle cells (VSMCs) and decreased VSMC proliferation and migration. Furthermore, 5-MTP maintained expression levels of critical transcription factors for VSMC marker gene expressions via attenuated activation of p38 MAPK and NFκB-p65. Our findings uncover a novel protective mechanism of 5-MTP in restenosis. In response to denudation injury, 5-MTP attenuates intimal hyperplasia via concerted but opposing actions on endothelial cells and VSMCs. Taken together, our results suggest that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.

8.
Am J Surg Pathol ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31567202

RESUMO

The pineal parenchymal tumors of intermediate differentiation (PPTIDs) are extremely rare tumor entities. They exhibit low-risk (grade II) and high-risk (grade III) malignancies, which may lead to different therapies and prognosis. However, the histological grading criteria remains elusive, and novel biomarkers may be helpful to differentiate the grade of PPTIDs. Immunohistochemical staining for CD24, PRAME, POU4F2, and HOXD13, and their clinicopathologic analyses were performed in pineal parenchymal tumors and other tumors in the pineal region. CD24 and PRAME were expressed in 9/11 (81.8%) and 8/11(72.7%) cases of PPTIDs grade III, compared with 6/18 (33.3%) and 5/18(27.8%) cases of PPTIDs grade II. The levels of CD24 and PRAME were significantly higher in PPTIDs grade III than grade II. However, there were no differences of HOXD13 and POU4F2 expression levels in PPTIDs grade II and grade III. Interestingly, high expression of CD24 and PRAME were prevalently found in high-grade tumors of the central nervous system. In addition, PPTIDs patients with high expression levels of CD24 and PRAME exhibited a significant shorter survival time. The results of PPTIDs grading by CD24 and PRAME were mostly consistent with WHO criteria, except for two cases. According to the prognostic information of patients, we found that the combination of CD24 and PRAME expression for grading PPTIDs might be more valuable than WHO criteria only. CD24 and PRAME are novel markers for grading and prognostic evaluation of PPTIDs that may be helpful to determine the therapeutic decision for PPTIDs patients.

9.
Int J Biol Macromol ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31622714

RESUMO

This study tested the potential of forming soluble complex with pectin (PEC) on enhancing physical stability of water-soluble myofibrillar protein (WSMP) near the isoelectric point (pI, pH 5.00-5.50). After incorporation of PEC at the mixing ratio of 10:1 and 5:1, WSMP suspension maintained transparent state at 0.05 wt% while a homogeneous monophase at 1.00 wt% around pI, indicating the formation of soluble WSMP-PEC complex. When mixing the two biopolymers, charge neutralization was observed, revealing the electrostatic attraction between positively charged patches of WSMP and negatively charged carboxyl sites of PEC. Steady shear results showed a reduced viscosity of WSMP-PEC complex when dropping the pH to 5.00, this may be related to the declined biopolymer net charge and water trapping. Oscillatory data suggest the formation of highly-interconnected network in soluble WSMP-PEC complex, thus decreasing pH or biopolymer ratio can enhance their interactions and thereby lead to stronger and more stable microstructure. Thermal denaturation temperature of WSMP was significantly enhanced through the formation of WSMP-PEC soluble complexes. Overall, complexation with PEC improved the colloidal and thermal stability of WSMP around the pI, which evidenced the potential of applying tailor designed protein-polysaccharide complex in formulating muscle protein-based beverages.

11.
Plast Reconstr Surg ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31577662

RESUMO

BACKGROUND: With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid (HA), the incidence of HA embolism has also commensurately increased. HA embolism leads to serious complications including blindness, eye and eyelid movement disorders, skin necrosis and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for HA embolism by Intra-arterial thrombolysis (IAT) therapy. METHODS: In this study, we included 24 patients with a decrease in visual acuity and other complications induced by facial HA injection. These patients underwent emergency IAT therapy by injection of hyaluronidase (500-1,500 units) alone or hyaluronidase (750-1,500 units) combined with urokinase (100,000-250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy. RESULTS: In the 24 patients, 10 patients (42%) ultimately had improvements to visual acuity, even in cases when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases the patients' facial skin necrosis was restored to nearly normal appearance. In addition, we found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone. CONCLUSION: Our results indicate that IAT therapy is beneficial to patients suffering from blindness induced by HA embolism. IAT therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision , and was also beneficial in the recovery from other serious complications including eye movement disorder, eye edema, headaches, and skin necrosis.

