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1.
Eur Radiol ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350658

RESUMO

OBJECTIVES: To build models based on conventional logistic regression (LR) and machine learning (ML) algorithms combining clinical, morphological, and hemodynamic information to predict individual rupture status of unruptured intracranial aneurysms (UIAs), afterwards tested in internal and external validation datasets. METHODS: Patients with intracranial aneurysms diagnosed by computed tomography angiography and confirmed by invasive cerebral angiograph or clipping surgery were included. The prediction models were developed based on clinical, aneurysm morphological, and hemodynamic parameters by conventional LR and ML methods. RESULTS: The training, internal validation, and external validation cohorts were composed of 807 patients, 200 patients, and 108 patients, respectively. The area under curves (AUCs) of conventional LR models 1 (clinical), 2 (clinical and aneurysm morphological), and 3 (clinical, aneurysm morphological and hemodynamic characteristics) were 0.608, 0.765, and 0.886, respectively (all p < 0.05). The AUCs of ML models using random forest (RF), multilayer perceptron (MLP), and support vector machine (SVM) were 0.871, 0.851, and 0.863, respectively. There were no difference among AUCs of conventional LR, RF, and SVM (all p > 0.05/6), while the AUC of MLP was lower than that of conventional LR (p = 0.0055). CONCLUSION: Hemodynamic parameters play an important role in the prediction performance of the models. ML methods cannot outperform conventional LR in prediction models for rupture status of UIAs integrating clinical, aneurysm morphological, and hemodynamic parameters. KEY POINTS: • The addition of hemodynamic parameters can improve prediction performance for rupture status of unruptured intracranial aneurysms. • Machine learning algorithms cannot outperform conventional logistic regression in prediction models for rupture status integrating clinical, aneurysm morphological, and hemodynamic parameters. • Models integrating clinical, aneurysm morphological, and hemodynamic parameters may help choose the optimal management.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32356196

RESUMO

Basidioma is the fruiting body of mushroom species. The deep understanding on the mechanism of basidioma development is valuable for mushroom breeding and cultivation. From winter mushroom (Flammulina velutipes), one of the top five industrially cultivated mushrooms, a novel putative Zn(II)2Cys6 transcription factor LFC1 with negative regulatory function in basidioma development was identified. The transcript level of lfc1 was dramatically decreased during basidioma development. Neither overexpression nor knockdown of lfc1 affected hyphal vegetative growth. However, knockdown of lfc1 could promote basidioma development and shorten cultivation time by 2 days, while overexpression of lfc1 delayed the optimal harvest time by 3 days. In the lfc1 knockdown strain, in which the lfc1 expression was reduced by 72%, mushroom yield and biological efficiency could be increased at least by 24%. Knockdown of lfc1 did not affect the shape of caps but significantly increased basidioma length and number, while its overexpression did not affect basidioma length but dramatically reduced basidioma number. In addition, rather than producing basidiomata with round caps as in wild type, the caps of basidiomata in the lfc1 overexpression mutants were significantly larger and the cap edge was wrinkled. RNA-seq analysis revealed that 455 genes had opposite transcriptional responses to lfc1 overexpression and knockdown. Some of them were previously reported as genes involved in basidioma development, including 3 hydrophobin encoding genes, 2 lectin encoding genes, FVFD16, an Eln2 ortholog encoding gene, and 3 genes encoding membrane components. As LFC1 homologs are widely present in mushroom species, lfc1 can be useful in mushroom breeding.Key Points• A novel transcription factor LFC1 negatively regulates fruiting in winter mushroom• LFC1 regulated transcription of more than 400 genes.• Reduction of LFC1 expression could shorten cultivation time and increase yield.• lfc1 could be a potentially useful reference gene for mushroom breeding.

3.
Nat Prod Res ; : 1-11, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375507

RESUMO

Five new lignans, euphorhirtins A-D (1-4), 5-methoxyvirgatusin (5), three artefacts, 7S-ethoxyisolintetralin (6), 7R-ethoxyisolintetralin (7), and 7R-ethoxy-3-methoxyisolintetralin (8), together with 13 known ones (9-21) were isolated from the medicinal plant Euphorbia hirta L. The structures of the compounds were elucidated by means of extensive spectroscopic analysis, including 1D and 2D NMR and HR-ESI-MS experiments. The absolute configurations of compound 1 was determined by ECD calculation. The isolates were evaluated for their inhibitory effects against the proliferation of the cancer cell lines (Hep G2, A549, and DU145) and compounds 14 and 18 showed inhibitory activity against the Hep G2 cells with IC50 values 7.2 ± 0.17 and 8.5 ± 0.36 µM.

