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1.
Artigo em Inglês | MEDLINE | ID: mdl-32155045

RESUMO

Protein-supported nanoparticles have a great significance in scientific and nanotechnology research because of their "green" process, low cost-in-use, good biocompatibility, and some interesting properties. Ruthenium oxide nanoparticles (RuO2NPs) have been considered to be an important member in nanotechnology research. However, the biosynthetic approach of RuO2NPs is relatively few compared to those of other nanoparticles. To address this challenge, this work presented a new way for RuO2NP synthesis (BSA-RuO2NPs) supported by bovine serum albumin (BSA). BSA-RuO2NPs are confirmed to exert peroxidase-like activity, electrocatalytic activity, in vitro salt resistance (2 M NaCl), and biocompatibility. Results indicate that BSA-RuO2NPs have higher affinity binding for 3,3',5,5'-tetramethylbenzidine or H2O2 than bare RuO2NPs. Moreover, BSA turns out to be a crucial factor in promoting the stability of RuO2NPs. Taking the advantages of these improved properties, we established colorimetric (linear range from 2 to 800 µM, a limit of detection of 1.8 µM) and electrochemical (linear range from 0.4 to 3850 µM, a limit of detection of 0.18 µM) biosensors for monitoring in situ H2O2 secretion from living MCF-7 cells. Herein, this work offers a new biosynthesis strategy to obtain BSA-RuO2NPs and sheds light on the sensitive biosensors to monitor the H2O2 secreted from living cells for promising applications in the fields of nanotechnology, biology, biosensors, and medicine.

2.
Development ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32165490

RESUMO

Vitellogenin receptors (VgRs) play critical roles in oogenesis by mediating endocytosis of vitellogenin and other nutrients in ovipara. We conducted small RNA sequencing and screening with a luciferase reporter system, and found that bmo-miR-2739 and a novel miRNA (novel-miR-167) coordinately regulate the expression of VgR in Bombyx mori (BmVgR). Further analyses suggested that these two miRNAs direct target repression by binding directly to the BmVgR 3' untranslated region. Forced expression of either miRNA using the piggyBac system blocked vitellogenin (Vg) transport and retarded ovariole development. Antagomir silencing of bmo-miR-2739 or novel-miR-167 resulted in increased amounts of BmVgR protein in the ovaries and BmVgR mRNA in the fat body. This evidence combined with spatiotemporal expression profiles revealed that these two miRNAs function together to fine-tune the amount of BmVgR protein for ovarian development. Additionally, novel-miR-167 mainly switched on the posttranscriptional repression of BmVgR in non-ovarian tissues. The results of this study contribute to a better understanding of the function of miRNA during ovarian development of a lepidopteran and suggest a new strategy for controlling insect reproduction.

3.
Lung Cancer ; 142: 13-19, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32062199

RESUMO

OBJECTIVES: This study is aimed to analyze the survival differences among patients with lung basaloid squamous cell carcinoma (BSCC), keratinizing squamous cell carcinoma (KSCC), and nonkeratinizing squamous cell carcinoma (NKSCC), and explore the prognostic factors of patients with lung BSCC. MATERIALS AND METHODS: We searched the information of 4743 patients with lung SCC between 2005 and 2014 from the SEER database. Propensity score matching (PSM) was used to adjust confounding factors. The overall survival (OS), cancer-specific survival (CSS), and cumulative incidence of cancer-specific mortality (CSM) were estimated with a comparative analysis. A competing risks regression model was conducted to identify the prognostic factors of lung BSCC. RESULTS: After PSM, patients with lung BSCC had a higher CSS rate than those with lung KSCC or NKSCC (5-year CSS rate: 50.4 % vs. 37.7 % vs. 38.5 %, p = 0.033 and p = 0.033). The cumulative incidence of CSM was lower for patients with lung BSCC than those with lung KSCC or NKSCC (5-year CSM rate: 46.4 % vs. 56.9 % vs. 56.4 %, p = 0.046 and p = 0.042), which were similar to the results before PSM. As for patients with lung KSCC and NKSCC, there was no survival differences between them (5-year CSS rate: 37.7 % vs. 38.5 %, p = 0.997). The competing risks regression analysis showed that T stage, N stage, M stage and surgery were independent prognostic factors for patients with lung BSCC (all p < 0.05). CONCLUSIONS: Patients with lung BSCC had a better survival than those with lung KSCC or NKSCC, while no survival differences were found between lung KSCC and NKSCC. T stage, N stage, M stage and surgery were independent prognostic factors for patients with lung BSCC.