12.
Cancer Res Treat ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31476848

RESUMO

Purpose: This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods: Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed. Results: For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen-specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved. Conclusion: Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

13.
Oncogene ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477839

RESUMO

As an inhibitor of heat shock proteins (HSPs), KNK437 has been reported to play an anti-tumor role in several cancers. But its therapeutic effect and mechanisms in colorectal cancer (CRC) remain unclear. Here, KNK437 sharply inhibited the level of DnaJ heat shock protein family (Hsp40) member A1 (DNAJA1), followed by DNAJB1, but had little effect on the levels of HSP27, HSP105, HSP90, and HSP70 in CRC cells. DNAJA1 promoted CRC cell proliferation in vitro and tumor growth and metastasis in vivo. Mechanistically, DNAJA1 was activated by E2F transcription factor 1 (E2F1) and then promoted cell cycle by stabilizing cell division cycle protein 45 (CDC45), which could be reversed by KNK437. DNAJA1 was significantly upregulated in CRC tissues and positively correlated with serosa invasion, lymph node metastasis. High level of DNAJA1 predicted poor prognosis for CRC patients. Its expression was highly linked with E2F1 and CDC45 in CRC tissues. More importantly, KNK437 significantly suppressed the growth of DNAJA1 expressing tumor in vivo. The combined treatment of KNK437 with 5-FU/L-OHP chemotherapy reduced liver metastasis of CRC. These data reveal a novel mechanism of KNK437 in anti-tumor therapy of CRC and provides a newly therapeutic strategy with potential translation to the CRC patients.

14.
BMC Pediatr ; 19(1): 324, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506066

RESUMO

Following publication of the original article [1], the editor informed that error was found.

15.
Phys Med ; 64: 40-44, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31515034

RESUMO

PURPOSE: We investigate the effect of the GafChromic™ film EBT3 model absorbed dose energy response when used for dose measurements around low-energy photon sources. Monte Carlo based correction procedure in synergy with appropriate calibration curves was shown to provide more accurate absorbed dose (either relative or absolute). An assessment was made of possible dose errors that might be encountered if such energy dependent response is ignored. METHODS: We measured PDDs in water from a Xoft 50 kVp source using EBT3 film, and compared to PDD measurements acquired with a PTW-TN34013 parallel-plate ionization chamber. For the x-ray source, we simulated spectra using the EGSnrc (BEAMnrc) Monte Carlo code, and calculated Half Value Layer (HVL) at different distances from the source in water. Measurement strips of EBT3 film were positioned at distances of 2-6 cm from the Xoft source in a water phantom using a custom-made holder and irradiated simultaneously. RESULTS: Our results show that film calibration curves obtained at beam qualities near the effective energy of the Xoft 50 kVp source in water lead to variation in absorbed dose energy dependence of the response of around 5%. However, if the calibration curve was established in an MV beam quality, the error in absorbed dose could be as large as 20%. CONCLUSION: Accurate dose measurements using radiochromic films at low photon energies require that the radiochromic film dosimetry system be calibrated at appropriate corresponding low energies, as large absorbed dose errors are expected when film calibration is performed in MV beam qualities.