4.
J Thorac Imaging ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32366759

RESUMO

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has spread rapidly throughout China and other countries, and has been characterized as a pandemic. With the strict prevention and control measures implemented by the Chinese government, the spread of the epidemic in China has come under preliminary control by the end of February, 2020, whereas the situation of some countries outside China is not optimistic and raises great public concern. In fighting COVID-19, radiologic examinations played a critical role in the early diagnosis of COVID-19, and could also help assess disease course and severity. There is an urgent need to share useful experience and effective measures internationally. This article outlines the collaborative actions and efforts by the Chinese radiology field and the situation of front-line health care workers in radiology departments to present the world with experiences and examples of Chinese radiology during the COVID-19 outbreak.

5.
Int J Mol Sci ; 21(9)2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32370225

RESUMO

The endometrium is an important tissue for pregnancy and plays an important role in reproduction. In this study, high-throughput transcriptome sequencing was performed in endometrium samples of Meishan and Yorkshire pigs on days 18 and 32 of pregnancy. Aldo-keto reductase family 1 member C1 (AKR1C1) was found to be a differentially expressed gene, and was identified by quantitative real-time PCR (qRT-PCR) and Western blot. Immunohistochemistry results revealed the cellular localization of the AKR1C1 protein in the endometrium. Luciferase activity assay demonstrated that the AKR1C1 core promoter region was located in the region from -706 to -564, containing two nuclear factor erythroid 2-related factor 2 (NRF2) binding sites (antioxidant response elements, AREs). XLOC-2222497 was identified as a nuclear long non-coding RNA (lncRNA) highly expressed in the endometrium. XLOC-2222497 overexpression and knockdown have an effect on the expression of AKR1C1. Endocrinologic measurement showed the difference in progesterone levels between Meishan and Yorkshire pigs. Progesterone treatment upregulated AKR1C1 and XLOC-2222497 expression in porcine endometrial epithelial cells. In conclusion, transcriptome analysis revealed differentially expressed transcripts during the early pregnancy process. Further experiments demonstrated the interaction of XLOC-2222497/AKR1C1/progesterone in the endometrium and provided new potential targets for pregnancy maintenance and its control.

6.
J Affect Disord ; 273: 32-40, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32421620

RESUMO

BACKGROUND: FK506 binding protein 5 (FKBP5) rs1360780 polymorphism has been identified as a molecular genetic marker associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The impact of FKBP5 rs1360780 on the large-scale brain network connectivity in healthy adults is still unknown. METHODS: 479 healthy volunteers (age: 20-80years) completed MRI scans, neuropsychological assessments and blood analysis.All subjects were divided into CC, CT and TT genotypes. Within and between network connectivities (10 sub-networks) were calculated using resting state functional MRI (rs-fMRI) data. The genetic effects and gene-gender/age interaction on large-scale network connectivity were explored. RESULTS: Compared with CC and CT groups, TT group showed increased intra-connectivity in default mode network (DMN) and increased inter-connectivity mainly distributed among the network of DMN, salience network (SAN), dorsal attention network (DAN), ventral attention network (VAN), subcortical network (SUB), and visual network (VIS). Gene-by-gender and gene-by-age interaction were found in inter-connectivity of DAN to VIS and DMN to FPN, respectively. The altered connectivities correlated with anxiety status test score. LIMITATIONS: Plasma adrenocorticotropic hormone (ACTH) or cortisol were not measured,or else, we could estimate the hypothalamic-pituitary-adrenal (HPA) axis activity which may strengthen our results. CONCLUSIONS: FKBP5 rs1360780 modulates the large-scale brain network connectivity in healthy adults. TT carriers showed the increased intra- and inter-connectivities mainly distributed among the network of DMN, SAN, DAN, VAN, SUB and VIS.