4.
Aging (Albany NY) ; 12(4): 3298-3311, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32062612

RESUMO

BACKGROUND: Berberine (BBR) has gained considerable attention because of its anti-tumor activity. BBR can induce apoptosis of acute lymphoblastic leukemia (ALL) cells through the MDM2/p53 pathway. However, the effects of BBR on those ALL patients with p53 deficiency remain unclear. RESULTS: We found that BBR reduced ALL cell viability and induced apoptosis in p53-null EU-4 and p53-mutant EU-6 cells by downregulating X-linked inhibitor of apoptosis protein (XIAP), which is increased in ALL tissues and cells. BBR-induced cell apoptosis was attenuated by inhibition of XIAP that was controlled by PIM-2. Mechanistic studies showed that BBR treatment induced an enhancement of miR-24-3p. PIM-2 is a direct target of miR-24-3p. Blockade of PIM-2 or miR-24-3p reversed BBR-induced cell apoptosis. In vivo studies, BBR remarkably alleviated leukemia conditions in a EU4 xenograft mouse model, whereas inhibition of miR-24-3p significantly reversed the effects of BBR in the leukemia condition. CONCLUSIONS: miR-24-3p/PIM-2/XIAP signaling contributes to BBR-mediated leukemia mitigation in p53-defect ALL, which should be further developed as a treatment strategy in ALL patients with p53 deficiency. METHODS: Cell viability and apoptosis were determined using CCK-8 and TUNEL assays, respectively. The dual-luciferase reporter gene system was used to determine the interaction between miR-24-3p and 3'-untranslated regions (UTRs) of PIM-2.

5.
Biomed Pharmacother ; 125: 109836, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32007914

RESUMO

BACKGROUND: Increasing evidence has shown the beneficial effects of Rhodiola species on metabolic disorders, but their mechanisms are not clear. Hepatic steatosis is closely related to metabolic disorders, we aim to investigate the therapeutic effects of Rhodiola crenulata root (RCR) on fructose-induced hepatic steatosis and explore the underlying mechanisms. PURPOSE: To observe the effect of Rhodiola crenulata root extract (RCR) on fructose-induced hepatic steatosis in Sprague-Dawley (SD) rats and explore its possible mechanism. METHODS: Male Sprague-Dawley rats were treated with liquid fructose in their drinking water over 18 weeks. The extract of RCR was co-administered (once daily by oral gavage) during the last 5 weeks. Liver lipid deposition and morphological changes were observed by Oil red O staining. Real-time fluorescence quantitative PCR, Western blot and immunoprecipitation were used to detect gene and protein expression in liver. RESULTS: RCR (50 mg/kg) reversed liquid fructose-induced increase in hepatic triglyceride content in rats. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in RCR-treated rats. However, RCR treatment did not affect chow intake and body weight of rats. Although some genes of the pathways involved in DNL (ChREBP, SREBP-1c, FAS, ACC1, SCD1, DGAT1, DGAT2 and MGAT2), fatty acid ß-oxidation (PPARα, CPT1a, ACO and FGF21), VLDL-export (MTTP) and decomposition (HSL, ATGL) in the liver of fructose-fed rats were not changed significantly after RCR administration, the decrease in PPARα and PGC-1α proteins was reversed by RCR. Notably, SIRT1 mRNA and protein expression increased significantly with RCR administration. Furthermore, RCR increased expression of ATG4B, Beclin1 and decreased expression of Bcl2-Beclin1 complex dramatically. Meanwhile, RCR decreased the acetylation of beclin1. Moreover, RCR increased expression of autophagosome markers including LC3B and ATG5-ATG12-ATG16L1, and decreased expression of autophagolysosome marker p62 in the livers of fructose-fed rats. CONCLUSIONS: RCR has a certain improvement effect on fructose-induced hepatic steatosis, which is related to the activation of autophagy.