16.
Arch Microbiol ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31535159

RESUMO

A gram-stain-negative, aerobic, non-spore-forming, rod-shaped, non-motile bacterium strain R4HLG17T was isolated from Tamarix ramosissima roots growing in Kumtag desert. The strain grew at salinities of 0-16% (w/v) NaCl (optimum 5-6%), pH 5-9 (optimum 7) and at 16-45 °C. Based on 16S rRNA gene sequence similarity, strain R4HLG17T belonged to the family Halomonadaceae and was most closely related to Halomonas lutea DSM 23508T(95.1%), followed by Halotalea alkalilenta AW-7T(94.8%), Salinicola acroporae S4-41T(94.8%), Salinicola halophilus CG4.1T(94.6%), and Larsenimonas salina M1-18T(94.4%). Multilocus sequence analysis (MLSA) based on the partial sequences of 16S rRNA, atpA, gyrB, rpoD, and secA genes indicated that the strain R4HLG17T formed an independent and monophyletic branch related to other genera of Halomonadaceae, supporting its placement as a new genus in this family. The draft genome of strain R4HLG17T was 3.6 Mb with a total G + C content of 55.1%. The average nucleotide identity to Halomonas lutea DSM 23508T was 83.5%. Q-9 was detected as the major respiratory quinone and summed feature 8 (C18:1ω7c/C18:1ω6c), summed feature 3 (C16:1ω7c/C16:1ω6c), and C16:0 as predominant cellular fatty acids. On the basis of chemotaxonomic, phylogenetic, and phenotypic evidence, strain R4HLG17T is concluded to represent a novel species of a new genus within Halomonadaceae, for which the name Phytohalomonas tamaricis gen. nov., sp. nov., is proposed. The type strain is R4HLG17T (=ACCC 19929T=KCTC 52415T).

17.
BMC Pediatr ; 19(1): 264, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31362719

RESUMO

BACKGROUND: The relationship between birth weight and blood pressure has not been well explored in Chinese children and adolescents. The aim of this study was to investigate the relationship between birth weight and childhood blood pressure in China. METHODS: A total of 15324 children and adolescents (7919 boys and 7405 girls) aged 7-17 years were stratified into six birth weight groups. Analysis of covariance and binary logistic regression were used to analyse the relationship between birth weight and blood pressure while controlling for potential confounding factors, including age, gestational age, season of birth and area of residence. RESULTS: The group with birth weights from 2500 to 2999 g had the lowest prevalence of hypertension (8.9%). Lower birth weight children (< 2000 g) had significantly higher systolic blood pressure (SBP) (106.00 ± 0.72, P = 0.017), and children with heavier birth weights also had higher SBP (3500-3999 g, 105.13 ± 0.17, P < .001; ≥ 4000 g, 105.96 ± 0.27, P < .001). No significant relationship was found between birth weight and diastolic blood pressure (DBP). The overall rate of hypertension was 10.8% (12.1% in boys and 9.4% in girls). The median weight group (2500-2999 g) had the lowest rate of hypertension (8.9%). Compared with children in the median weight group, children with lower birth weight had a higher prevalence of hypertension (< 2000 g, OR = 1.85, 95% CI = 1.25-2.74; 2000-2499 g, OR = 1.57, 95% CI = 1.15-2.13), and groups with higher birth weights also had higher risks of hypertension (3500-3999 g, OR = 1.22, 95% CI = 1.02-1.45; ≥ 4000 g, OR = 1.42, 95% CI = 1.16-1.74). CONCLUSIONS: Excluding the confounding effect of obesity, a U-shaped relationship between birth weight and risk of hypertension was found in children and adolescents in Chinese cities. Birth weight significantly influences SBP but has a minimal effect on DBP. Further basic research on foetal development and programming may shed light on this phenomenon.

18.
Plant Dis ; 103(10): 2541-2547, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432772

RESUMO

To prevent the spread of anthracnose in strawberry plants and characterize the metabolic changes occurring during plant-pathogen interactions, we developed a method for the early diagnosis of disease based on an analysis of the metabolome by gas chromatography-mass spectrometry. An examination of the metabolic profile revealed 189 and 202 total ion chromatogram peaks for the control and inoculated plants, respectively. A partial least squares discriminant analysis (PLS-DA) model was conducted for the reliable and accurate discrimination between healthy and diseased strawberry plants, even in the absence of disease symptoms (e.g., early stages of infection). ANOVA (analysis of variance) and orthogonal partial least squares analysis (OPLS) identified 20 metabolites as tentative biomarkers of Colletotrichum theobromicola infection (e.g., citric acid, d-xylose, erythrose, galactose, gallic acid, malic acid, methyl α-galactopyranoside, phosphate, and shikimic acid). At least some of these potential biomarkers may be applicable for the early diagnosis of anthracnose in strawberry plants. Moreover, these metabolites may be useful for characterizing pathogen infections and plant defense responses. This study confirms the utility of metabolomics research for developing diagnostic tools and clarifying the mechanism underlying plant-pathogen interactions. Furthermore, the data presented herein may be relevant for developing new methods for preventing anthracnose in strawberry seedlings cultivated under field conditions.


