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1.
Medicine (Baltimore) ; 100(18): e25639, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950941

RESUMO

BACKGROUND: Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China. OBJECTIVE: This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients. METHODS: Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis. RESULTS: A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; P = .0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. P = .51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (P < .01), and prothrombin time (PT) was significantly increased (P < .05). CONCLUSION: Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.

2.
Phytochem Anal ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949013

RESUMO

INTRODUCTION: With the wide application of Scutellaria barbata D. Don for hepatitis and mastitis, its quality control issues have also received increasing attention. Based on the multi-component and multi-target characteristics of traditional Chinese medicine, there is an urgent need to establish a quality evaluation system. OBJECTIVES: This study intends to integrate the "quality-activity-quantification" strategy and establish an activity-related quality control method to ensure the safety and effectiveness of S. barbata. MATERIAL AND METHODS: Ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) was used to characterize the chemical components of S. barbata, and network pharmacological analysis was carried out on the identified components. The index components were determined on the basis of comprehensive activity prediction results and content information. At the same time, the contents of 16 batches of S. barbata from different origins were determined. RESULTS: A total of 94 compounds were identified according to mass spectrometric data, 12 of which were isolated and structure-confirmed by nuclear magnetic resonance technology. Network pharmacological analysis was applied to predict their key targets and the major pathways mediating their anti-inflammatory effects. On the basis of comprehensive activity prediction and content information, five components were chosen as crucial quality indicators of S. barbata, including scutellarin, scutellarein, luteolin, apigenin, and hispidulin. CONCLUSION: In this study, 16 different S. barbata batches were compared, and five quality indicators were determined on the basis of qualitative and activity results. The present study provides useful information for evaluating the quality of S. barbata in different areas, and also provides a new basis for the development of quality evaluation methods.

3.
Int J Biol Macromol ; 183: 463-472, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33932417

RESUMO

Two alcohol soluble glutenins (ASGLUs) were extracted from gluten and further separated by column chromatography. The ASGLUs with Mw lower than 20,000 (ASGLU 1) and Mw higher than 70,000 (ASGLU 2) show the total amino acid contents of 86.71 g/100 g and 62.847 g/100 g respectively. Both of them are rich in Glu (45.574% and 43.224%) and Pro (15.447% and 16.370%) while poor in cys-s, met and lys (less than 1%). When wheat amylopectin/amylose retrogrades with those ASGLUs, the retrogradation rate of amylopectin with ASGLU 1 enhances significantly. UV-Vis, X-ray diffraction, FT-IR, DSC, CD and solid 13C NMR suggest that the double helixes of amylopectin short-chain branching are unwound during gelatinization. The hydrogen bonds of ASGLU 1 between amide and carbonyl oxygen are destroyed, meanwhile, ß-sheets are unfolded. During retrogradation, ASGLU 1 with less steric hindrance gets into the crevice of amylopectin and combines with the short-chain branching by hydrogen bond. The retrogradation dynamics show that the nucleation type of amylopectin-ASGLU 1 changes from instantaneous to rod-like growth during the process of retrogradation. ß-sheet of ASGLU 1 changes to ß-turn and random conformations at the meantime. The results provide a key targeting to control retrogradation of dough.

4.
Database (Oxford) ; 20212021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33942874

RESUMO

It is now known that cap-independent translation initiation facilitated by internal ribosome entry sites (IRESs) is vital in selective cellular protein synthesis under stress and different physiological conditions. However, three problems make it hard to understand transcriptome-wide cellular IRES-mediated translation initiation mechanisms: (i) complex interplay between IRESs and other translation initiation-related information, (ii) reliability issue of in silico cellular IRES investigation and (iii) labor-intensive in vivo IRES identification. In this research, we constructed the Human IRES Atlas database for a comprehensive understanding of cellular IRESs in humans. First, currently available and suitable IRES prediction tools (IRESfinder, PatSearch and IRESpy) were used to obtain transcriptome-wide human IRESs. Then, we collected eight genres of translation initiation-related features to help study the potential molecular mechanisms of each of the putative IRESs. Three functional tests (conservation, structural RNA-protein scores and conditional translation efficiency) were devised to evaluate the functionality of the identified putative IRESs. Moreover, an easy-to-use interface and an IRES-translation initiation interaction map for each gene transcript were implemented to help understand the interactions between IRESs and translation initiation-related features. Researchers can easily search/browse an IRES of interest using the web interface and deduce testable mechanism hypotheses of human IRES-driven translation initiation based on the integrated results. In summary, Human IRES Atlas integrates putative IRES elements and translation initiation-related experiments for better usage of these data and deduction of mechanism hypotheses. Database URL: http://cobishss0.im.nuk.edu.tw/Human_IRES_Atlas/.