6.
PLoS One ; 15(1): e0220482, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31986139

RESUMO

The common long-armed octopus, Octopus minor, is an important component of systems and supports the local fisheries in the coastal areas of northern China. For the fishery management and artificial breeding, especially for the management of exclusive conservation reserves, its role in the ecosystem requires assessment. Therefore, the feeding intensity of O. minor was studied from April to July 2014 when females reaching ovary maturation, and prey composition was identified from stomach contents using a DNA barcoding method. Of the 172 sampled octopuses, 66 had stomach contents that were nearly digested into pulp. On the whole, the feeding intensity of octopus remained more or less the same during the first three months and significantly decreased in July. The changes of feeding intensity were different between females and males; in females, the intensity of feeding decreased from April to July; in case of males, however, the feeding activity increased from April to June and decreased thereafter. The feeding intensity of the females was extremely greater than that of the males. O. minor was a generalist predator and based on homology searches and phylogenetic analysis, a total of 10 different taxa were identified in the stomach contents. In terms of percent composition by frequency of occurrences (%N), fishes accounted for the most of the octopuses diet (50%), followed by cephalopod (25%), crustaceans (21.7%), annelid (1.7%) and nematode (1.7%). The families of Gobiidae and Octopodidae appeared in all months and Protunidae appeared in three months. The results confirmed that Gobiidae family (45.8%, by frequency of occurrences) was an important source of food during the time when females reaching ovarian maturation. From April to July, the observed cannibalism showed an increasing trend. Controlling and reducing fishing production of Gobiidae fishes in conservation area are recommended from April to June when female octopuses are actively feeding.

7.
J Cell Mol Med ; 24(5): 3167-3182, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31991051

RESUMO

OBJECTIVES: Investigation of mechanism related to excessive invasion of trophoblast cells in placenta accreta spectrum disorders (PAS) provides more strategies and ideas for clinical diagnosis and treatment. MATERIALS AND METHODS: Blood and placental samples were collected from included patients. The distribution and expression of CXCL12, CXCR4 and CXCR7 proteins in the paraffin of placental tissue in the included cases were analysed, and we analyse the downstream pathways or key proteins involved in cell invasion. RESULTS: Firstly, our results determined that CXCL12 and CXCR4/CXCR7 were increased in extravillous trophoblastic cell (CXCL12: P < .001; CXCR4: P < .001; CXCR7: P < .001), and the expression levels were closely related to the invasion depth of trophoblastic cells. Secondly, CXCL12 has the potential to become a biochemical indicator of PAS since the high expression of placental trophoblast CXCL12 may be an important source of blood CXCL12. Using lentivirus-mediated RNA interference and overexpression assay, it was found that both chemokine CXCL12 and receptor CXCR4/CXCR7 are associated with regulation of trophoblast cell proliferation, migration and invasion. Further results proved that through the activating the phosphorylation and increasing the expression of MLC and AKT proteins in the Rho/rock, PI3K/AKT signalling pathway, CXCL12, CXCR4 and CXCR7 could up-regulate the expression of RhoA, Rac1 and Cdc42 proteins to promote the migration and invasion of extravillous trophoblastic cell and ultimately formate the placenta accrete compare to the normal placenta. CONCLUSIONS: Our research proved that trophoblasts may contribute to a PAS-associated increase in CXCL12 levels in maternal blood. CXCL12 is not only associated with biological roles of PAS, but may also be potential for prediction of PAS.