7.
Clin Chim Acta ; 508: 54-60, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32423860

RESUMO

BACKGROUND: DNA methylation plays an important role in the initiation and progression of colon cancer. The aim of the present study was to perform a comprehensive analysis of DNA methylation and gene expression profiles in order to develop a signature to predict recurrence-free survival (RFS) of colon cancer. METHODS: DNA methylation and mRNA expression data were obtained from TCGA database, and were analyzed using an R package MethylMix. Functional enrichment analysis was performed on statistically significant genes identified by MethylMix criteria. The epigenetic signature and nomogram associated with the RFS of colon cancer were established by the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. Additionally, a joint survival analysis of gene expression and methylation was performed to identify potential prognostic factors for patients with colon cancer. RESULTS: A total of 179 differentially methylated genes were obtained using MethylMix algorithm. An epigenetic signature for RFS was developed using LASSO. Patients with high-risk had significantly worse RFS than those with low-risk. The signature is independent of clinicopathological variables and indicated better predictive power than other clinicopathological variables in patients with colon cancer. Moreover, joint survival analysis of gene expression and methylation revealed that seven methylated genes could be independent prognostic factors for RFS in colon cancer. CONCLUSIONS: Our proposed epigenetic signature presents potential prognostic significance in assessing recurrence risk stratification for patients with colon cancer.

8.
Oral Dis ; 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32267053

RESUMO

Oral squamous cell carcinoma (OSCC) is an extremely aggressive neoplasm, which is usually diagnosed in the advanced stage of the disease. Extensive studies have shown a link between chronic inflammation and various types of cancer, including OSCC. Salicylate is a biotransformation product of aspirin, with similar anti-inflammatory ability to aspirin but lacks aspirin's inhibitory effect on the isolated cyclooxygenase activity. Our study indicates that salicylate sensitizes OSCC to anti-cancer drugs, but the mechanisms of its action are unclear. Here, OSCC cells were used to evaluate the cytotoxicity of salicylate alone or in combination with cisplatin (CDDP). RPPA proteomic array and Western blotting were employed to determine the signaling pathways affected by salicylate. Salicylate decreased cell survival rate and induced cell apoptosis in OSCC cells but not human normal oral mucosal epithelial cells (hTERT-OME). The use of sodium salicylate (SS) dramatically sensitized OSCC cells to CDDP. RPPA array showed that SS reduced many oncogenes such as PI3K/mTOR signaling and cancer stem cell (CSC)-related genes versus control. Western and transcriptional analyses substantiated that salicylate down-regulated these CSC-associated genes and the mTOR pathway dose dependently. Salicylate preferentially repressed the ability of sorted ALDH1+ cells to form tumor spheres. Finally, salicylate suppressed tumor growth in vivo, and the combination of salicylate and CDDP further synergistically reduced the growth of tumors. Salicylate hinders OSCC cell growth and sensitizes OSCC cells to CDDP through targeting CSCs and the mTOR signaling pathway. We propose that salicylate is beneficial for OSCC patients, and salicylate may be combined with chemotherapies to effectively treat OSCC patients.

9.
Indoor Air ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249960

RESUMO

We sought to investigate the association between active cigarette smoking (ex- and current smokers) with or without exposure to biomass fuels and respiratory symptoms/lung function in middle-aged adults and the elderly. In the chronic obstructive pulmonary disease surveillance conducted in six cities of Guangdong province, China, we surveyed 1986 residents aged 40-93 years. We recorded respiratory symptoms, smoking status, use of biomass fuel, and other covariates by using a structured questionnaire. All models were adjusted for second-hand smoking. Active smoking with or without exposure to biomass fuels was significantly associated with wheezing, chronic cough, and phlegm (all P < .05). Active smoking alone with or without exposure to biomass fuels was associated with 2.5% and 0.6% reduction in the mean forced vital capacity predicted, 6.8% and 4.2% reduction in the mean forced expiratory volume in one second predicted, and 9.0% and 4.7% reduction in the mean maximal mid-expiratory flow predicted compared with the exposure to neither smoking nor biomass fuels, respectively. However, exposure to biomass fuel alone was associated with neither greater lung function impairment nor respiratory symptoms except for chronic cough. Efforts should be made to protect home owners and their family from adverse effects of indoor air pollution.