5.
Sci China Life Sci ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33945069

RESUMO

Large tumor suppressor 1 (LATS1) is the key kinase controlling activation of Hippo signalling pathway. Post-translational modifications of LATS1 modulate its kinase activity. However, detailed mechanism underlying LATS1 stability and activation remains elusive. Here we report that LATS1 is acetylated by acetyltransferase CBP at K751 and is deacetylated by deacetylases SIRT3 and SIRT4. Acetylation at K751 stabilized LATS1 by decreasing LATS1 ubiquitination and inhibited LATS1 activation by reducing its phosphorylation. Mechanistically, LATS1 acetylation resulted in inhibition of YAP phosphorylation and degradation, leading to increased YAP nucleus translocation and promoted target gene expression. Functionally, LATS1-K751Q, the acetylation mimic mutant potentiated lung cancer cell migration, invasion and tumor growth, whereas LATS1-K751R, the acetylation deficient mutant inhibited these functions. Taken together, we demonstrated a previously unidentified post-translational modification of LATS1 that converts LATS1 from a tumor suppressor to a tumor promoter by suppression of Hippo signalling through acetylation of LATS1.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33858314

RESUMO

BACKGROUND: Dysregulation of microRNAs (miRNAs) figures prominently in radio-sensitivity of non-small cell lung cancer (NSCLC). MiR-129-5p can block the development of a variety of tumors. However, whether miR-129-5p modulates radio-sensitivity of NSCLC cells remains unknown. OBJECTIVE: This study was aimed to explore the role and the underlying mechanism of miR-129-5p in the radiosensitivity of NSCLC. METHODS: Radio-resistant NSCLC cell lines (A549-R and H1299-R) were constructed using A549 and H1299 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to quantify miR-129-5p, SRY-box transcription factor 4 (SOX4) mRNA, and RUNX family transcription factor 1 (RUNX1) mRNA expression levels. Cell apoptosis and cell cycle were detected by flow cytometry. Cell counting kit-8 (CCK-8) assay and colony formation experiments were used to measure cell proliferation. γ-H2AX was examined by Western blot to confirm DNA injury. Dual-luciferase reporter experiments were applied to analyze the interactions among miR-129-5p, RUNX1, and SOX4. RESULTS: In A549-R and H1299-R cells, compared with the wild type cell lines, miR-129-5p expression was remarkably reduced while SOX4 and RUNX1 expressions were increased. The transfection of miR-129-5p into NSCLC cell lines, markedly induced cell apoptosis, DNA injury, and cell cycle arrest, and inhibited cell proliferation and colony formation. RUNX1 and SOX4 were validated as target genes of miR-129-5p, and the restoration of RUNX1 or SOX4 could counteract the influence of miR-129-5p on A549-R cells. CONCLUSION: MiR-129-5p sensitizes A549-R and H1299-R cells to radiation by targeting RUNX1 and SOX4.