8.
JAMA Dermatol ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31895418

RESUMO

Importance: Integrated information on the global prevalence and incidence of oral lichen planus (OLP) is lacking. Objective: To examine the global prevalence and incidence of OLP in a systematic review and meta-analysis. Data Sources: A systematic review of population-based studies and clinic-based studies reporting the prevalence and incidence of OLP was performed using 3 electronic medical databases (Cochrane Database of Systematic Reviews, Embase, and MEDLINE) from their inception to March 2019. The search terms included "(lichen planus or LP) and (prevalence or incidence or epidemiology)." No language restriction was applied. Study Selection: Observational descriptive studies investigating the prevalence and incidence of OLP were included. Data Extraction and Synthesis: Data were extracted by continent, sex, and other characteristics. The risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence. Main Outcomes and Measures: The primary outcome was the prevalence (with 95% CIs) of OLP among the overall population and among subgroups. Between-study heterogeneity was assessed using the I2 statistic. Results: Among 46 studies, the overall pooled estimated prevalence of OLP was 0.89% (95% CI, 0.38%-2.05%) among the general population (n = 462 993) and 0.98% (95% CI, 0.67%-1.43%) among clinical patients (n = 191 963). Among the 15 population-based studies, the prevalence of OLP was 0.57% (95% CI, 0.15%-2.18%) in Asia, 1.68% (95% CI, 1.09%-2.58%) in Europe, and 1.39% (95% CI, 0.58%-3.28%) in South America. Among the 31 clinic-based studies, the prevalence was 1.43% (95% CI, 1.12%-1.83%) in Africa, 0.87% (95% CI, 0.61%-1.25%) in Asia, 1.03% (95% CI, 0.51%-2.09%) in Europe, 0.11% (95% CI, 0.07%-0.16%) in North America, and 3.18% (95% CI, 0.97%-9.95%) in South America. The pooled prevalence of OLP by sex was 1.55% (95% CI, 0.83%-2.89%) for women and 1.11% (95% CI, 0.57%-2.14%) for men in the population-based studies and 1.69% (95% CI, 1.05%-2.70%) for women and 1.09% (95% CI, 0.67%-1.77%) for men in the clinic-based studies. In 5 clinic-based studies providing the age distribution of patients with OLP, the prevalence by age was 0.62% (95% CI, 0.33%-1.13%) among patients younger than 40 years and 1.90% (95% CI, 1.16%-3.10%) among patients 40 years and older. Conclusions and Relevance: This study identified the global prevalence and incidence of OLP in terms of its spatial, temporal, and population distribution. The overall estimated pooled prevalence of OLP was 0.89% among the general population and 0.98% among clinical patients. A higher prevalence of OLP was found in non-Asian countries, among women, and among people 40 years and older. The findings should be considered with caution because of the high heterogeneity of the included studies.

9.
Comput Methods Biomech Biomed Engin ; 23(4): 127-137, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31931606

RESUMO

We established an effective finite element model of knee joint for observation of stress and displacement of meniscus related changes after medial meniscus injury. Different types of medial meniscus injury can lead to varied meniscus stress and displacement changes. Stress and displacement concentration were found in fissure tip of meniscus tear compared to normal meniscus. The posterior horn injury of medial meniscus may initiate combined injury of medial meniscus posterior horn (MMPH) and that of medial meniscus body, and combined injury of MMPH and that of lateral meniscus anterior horn; fissure expansions regarding horizontal fissure, longitudinal fissure and grip-shaped fissure of MMPH were spotted.

10.
Cancer Biol Ther ; 21(4): 309-314, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959056

RESUMO

Acute promyelocytic leukemia (APL) is characterized by the presence of promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion gene, which is formed following the specific chromosomal translocation t(15;17)(q22;q21). However, cases with PML-RARα generated by occult t(15;17) which are negative by both cytogenetics and fluorescence in situ hybridization (FISH), are difficult to diagnose, leading to impaired treatment effectiveness. In the present study, we reported a case of a 66-year-old male patient, and bone marrow morphology, flow cytometry and cytogenetics did not support the diagnosis of APL. Molecular techniques, such as reverse-transcription polymerase chain reaction (RT-PCR), showed the existence of a cryptic PML-RARα fusion gene, and sequence analysis revealed a new variable isoform. Hotspot gene mutation analysis showed a biallelic CEBPA mutation. He received IA chemotherapy and all-trans retinoic acid (ATRA) treatment, and finally achieved complete remission. This case report provided valuable insights into the relevance of the correct identification of atypical PML-RARα fusion gene and biallelic CEBPA mutation. Moreover, combination of IA chemotherapy and ATRA treatment suggested a good clinical effect in this atypical PML-RARα.