10.
Braz J Med Biol Res ; 53(5): e9331, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348426

RESUMO

The melamine and cyanuric acid (CA) complex has been suggested to cause the toxic effects observed in melamine-contaminated food or milk. However, the cytotoxic and genotoxic effects of co-exposure to melamine and CA are not fully clear. Therefore, the cytotoxic effects of melamine and CA were first examined by co-exposure in human kidney 293 cells using the MTT assay. During a 24-h period for the three concentrations tested (0.5, 1, and 5 mg/mL), neither melamine nor CA alone showed significant toxic effects on 293 cells at 0.5 mg/mL, while higher concentrations led to decreased in cell viability. However, co-exposure to several combinations of melamine and CA [100:1, 10:1, 1:10, and 1:100 (v:v), at a final concentration of 0.5 mg/mL] did cause cytotoxicity with higher levels of CA leading to higher cytotoxicity. By contrast, while neither melamine nor CA alone induced phosphorylated-H2AX (γH2AX) foci formation, melamine and CA at a 100:1 ratio induced γH2AX foci 24 h post-treatment. The alkaline comet assay also revealed the presence of DNA damage following melamine and CA co-exposure. In vivo assay also revealed the presence of melamine-CA complex in the kidney. These data indicated that the cytotoxic and genotoxic effects of melamine and CA co-exposure differ from those of melamine or CA alone.

11.
Fitoterapia ; 143: 104599, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32330576

RESUMO

One novel polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid metabolite, laricinin A (1), two new meroterpenoids, tricycloalternarenes X and Y (2 and 3), one new coumarin, 3,4,7-trihydroxy-6-methylcoumarin (4), together with the known ethyl acetylorsellinate (5), diorcinol K (6), and tricycloalternarenes C and D (7 and 8) were obtained from culture of the fungus Botrysphaeria laricina isolated from the moss Rhodobryum umgiganteum. The structures of the new compounds were elucidated based on extensive spectroscopic techniques including HRMS and 1D and 2D NMR measurements. The absolute configuration of compound 1 was determined by ECD calculation and it was the first example of a novel group of PKS-NRPS hybrids possessing an unprecedented methyldihydropyran-isobutylpyrrolidinone skeleton. Compounds 2, 7, and 8 showed significant quinone reductase inducing activity in Hepa 1c1c7 cells.

12.
J Am Chem Soc ; 142(15): 7190-7197, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32223154

RESUMO

Two new highly charged [2]catenanes-namely, mHe[2]C·6PF6 and mHo[2]C·6PF6-were synthesized by exploiting radical host-guest templation between derivatives containing BIPY•+ radical cations and the meta analogue of cyclobis(paraquat-p-phenylene). In contrast to related [2]catenanes that have been isolated as air-stable monoradicals, both mHe[2]C·6PF6 and mHo[2]C·6PF6 exist as air-stable singlet bisradicals, as evidenced by both X-ray crystallography in the solid state and EPR spectroscopy in solution. Electrochemical studies indicate that the first two reduction peaks of these two [2]catenanes are shifted significantly to more positive potentials, a feature which is responsible for their extraordinary stability in air. The mixed-valence nature of the mono- and bisradical states endows them with unique NIR absorption properties, e.g., NIR absorption bands for the mono- and bisradical states observed at ∼1800 and ∼1450 nm, respectively. These [2]catenanes are potentially useful in applications that include NIR photothermal conversion, UV-vis-NIR multiple-state electrochromic materials, and multiple-state memory devices. Our findings highlight the principle of "mechanical-bond-induced stabilization" as an efficient strategy for designing persistent organic radicals.