Assuntos
Biomarcadores , Colletotrichum , Fragaria , Cromatografia Gasosa-Espectrometria de Massas , Metabolômica , Biomarcadores/análise , Colletotrichum/fisiologia , Fragaria/microbiologia
19.
J Food Sci ; 84(10): 2805-2811, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31441960

RESUMO

Recently, kaempferol and its glycosides have attracted considerable attention owing to their potentially health-benefitting properties including protection against chronic diseases. Here, a microwave-assisted extraction (MAE) method was developed for the extraction of total flavonoid glycosides (FG) from Camellia oleifera meal, a major agrifood waste largely generated as a byproduct from the Camellia oil processing industry. Compared with traditional extraction methods, MAE enables more efficient extraction of FG. High-speed countercurrent chromatography was then applied to separate FG from MAE extract, and two major compounds were successfully separated with purities above 90.0% as determined by HPLC. These two compounds were further identified by UV, FT-IR, ESI-MS, 1 H-NMR, and 13 C-NMR as kaempferol 3-O-[α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranosyl]-7-O-ß-D-glucopyranoside and kaempferol 3-O-[ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl]-7-O-α-L-rhamnopyranoside, which were for the first time separated from C. oleifera meal. The results of antioxidant activity assay demonstrated that both compounds had excellent scavenging activity for DPPH radical, and exhibited protective effects against H2 O2 -induced oxidative damage of vascular endothelial cells. The findings of this work suggest the possibility of employing C. oleifera meal as an attractive source of health-promoting compounds, and at the same time facilitate its high-value reuse and reduction of environmental burden.

20.
Phys Chem Chem Phys ; 21(33): 18105-18118, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31396604

RESUMO

With the emergence of drug-resistant Plasmodium falciparum, the treatment of malaria has become a significant challenge; therefore, the development of antimalarial drugs acting on new targets is extremely urgent. In Plasmodium falciparum, type II nicotinamide adenine dinucleotide (NADH) dehydrogenase (NDH-2) is responsible for catalyzing the transfer of two electrons from NADH to flavin adenine dinucleotide (FAD), which in turn transfers the electrons to coenzyme Q (CoQ). As an entry enzyme for oxidative phosphorylation, NDH-2 has become one of the popular targets for the development of new antimalarial drugs. In this study, reliable motion trajectories of the NDH-2 complex with its co-factors (NADH and FAD) and inhibitor, RYL-552, were obtained by comparative molecular dynamics simulations. The influence of cofactor binding on the global motion of NDH-2 was explored through conformational clustering, principal component analysis and free energy landscape. The molecular interactions of NDH-2 before and after its binding with the inhibitor RYL-552 were analyzed, and the key residues and important hydrogen bonds were also determined. The results show that the association of RYL-552 results in the weakening of intramolecular hydrogen bonds and large allosterism of NDH-2. There was a significant positive correlation between the angular change of the key pocket residues in the NADH-FAD-pockets that represents the global functional motion and the change in distance between NADH-C4 and FAD-N5 that represents the electron transfer efficiency. Finally, the possible non-competitive inhibitory mechanism of RYL-552 was proposed. Specifically, the association of inhibitors with NDH-2 significantly affects the global motion mode of NDH-2, leading to widening of the distance between NADH and FAD through cooperative motion induction; this reduces the electron transfer efficiency of the mitochondrial respiratory chain. The simulation results provide useful theoretical guidance for subsequent antimalarial drug design based on the NDH-2 structure and the respiratory chain electron transfer mechanism.


Assuntos
Antimaláricos/química , Cetonas/química , NADH Desidrogenase/antagonistas & inibidores , Plasmodium falciparum/enzimologia , Proteínas de Protozoários/antagonistas & inibidores , Proteínas de Protozoários/química , Quinolinas/química , Transporte de Elétrons , Flavina-Adenina Dinucleotídeo/química , Ligações de Hidrogênio , Modelos Moleculares , Estrutura Molecular , NAD/química , NADH Desidrogenase/química , Oxirredução , Ligação Proteica , Relação Estrutura-Atividade , Termodinâmica
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