11.
J Cosmet Dermatol ; 19(1): 10-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654468

RESUMO

BACKGROUND: Photodynamic therapy (PDT) has emerged as the effective new method to treat acne vulgaris. However, no meta-analysis has been published on PDT for acne vulgaris currently. OBJECTIVE: The current meta-analysis and systematic review were carried out to assess the safety and effect of PDT on treating acne vulgaris. METHODS: The electronic databases, including EMBASE, Cochrane Library, and MEDLINE, were systemically retrieved to identify relevant articles for meta-analysis. The primary outcome included mean percentage reduction in the inflammatory lesion count (MPRILC), while the secondary outcome included the total effective response (TER). RESULTS: Altogether 13 randomized controlled trials (RCTs) involving 701 subjects had been enrolled into the current meta-analysis. PDT had certain effect on acne vulgaris in terms of the outcomes of MPRILC (MD: 15.97, 95% CI: 11.93 to 20.00, P < .00001) and TER (RR: 1.55, 95% CI: 1.38-1.74, P < .00001). Totally, 6 articles had been evaluated to have a low bias risk overall. Results of sensitivity and subgroup analyses were similar to meta-analysis results, reflecting the result reliability in this meta-analysis. CONCLUSIONS: PDT is beneficial for improving the clinical efficacy of inflammatory acne vulgaris, which can be widely used to treat inflammatory acne vulgaris in clinic.

12.
Gut ; 69(2): 365-379, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31076403

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC), mostly developed in fibrotic/cirrhotic liver, exhibits relatively low responsiveness to immune checkpoint blockade (ICB) therapy. As myeloid-derived suppressor cell (MDSC) is pivotal for immunosuppression, we investigated its role and regulation in the fibrotic microenvironment with an aim of developing mechanism-based combination immunotherapy. DESIGN: Functional significance of MDSCs was evaluated by flow cytometry using two orthotopic HCC models in fibrotic liver setting via carbon tetrachloride or high-fat high-carbohydrate diet and verified by clinical specimens. Mechanistic studies were conducted in human hepatic stellate cell (HSC)-peripheral blood mononuclear cell culture systems and fibrotic-HCC patient-derived MDSCs. The efficacy of single or combined therapy with anti-programmed death-1-ligand-1 (anti-PD-L1) and a clinically trialled BET bromodomain inhibitor i-BET762 was determined. RESULTS: Accumulation of monocytic MDSCs (M-MDSCs), but not polymorphonuclear MDSCs, in fibrotic livers significantly correlated with reduced tumour-infiltrating lymphocytes (TILs) and increased tumorigenicity in both mouse models. In human HCCs, the tumour-surrounding fibrotic livers were markedly enriched with M-MDSC, with its surrogate marker CD33 significantly associated with aggressive tumour phenotypes and poor survival rates. Mechanistically, activated HSCs induced monocyte-intrinsic p38 MAPK signalling to trigger enhancer reprogramming for M-MDSC development and immunosuppression. Treatment with p38 MAPK inhibitor abrogated HSC-M-MDSC crosstalk to prevent HCC growth. Concomitant with patient-derived M-MDSC suppression by i-BET762, combined treatment with anti-PD-L1 synergistically enhanced TILs, resulting in tumour eradication and prolonged survival in the fibrotic-HCC mouse model. CONCLUSION: Our results signify how non-tumour-intrinsic properties in the desmoplastic microenvironment can be exploited to reinstate immunosurveillance, providing readily translatable combination strategies to empower HCC immunotherapy.