13.
Pestic Biochem Physiol ; 164: 173-182, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32284124

RESUMO

Athetis lepigone (Alep) is a polyphagous pest native to Europe and Asia that has experienced major outbreaks in the summer maize area of China since 2011 and has shown evidence of resistance to some insecticides. Insect olfaction is crucial for recognition of sex pheromones, host plant volatiles and even insecticides, in which two general-odorant binding proteins (GOBPs) play important roles. To elucidate the functions of GOBPs in A. lepigone, we first expressed the two AlepGOBP proteins in the E. coli expression system. Then, the results of fluorescence competitive binding assays demonstrated that the high binding affinity of AlepGOBP2 with sex pheromones [(Z)-7-dodecenyl acetate (Z7-12:Ac), Ki = 0.65 µM; (Z)-9-tetradecenyl acetate (Z9-14:Ac), Ki = 0.83 µM], two maize plant volatiles [Ocimene, Ki = 9.63 µM; (E)-ß-Farnesene, Ki = 4.76 µM] and two insecticides (Chlorpyrifos Ki =5.61 µM; Phoxim, Ki = 4.38 µM). However, AlepGOBP1 could only bind Ocimene (Ki = 13.0 µM) and two insecticides (Chlorpyrifos Ki =4.46 µM; Phoxim, Ki = 3.27 µM). These results clearly suggest that AlepGOBP1 and AlepGOBP2 differentiate among odorants and other ligands. The molecular docking results further revealed different key residues involved in the ligand binding of AlepGOBPs. In summary, this study provides a foundation for exploring the olfactory mechanism of A. lepigone and identified two potential target genes for the development of highly effective insecticides in the future.


Assuntos
Inseticidas , Mariposas , Atrativos Sexuais , Animais , China , Escherichia coli , Proteínas de Insetos , Simulação de Acoplamento Molecular , Odorantes , Feromônios
14.
PLoS One ; 15(4): e0230123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267843

RESUMO

OBJECTS: To look into the discharge pharmacotherapy for type 2 diabetics admitted to two general hospitals of different ranks and inspect current real-world management of discharge pharmacology and its related factors. METHODS: Type 2 diabetics admitted to a tertiary general hospital (Ningbo Medical Treatment Centre Lihuili Hospital, LHLH) or a secondary general hospital (Simen Hospital, SMH) for intensification of their anti-diabetics were included for retrospective analysis. Patients' demographics, clinical characteristics, admission diabetes therapy and discharge diabetes pharmacology were analyzed and compared among patients in each hospital as well as between two hospitals. RESULTS: 391 patients from LHLH and 164 patients from SMH were included for analyzing. Compared with patients from LHLH, patients from SMH were older, more illiterate and had higher HbA1c concentrations. While there was a nearly equal split of oral anti-diabetes drugs (OADs)-only and Insulin treatment in LHLH's discharge pharmacotherapy, insulin treatment dominated SMH's. Basal-and-bolus insulin assumed the majority of SMH's insulin regimens but only accounted for less than 20% of LHLH's. The principal discrepancy in OADs-only treatment existed in the utilization of newer classes of OADs. Cost and body mass index (BMI) were the main differentiating factors among OADs-only treatments while duration, BMI and HbA1c differ among insulin treatments at LHLH. Clinical characteristics didn't significantly differ among OADs-only treatments and HbA1c was the only differentiating factor among insulin treatments at SMH. Overall, hospital, duration, HbA1c, and vascular diseases were main factors that affect discharge pharmacology. CONCLUSIONS: Great disparities exist in the discharge pharmacotherapy at two hospitals. Diabetes management is mostly glucose-oriented at SMH while multifactorial considerations were reflected in LHLH's discharge pharmacotherapy. Besides differences in patients' demographics, medication availability and diagnosis of early-stage vascular complications, lack of practical algorithm for discharge management in T2DM may be the underlying deficiency and a key part for future improvement.