7.
Acta Pharmacol Sin ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859344

RESUMO

Hemorrhagic transformation (HT) is a common serious complication of stroke after thrombolysis treatment, which limits the clinical use of tissue plasminogen activator (t-PA). Since early diagnosis and treatment for HT is important to improve the prognosis of stroke patients, it is urgent to discover the potential biomarkers and therapeutic drugs. Recent evidence shows that pinocembrin, a natural flavonoid compound, exerts anti-cerebral ischemia effect and expands the time window of t-PA. In this study, we investigated the effect of pinocembrin on t-PA-induced HT and the potential biomarkers for HT after t-PA thrombolysis, thereby improving the prognosis of stroke. Electrocoagulation-induced thrombotic focal ischemic rats received intravenous infusion of t-PA (10 mg/kg) 6 h after ischemia. Administration of pinocembrin (10 mg/kg, iv) prior t-PA infusion significantly decreased the infarct volume, ameliorated t-PA-induced HT, and protected blood-brain barrier. Metabolomics analysis revealed that 5 differential metabolites in the cerebral cortex and 16 differential metabolites in serum involved in amino acid metabolism and energy metabolism were significantly changed after t-PA thrombolysis, whereas pinocembrin administration exerted significant intervention effects on these metabolites. Linear regression analysis showed that lactic acid was highly correlated to the occurrence of HT. Further experiments confirmed that t-PA treatment significantly increased the content of lactic acid and the activity of lactate dehydrogenase in the cerebral cortex and serum, and the expression of monocarboxylate transporter 1 (MCT 1) in the cerebral cortex; pinocembrin reversed these changes, which was consistent with the result of metabolomics. These results demonstrate that pinocembrin attenuates HT after t-PA thrombolysis, which may be associated with the regulation of endogenous metabolites. Lactic acid may be a potential biomarker for HT prediction and treatment.

8.
Commun Biol ; 4(1): 436, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790388

RESUMO

Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs. Fibrous coverings of nerves and blood vessels create structural continuity beyond organ boundaries. We recently validated fluid flow through human fibrous tissues, though whether these interstitial spaces are continuous through the body or discontinuous, confined within individual organs, remains unclear. Here we show evidence for continuity of interstitial spaces using two approaches. Non-biological particles (tattoo pigment, colloidal silver) were tracked within colon and skin interstitial spaces and into adjacent fascia. Hyaluronic acid, a macromolecular component of interstitial spaces, was also visualized. Both techniques demonstrate interstitial continuity within and between organs including within perineurium and vascular adventitia traversing organs and the spaces between them. We suggest that there is a body-wide network of fluid-filled interstitial spaces that has significant implications for molecular signaling, cell trafficking, and the spread of malignant and infectious disease.

9.
Cancer Control ; 28: 10732748211009245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33887987

RESUMO

Kynurenine 3-monooxygenase (KMO) is the pivotal enzyme in the kynurenine pathway and is located on the mitochondrial outer membrane. The dysregulation of KMO leads to various neurodegenerative diseases; however, it is rarely mentioned in cancer progression. Our previous study showed that KMO overexpression in canine mammary gland tumors (cMGT) is associated with poor prognosis in cMGT patients. Surprisingly, it was also found that KMO can be located on the cell membranes of cMGT cells, unlike its location in normal cells, where KMO is expressed only within the cytosol. Since cMGT and human breast cancer share similar morphologies and pathogenesis, this study investigated the possibility of detecting surface KMO in human breast cancers and the role of surface KMO in tumorigenesis. Using immunohistochemistry (IHC), flow cytometry (FC), immunofluorescence assay (IFA), and transmission electron microscopy (TEM), we demonstrated that KMO can be aberrantly and highly expressed on the cell membranes of breast cancer tissues and in an array of cell lines. Masking surface KMO with anti-KMO antibody reduced the cell viability and inhibited the migration and invasion of the triple-negative breast cancer cell line, MDA-MB-231. These results indicated that aberrant surface expression of KMO may be a potential therapeutic target for human breast cancers.

10.
SLAS Discov ; : 24725552211008854, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33870746

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the global COVID-19 pandemic. Nonstructural protein 14 (NSP14), which features exonuclease (ExoN) and guanine N7 methyltransferase activity, is a critical player in SARS-CoV-2 replication and fidelity and represents an attractive antiviral target. Initiating drug discovery efforts for nucleases such as NSP14 remains a challenge due to a lack of suitable high-throughput assay methodologies. This report describes the combination of self-assembled monolayers and matrix-assisted laser desorption ionization mass spectrometry to enable the first label-free and high-throughput assay for NSP14 ExoN activity. The assay was used to measure NSP14 activity and gain insight into substrate specificity and the reaction mechanism. Next, the assay was optimized for kinetically balanced conditions and miniaturized, while achieving a robust assay (Z factor > 0.8) and a significant assay window (signal-to-background ratio > 200). Screening 10,240 small molecules from a diverse library revealed candidate inhibitors, which were counterscreened for NSP14 selectivity and RNA intercalation. The assay methodology described here will enable, for the first time, a label-free and high-throughput assay for NSP14 ExoN activity to accelerate drug discovery efforts and, due to the assay flexibility, can be more broadly applicable for measuring other enzyme activities from other viruses or implicated in various pathologies.