Assuntos
Carcinoma Hepatocelular/terapia , Imunoterapia/métodos , Neoplasias Hepáticas/terapia , Animais , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/imunologia , Reprogramação Celular/imunologia , Ciclopropanos/farmacologia , Ciclopropanos/uso terapêutico , Células Estreladas do Fígado/imunologia , Humanos , Tolerância Imunológica , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas Experimentais/etiologia , Neoplasias Hepáticas Experimentais/imunologia , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas Experimentais/terapia , Masculino , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Células Supressoras Mieloides/imunologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Transdução de Sinais/fisiologia , Células Tumorais Cultivadas , Microambiente Tumoral , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia
13.
J Dermatolog Treat ; 31(1): 77-83, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702958

RESUMO

Background: Treatment of melasma is challenging because its pathogenesis is unclear and it is prone to recurrence. We performed a meta-analysis to evaluate the efficacy and safety of laser and laser compound therapy for melasma.Methods: We searched the Cochrane, Embase, and Medline databases for all relevant studies published from inception to July 2018. All randomized controlled trials of melasma describing treatment with lasers or laser compound therapy were included.Results: A total of 346 patients were enrolled in nine RCT studies. Laser therapy and laser compound therapy had better PGA (MD: 1.96 (95% CI: 0.17, 3.75); I2 = 0%) and mMASI scores (MD: -1.57 (95% CI: -3.08, -0.05); I2 = 19%) than drug and laser therapy, respectively. Four studies were assessed to be of low risk of bias. Subgroup analysis was consistent with the results of the meta-analysis, reflecting the reliability of our results.Linking evidence to action: The results of this meta-analysis provide evidence that laser and laser compound therapy can improve the area and severity of melasma. Further high-quality clinical studies should be carried out in the future to confirm this conclusion. Abbreviations: MASI: Melasma Area and Severity Index; mMASI: modified Melasma Area and Severity Index; PGA: patient global assessment; MI: melasma index.

14.
Talanta ; 208: 120359, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816689

RESUMO

A versatile protocol has been developed for highly sensitive magnetic relaxation detection of the analyte based on the fabrication of MnO nanoparticles (NPs) assemblies. Based on the strategy that positively charged analyte could induce the assembly of negatively charged MnO NPs through electrostatic interaction, which will generate the change of magnetic relaxation rate of MnO NPs, we achieved highly sensitive and convenient detection of the analytes. By applying the detection of melamine as an example, we found that the detection limit can be as low as 0.733 ppb. Furthermore, this strategy has been applied for the initially detection of commercially available milk spiked with melamine as proof of its potential applicability of detection in complicated food samples.

15.
Plant Signal Behav ; 15(1): 1706025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31851568

RESUMO

OsCASP1 (Casparian strip domain protein 1) was recently identified to function in Casparian strip (CS) formation at the endodermal cells in rice roots, which was required for selective mineral uptake in rice. Here, we further investigate the functional form of OsCASP1 in vivo. Expression analysis shows that OsCASP1, OsCASP2, OsCASP3, and OsCASP5 were expressed in roots apart from OsCASP4. A yeast two-hybrid (Y2H) assay revealed that OsCASP1 can interact with itself and OsCASP2, but not with OsCASP3 and OsCASP5. These interactions of OsCASP1 with itself and OsCASP2 at the plasma membrane were confirmed using bimolecular fluorescence complementation (BiFC) in rice protoplasts. These results indicated that OsCASP1 can form complexes with itself and OsCASP2 in rice roots.

16.
Sci Rep ; 9(1): 18035, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792294

RESUMO

Activity in trypsin-like proteases is the result of proteolytic cleavage at R15 followed by an ionic interaction that ensues between the new N terminus of I16 and the side chain of the highly conserved D194. This mechanism of activation, first proposed by Huber and Bode, organizes the oxyanion hole and primary specificity pocket for substrate binding and catalysis. Using the clotting protease thrombin as a relevant model, we unravel contributions of the I16-D194 ionic interaction to Na+ binding, stability of the transition state and the allosteric E*-E equilibrium of the trypsin fold. The I16T mutation abolishes the I16-D194 interaction and compromises the architecture of the oxyanion hole. The D194A mutation also abrogates the I16-D194 interaction but, surprisingly, has no effect on the architecture of the oxyanion hole that remains intact through a new H-bond established between G43 and G193. In both mutants, loss of the I16-D194 ionic interaction compromises Na+ binding, reduces stability of the transition state, collapses the 215-217 segment into the primary specific pocket and abrogates the allosteric E*-E equilibrium in favor of a rigid conformation that binds ligand at the active site according to a simple lock-and-key mechanism. These findings refine the structural role of the I16-D194 ionic interaction in the Huber-Bode mechanism of activation and reveal a functional linkage with the allosteric properties of the trypsin fold like Na+ binding and the E*-E equilibrium.