15.
Brain Imaging Behav ; 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32304020

RESUMO

Patients with end-stage renal disease (ESRD) are notably accompanied by cognitive disorder and anxiety or depressive symptom. We aimed to explore the linkages of the amygdala-based MR parameters, cognitive and mood performance, systematic inflammation and gut microbiota in ESRD. This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 43.9 ± 13.8 years) and 19 age- and sex-matched healthy control (HC) (12 males and 7 females, mean age of 44.1 ± 10.0 years). All subjects underwent cognitive assessment, inflammatory factor and stool microbiota analysis, and brain MRI analysis [amygdala-based functional connectivity and voxel-based morphometry (VBM)]. ERSD was separated by different microbiota strains. All factors were compared between ESRD and HC, as well as between ESRD subgroups. Pearson correlation analysis and causal mediation analysis were conducted to further investigate the relationship among the factors derived from the gut microbiota, brain and systemic inflammation. ESRD displayed gut dysbiosis and increased systemic inflammation when compared to HC (all P < 0.05). Meanwhile, ESRD showed smaller VBM in amygdala, decreased functional connectivity in left amygdala - right inferior parietal lobe [P < 0.05, Gaussian Random Field (GRF) corrected] and worse cognitive or mood performance. Moreover, ESRD-B (Prevutella mainly), when compared to ESRD-A (Bacteroides mainly), displayed increased interleukin-6, self-rating anxiety scale and functional connectivity in left amygdala - bilateral anterior cingulate cortex / medial superior frontal cortex (P < 0.05, GRF corrected). Furthermore, the correlation network of ESRD showed that both gut dysbiosis and amygdala-based alteration were correlated with cognitive performance and systemic inflammation. Causal mediation analysis validated that the disrupted distribution of Roseburia indirectly regulated the amygdala-based functional connectivity through tumor necrosis factor-alpha. The gut dysbiosis induced by ESRD was closely related to pro-inflammatory cytokines, amygdala-based phenotype, and mood performance. The lower abundance in Roseburia indirectly modulated amygdala-based functional connectivity pattern by tumor necrosis factor-alpha, which might provide a new way in diagnosis and treatment in patients of ESRD with depressive/anxious mood.

16.
J Mol Cell Biol ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32242230

RESUMO

Adipocyte is the most predominant cell type in the tumor microenvironment of breast cancer and plays a pivotal role in cancer progression, yet the underlying mechanisms and functional mediators remain elusive. We isolated primary preadipocytes from mammary fat pads of human breast cancer patients and generated mature adipocytes and cancer-associated adipocytes (CAAs) in vitro. The CAAs exhibited significantly different gene expression profiles as assessed by transcriptome sequencing. One of the highly expressed genes in CAAs is granulocyte colony-stimulating factor (G-CSF). Recombinant human G-CSF treatment or stably expression of human G-CSF in triple-negative breast cancer (TNBC) cell lines enhanced EMT, migration, and invasion of cancer cells, by activating Stat3. Accordantly, targeting G-CSF/Stat3 signaling with G-CSF-neutralizing antibody, a chemical inhibitor, or siRNAs for Stat3 could abrogate CAAs- or G-CSF-induced migration and invasion of breast cancer cells. The pro-invasive genes MMP2 and MMP9 were identified as target genes of G-CSF in TNBC cells. Furthermore, in human breast cancer tissues, elevated G-CSF expression in adipocytes is well correlated with activated Stat3 signal in cancer cells. Together, our results suggest a novel strategy to intervene with invasive breast cancers by targeting CAAs-derived G-CSF.

17.
Acta Pharmacol Sin ; 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32300244

RESUMO

Tissue kallikrein has protective function against various types of injury. In this study, we investigated whether exogenous pancreatic kininogenase (PK) conferred renoprotection in a rat model of unilateral ureteral obstruction (UUO) and H2O2-treated HK-2 cells in vitro. SD rats were subjected to UUO surgery, then PK (7.2 U/g per day, ip) was administered for 7 or 14 days. After the treatment, rats were euthanized; the obstructed kidneys were harvested for further examination. We found that PK administration significantly attenuated interstitial inflammation and fibrosis, and downregulated the expression of proinflammatory (MCP-1, TLR-2, and OPN) and profibrotic (TGF-ß1 and CTGF) cytokines in obstructed kidney. UUO-induced oxidative stress, closely associated with excessive apoptotic cell death and autophagy via PI3K/AKT/FoxO1a signaling, which were abolished by PK administration. We further showed that PK administration increased the expression of bradykinin receptors 1 and 2 (B1R and B2R) mRNA and the production of NO and cAMP in kidney tissues. Coadministration with either B1R antagonist (des-Arg9-[Leu8]-bradykinin) or B2R antagonist (icatibant) abrogated the renoprotective effects of PK, and reduced the levels of NO and cAMP in obstructed kidney. In H2O2-treated HK-2 cells, addition of PK (6 pg/mL) significantly decreased ROS production, regulated the expression of oxidant and antioxidant enzymes, suppressed the expression of TGF-ß1 and MCP-1, and inhibited cell apoptosis. Our data demonstrate that PK treatment protects against the progression of renal fibrosis in obstructed kidneys.