11.
Plant Dis ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881917

RESUMO

Wheat powdery mildew is a devastating disease that seriously threatens yield worldwide. Utilization of host resistance is considered an effective strategy to minimize powdery mildew damage. Pm21, PmV, and Pm12 confer broad-spectrum resistance to wheat powdery mildew in China, of which Pm21 and PmV are allelic genes derived from the 6VS chromosome of Dasypyrum villosum, and Pm12 is derived from the 6SS chromosome of Aegilops speltoides and most likely orthologous to the former two genes. To accurately and efficiently transfer and pyramid these genes using marker-assisted selection (MAS), distinctive single nucleotide polymorphisms (SNPs) among the exon sequences of Pm21, PmV, and Pm12 and their homologous sequences in the common wheat genome were identified and used for developing diagnostic Kompetitive Allele-Specific PCR (KASP) markers. The markers were validated in different genotypes including transgenic vectors, transgenic lines, translocation lines, resistance stocks with documented Pm genes, and in multiple susceptible cultivars without Pm genes. As a result, we initially developed a KASP marker that can simultaneously diagnose Pm21, Pm12, and PmV. Subsequently, we obtained a highly diagnostic KASP marker for each of the three genes that could distinguish among the three genes and also accurately distinguish them from other resistant stocks with documented Pm genes and from multiple susceptible genotypes. Compared with previously reported markers, the highly diagnostic KASP markers developed in this study have the advantages of low cost, easy assay, accuracy, and potentially high throughput for MAS.

12.
Urol Int ; : 1-9, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882508

RESUMO

INTRODUCTIONS: The objective of this study was to determine the prognostic value of positive lymph nodes (LNs) in patients with renal cell carcinoma (RCC) and tumor thrombus (TT) and to explore risk factors predicting LNs metastasis. METHODS: We retrospectively analyzed 216 patients with RCC and TT treated at a single institution from January 2015 to December 2019. Overall survival (OS) and progression-free survival (PFS) was estimated using the Kaplan-Meier curves divided by pathological LN status. Associations between clinicopathological features and survival outcomes were evaluated using Cox regression models. Logistic regression model was performed to determine risk factors associated with LN metastasis. RESULTS: We identified 216 patients with RCC and TT including 85 (39.4%) who did and 131 (60.6%) who did not undergo lymph node dissection. Pathologically positive LNs were found in 18 (8.3%) cases. pN1 had significant worse OS (median: 21 vs. 41 and 56 months, p < 0.001) and PFS (median:14 vs. 29 and 33 months, p < 0.001) than pN0 and pNx respectively. However, survival outcomes of OS and PFS were similar between pNx-0/M1 and pN1/M0 group and between 1- and ≥2-node-positive group. Non-CCRCC (p = 0.001), sarcomatoid differentiation (p < 0.001), and pathologically positive LNs (p = 0.025) were independent prognostic predictors predicting worse OS while distance metastasis (p = 0.009), non-CCRCC (p = 0.023), necrosis (p = 0.014), sarcomatoid differentiation (p = 0.003), and pathologically positive LNs (p = 0.007) were independent prognostic indicators predicting worse PFS. Clinically positive LNs (p = 0.014) and sarcomatoid differentiation (p = 0.009) were predictors of positive LNs. CONCLUSIONS: LNs metastasis independently associated with worse survival outcomes in RCC and TT populations, with similar survival outcomes compared to distance metastasis. Therefore, more accurate risk stratification is warranted for guiding postoperative surveillance and adjuvant therapy.