17.
Molecules ; 24(24)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817679

RESUMO

The root of Gentiana straminea Maxim. (Gentianaceae), is officially listed as "Qin-Jiao" in the Chinese Pharmacopoeia for the treatment of rheumatic arthritis, icteric hepatitis, constipation, pain, and hypertension. To establish the geographical origin traceability in G. straminea, its chemical profiles were determined by a UPLC-Q exactive mass spectrometer, from which 43 compounds were identified by comparing retention times and mass spectrometry. Meanwhile, a pair of isomers (loganin and secologanol) was identified by mass spectrometry based on their fragmentation pathway. A total of 42 samples from difference habitats were determined by an UPLC-Q exactive mass spectrometer and the data were assayed with multivariate statistical analysis. Eight characteristic compounds were identified to determine the geographical origin of the herb. To estimate the key characteristic markers associated with pharmacological function, the inhibiting activities of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages were examined. This finding is crucial in realizing the determination of botanical origin and evaluating the quality of G. straminea.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31786623

RESUMO

PURPOSE: This study was undertaken to elucidate the clinical significance of widening of the popliteal hiatus on magnetic resonance imaging (MRI), and to document the clinical results and technical aspects of arthroscopic repair of this finding. METHODS: Included are 82 knees after arthroscopic surgery, divided according to arthroscopic diagnosis into group A, hypermobility of lateral meniscus, 8 knees; group B, tear of the anterior horn of the lateral meniscus, 32 knees; and group C, no abnormality of the lateral meniscus, 36 knees with medial meniscal tears and 6 with other conditions. Popliteal hiatus diameter was measured and the popliteal hiatus/lateral tibial plateau (LTP) ratio was calculated on preoperative sagittal and coronal MRI. At arthroscopy, the widened popliteal hiatus in group A was tightened anteriorly by outside-in or all-inside suture and posteriorly with all-inside suture. Outcomes were evaluated with MRI, Lysholm, Tegner and VAS scores. RESULTS: The preoperative diameter of the popliteal hiatus and the popliteal hiatus/LTP ratio were significantly larger in group A than in groups B and C (p < 0.05) on both views. Threshold popliteal hiatus/LTP values of 0.16 and 0.18 on the sagittal and coronal views demonstrated diagnostic discrimination, and these values were significantly reduced after arthroscopy in Group A. Lysholm and Tegner scores were improved after tightening of the popliteal hiatus, while VAS scores reduced (all p < 0.05). CONCLUSION: Widening of the popliteal hiatus on MRI may lead to recurrent subluxation of the lateral meniscus. Arthroscopic anterior and posterior tightening of the popliteal hiatus was a safe and effective treatment. LEVEL OF EVIDENCE: II.

20.
Drug Chem Toxicol ; : 1-8, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31665937

RESUMO

Salusin-α is a bioactive peptide that protects against atherosclerosis and hepatosteatosis. Serum salusin-α level is declined in patients suffering with renal insufficiency. However, it is still undefined whether salusin-α plays a role in diabetic nephropathy. The present study was designed to investigate the potential roles of salusin-α in diabetic renal disease. Herein, we demonstrated that the salusin-α levels in both plasma and kidney tissues from diabetic rats were obviously downregulated. Exogenous administration of salusin-α eliminated the typical characteristics of diabetic nephropathy. Salusin-α treatment decreased renal fibrosis, which was related with reduced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Injection of salusin-α suppressed the production of reactive oxygen species (ROS) via attenuation of NADPH oxidase subunits protein expressions and recovery of the antioxidant system. Mechanistically, the activated Akt/mTORC1/p70S6K signaling pathway in diabetic nephropathy was counteracted by salusin-α treatment. Our results demonstrated that salusin-α exerted protective effect against diabetic nephropathy via reduced oxidative stress and fibrosis, dependent on inactivation of the Akt/mTORC1/p70S6K signaling cascade. Salusin-α may be considered as a promising target for the treatment of diabetic nephropathy.

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