18.
Clin Neurophysiol ; 131(6): 1323-1331, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32304846

RESUMO

OBJECTIVE: Language experience can develop long-term memory traces for speech units in the brain, to ensure efficient processing of speech sounds. However, prelingually deafened children lack sufficient auditory input before cochlear implantation. Whether the experience-dependent long-term memory traces exist in prelingually deafened children with cochlear implants (CIs) remains unclear. METHODS: We presented CI and normal hearing (NH) children with Mandarin Chinese spoken disyllables in an oddball paradigm and recorded event-related potentials. Each disyllable was defined as a meaningful word or a meaningless pseudoword by the tonal information in the second syllable. RESULTS: The amplitude of mismatch negativity (MMN) elicited by words was larger than that elicited by pseudowords in NH children. However, this enhancement of the MMN amplitude was not found in CI children. Behavioral results showed later recognition points for words and lower accuracies for speech comprehension in CI children than in NH children. Furthermore, increased theta power for words compared with pseudowords was only found in NH children. CONCLUSIONS: Our findings indicate a deficit of long-term memory traces for words in prelingually deafened children with cochlear implants. SIGNIFICANCE: Early speech input may be crucial to the formation of long-term memory traces for speech units.

19.
Fish Shellfish Immunol ; 102: 82-91, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32302771

RESUMO

Carbohydrate sulfotransferases 11 (chst11) is one of the enzymes that synthesize chondroitin sulfate (CS), which has extensive immune functions in vitro and plays a critical role in mediating the infection of host by pathogenic microorganisms. However, whether it has immune functions in crayfish is still poorly understood. In our previous study of transcriptome, chst11 was differentially expressed in susceptible individuals and resistant individuals of Procambarus clarkii after white spot syndrome virus (WSSV) injection. Thus, in this study, the sequence of chst11 was obtained from P. clarkii for the first time and analyzed, and the expression pattern of chst11 was investigated. Besides, the purified recombinant protein of chst11 effect in protection in WSSV infection was explored. The full length of chst11 was 1536 bp with an 831-bp open reading frame (ORF), which encoding 276 amino acids residues with a calculated molecular mass of 33.1 kDa. The chst11 contains a Sulfotransfer_2 domain, one N-glycosylation site and three O-glycosylation sites. Phylogenetic analysis results showed that chst11 had the highest similarity to Penaeus vannamei (79.93%). The expression pattern of chst11 in different tissues indicated that chst11 was expressed highest in gut, gill and hypodermis, lowest in testicular duct, periesophageal nerve and hemocytes. The chst11 had different expression patterns in different tissues when the crayfish was challenged by WSSV, Aeromonas hydrophila and CpG ODN. Recombinant chst11 protein significantly reduced the amount of WSSV copy number in hepatopancreas at 6 h and 12 h post injection compared to the control group injected with bovine serum albumin (BSA). It was found that chst11 protein enhanced the expression of peroxinectin, proPO in hepatopancreas and midgut and the C-type lectin (ctl) in hemocytes and hepatopancreas. Intramuscularly injection of juvenile crayfish with chst11 protein decreased 60% mortality compared to the control group with BSA. This study is the first report on the antiviral function of chst11 in the immune system of crustacean.

20.
Cell Death Dis ; 11(2): 155, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111819

RESUMO

Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest lncRNA of LDLRAD4, and its expression levels, cellular localization, precise function, and mechanism in colorectal cancer (CRC) remain unknown. In this study, we observed that lncRNA LDLRAD4-AS1 was located in the nucleus of CRC cells and that lncRNA LDLRAD4-AS1 was upregulated in most CRC specimens and cell lines. Overexpression of lncRNA LDLRAD4-AS1 was correlated with poor prognosis in CRC patients. LncRNA LDLRAD4-AS1 upregulation enhanced the migration and invasion of CRC cells in vitro and facilitated CRC metastasis in vivo. Mechanistic investigations suggested that lncRNA LDLRAD4-AS1 could decrease the expression of LDLRAD4 by disrupting the stability of LDLRAD4 mRNA, resulting in epithelial-to-mesenchymal transition (EMT) through upregulating Snail, thereby promoting metastasis in CRC. Our results demonstrated a previously unrecognized LDLRAD4-AS1-LDLRAD4-Snail regulatory axis involved in epigenetic and posttranscriptional regulation that contributes to CRC progression and metastasis.

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