13.
Chem Commun (Camb) ; 57(33): 3975-3978, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885681

RESUMO

A phosphorus allotrope called greenish phosphorus was successfully synthesized via a simple chemical vapor deposition method. We revealed that the critical factors in the formation mechanism of greenish phosphorus are the partial pressure of the phosphorus vapor and the structure of the substrate. On the substrates of a glassy carbon wafer and carbon paper, the edge carbon structure can activate P4 molecules, allowing them to polymerize due to strong adsorption (Ead = -1.62 eV). Greenish phosphorus possesses a distinct crystal structure, different from red phosphorus and black phosphorus, thus leading to unique physical and chemical properties, and potential applications in optical, electrical, and magnetic fields.

14.
Zhongguo Zhen Jiu ; 41(3): 263-7, 2021 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-33798307

RESUMO

OBJECTIVE: To observe the clinical effect of acupuncture at Tiaoshen (regulating the spirit) acupoints on chronic insomnia and hyperarousal state, and explore its possible mechanism. METHODS: A total of 60 patients with chronic insomnia were randomly divided into an acupuncture group (30 cases, 1 case dropped off) and a sham acupuncture group (30 cases, 1 cases dropped off). Both groups were given basic sleep health education. The acupuncture group was treated with acupuncture at Tiaoshen acupoints including Baihui (GV 20), Shenting (GV 24), Yintang (GV 29), Shenmen (HT 7) and Sanyinjiao (SP 6). The sham acupuncture group was treated with non-effective point shallow acupuncture. Both groups were treated once every other day, 3 times a week for 4 weeks. The Pittsburgh sleep quality index (PSQI) score, pre-sleep arousal scale (PSAS) score, hyperarousal scale (HAS) score, and serum gamma-aminobutyric acid (GABA) level before and after treatment were compared between the two groups. RESULTS: Compared before treatment, the sleep quality, time to fall asleep, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI, various scores and total score of PSAS, and HAS score in the acupuncture group after treatment were decreased (P<0.05, P<0.01); in the sham acupuncture group, the time to fall asleep, daytime dysfunction scores and total score of PSQI, and cognitive arousal score of PSAS after treatment were decreased (P<0.05). After treatment, the sleep quality, time to fall asleep, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI, various scores and total score of PSAS, and HAS score in the acupuncture group were lower than those in the sham acupuncture group (P<0.05, P<0.01). Compared before treatment, the serum GABA level in the acupuncture group were increased (P<0.05), and the serum GABA level in the acupuncture group was higher than that in the sham acupuncture group after treatment (P<0.05). CONCLUSION: Acupuncture at Tiaoshen acupoints can obviously improve the sleep and hyperarousal state of patients with chronic insomnia, and up-regulating serum GABA content is one of its possible mechanisms.


Assuntos
Terapia por Acupuntura , Distúrbios do Início e da Manutenção do Sono , Pontos de Acupuntura , Nível de Alerta , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
15.
Artigo em Chinês | MEDLINE | ID: mdl-33896152

RESUMO

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule(GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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16.
Cancer Biomark ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33896823

RESUMO

BACKGROUND: MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). OBJECTIVE: The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. METHODS: A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. RESULTS: The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. CONCLUSIONS: A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

17.
Biomedicines ; 9(3)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804115

RESUMO

Congenital nephrogenic diabetes insipidus (CNDI) is a genetic disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 genes, rendering collecting duct cells insensitive to the peptide hormone arginine vasopressin stimulation for water reabsorption. This study reports a first identified AVPR2 mutation in Taiwan and demonstrates our effort to understand the pathogenesis caused by applying computational structural analysis tools. The CNDI condition of an 8-month-old male patient was confirmed according to symptoms, family history, and DNA sequence analysis. The patient was identified to have a valine 279 deletion-mutation in the AVPR2 gene. Cellular experiments using mutant protein transfected cells revealed that mutated AVPR2 is expressed successfully in cells and localized on cell surfaces. We further analyzed the pathogenesis of the mutation at sub-molecular levels via long-term molecular dynamics (MD) simulations and structural analysis. The MD simulations showed while the structure of the extracellular ligand-binding domain remains unchanged, the mutation alters the direction of dynamic motion of AVPR2 transmembrane helix 6 toward the center of the G-protein binding site, obstructing the binding of G-protein, thus likely disabling downstream signaling. This study demonstrated that the computational approaches can be powerful tools for obtaining valuable information on the pathogenesis induced by mutations in G-protein-coupled receptors. These methods can also be helpful in providing clues on potential therapeutic strategies for CNDI.

18.
Toxins (Basel) ; 13(4)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921529

RESUMO

Our climate is projected to change gradually over time. Mycotoxin occurrence in cereal grains is both directly and indirectly related to local weather and to climate changes. Direct routes are via the effects of precipitation, relative humidity, and temperatures on both fungal infection of the grain and mycotoxin formation. Indirect routes are via the effects of the wind dispersal of spores, insect attacks, and shifts in cereal grain phenology. This review aimed to investigate available modeling studies for climate change impacts on mycotoxins in cereal grains, and to identify how they can be used to safeguard food safety with future climate change. Using a systematic review approach, in total, 53 relevant papers from the period of 2005-2020 were retrieved. Only six of them focused on quantitative modeling of climate change impacts on mycotoxins, all in pre-harvest cereal grains. Although regional differences exist, the model results generally show an increase in mycotoxins in a changing climate. The models do not give an indication on how to adapt to climate change impacts. If available models were linked with land use and crop models, scenario analyses could be used for analyzing adaptation strategies to avoid high mycotoxin presence in cereal grains and to safeguard the safety of our feed and food.

19.
Mol Med ; 27(1): 41, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858324

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) XIST has been implicated in the progression of a variety of tumor diseases. The purpose of this study was to explore the molecular role of lncRNA XIST in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: The expression levels of lncRNA XIST, miR-192 and TRIM25 in HBV-related HCC tissues and HepG2.2.15 cells were detected by qRT-PCR. Biological information and luciferin gene reporter assay were performed to detect the interaction among lncRNA XIST, miR-192 and TRIM25. CCk-8 assay, wound healing assay and colony formation assay were conducted to detect the proliferation and migration ability of HepG2.2.15 cells. RESULTS: qRT-PCR results showed that the expression levels of lncRNA XIST were remarkably increased in HBV-related HCC tissues and HepG2.2.15 cells. In addition, miR-192 was a direct target gene of lncRNA XIST, and the expression of miR-192 and lncRNA XIST were negatively correlated. Moreover, overexpression of miR-192 observably inhibited the proliferation and migration of HCC cells, while overexpression of lncRNA XIST showed an opposite effect. Furthermore, TRIM25 was a direct target of miR-192, and lncRNA XIST could up-regulate the expression of TRIM25 by targeting miR-192. CONCLUSION: LncRNA XIST could up-regulate the expression of TRIM25 by targeting and binding to miR-192, thus accelerating the occurrence and development of HCC.

20.
J Cardiothorac Surg ; 16(1): 98, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879206

RESUMO

BACKGROUND: Heart failure (HF) is one of the leading causes of mortality and morbidity. The PARACHUTE device is designed to partition for left ventricular (LV) apical aneurysm post extensive anterior myocardial infarction (MI). However, the long-term prognosis of the PARACHUTE device post-implantation is unclear. METHODS: From November 2015 to April 2017, six subjects with New York Heart Association Classes II, III and IV ischemic HF, LV ejection fraction between (LVEF) 15 and 40%; and LV anterior apical aneurysm were enrolled in our center. The cumulative event rates for MI, hospitalization, and mortality were documented. Further assessment of LVEF, LV end-diastolic diameter (LVEDD), and estimated pulmonary artery pressure were determined by echocardiography core laboratory. For quantitative data comparison, paired t-test was employed. RESULTS: Device implantation was successful in all six enrolled subjects, and acute device association adverse events were not observed. At 4.6 ± 1.7 years follow-up, major adverse cardiac events (MACEs) were found in 50% patients, and the survival rate was 86.7%. We observed that the LVEF was significantly elevated after deployment (46.00 ± 6.00% vs. 35.83 ± 1.47%, P = 0.009). Besides, the LVEDD elevated after MI (51.17 ± 3.71 vs. 62.83 ± 3.25, P < 0.001) was revealed, but the device sustained preserved LVEDD after implantation. CONCLUSION: The PARACHUTE device is an alternative therapy for patients with severe LV maladaptive remodeling. However, the device seems to increase the HF ratio. TRIAL REGISTRATION: NCT02240940.

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