Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.633
Filtrar
1.
Tour Manag ; 83: 104240, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33082615

RESUMO

Effective air-travel stress management is increasingly crucial in determining tourist satisfaction and travel choices, particularly in a time of intensive fear about virus, terrorism, and plane crashes. However, research about air-travel stress, particularly what and how various influential forces shape passenger stress levels, is still in its infancy. The current research proposes the adoption of Conservation of Resources (COR) theory as a holistic schema to identify through resource dynamics the potential influential forces for air-travel stress across leisure travel stages. The findings, based on surveying passengers at the gate of multi-country international and domestic airports, demonstrates the capability of COR schema to predict and explain the influences on air-travel stress from an array of personal and situational/trip-specific factors. The theoretical advances from COR-based cross-stage stress analyses, and the guidance for customized airline/airport stress-soothing service strategies are discussed.

2.
Int Urogynecol J ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206221

RESUMO

INTRODUCTION AND HYPOTHESIS: Personality traits can play an important role in outcomes of different chronic disorders. We hypothesize that the pessary treatment outcomes in symptomatic pelvic organ prolapse (POP) can also be influenced by personality traits. METHODS: This prospective observational study included consecutive women with symptomatic POP seeking pessary treatment between December 2018 and January 2020. The personality profile was measured using the Eysenck Personality Questionnaire (EPQ-R) at baseline, and patient health-related quality of life (HRQoL) was measured using the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) and the Pelvic Floor Distress Inventory (PFDI-20) at baseline and at 3 months. The correlation between HRQoL and personality traits was investigated by means of linear regression. RESULTS: In total, 213 patients were included, of which 163 patients (76.5%) achieved success by the 3-month follow-up. No significant differences were found in the EPQ scores between the successful and unsuccessful groups. The scores on both the PFIQ-7 and PFDI-20 correlated significantly with neuroticism and correlated inversely with extraversion at both baseline and the 3-month follow-up. The degree of improvement in PFIQ-7 and PFDI-20 scores was not associated with personality traits. CONCLUSIONS: Our data indicate that neurotic and introverted women were more bothered by POP-related symptoms, although the improvement in symptoms was not significantly associated with personality traits after 3 months of pessary treatment.

3.
BMC Genomics ; 21(1): 803, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208105

RESUMO

BACKGROUND: Eucalyptus, a highly diverse genus of the Myrtaceae family, is the most widely planted hardwood in the world due to its increasing importance for fiber and energy. Somatic embryogenesis (SE) is one large-scale method to provide commercial use of the vegetative propagation of Eucalyptus and dedifferentiation is a key step for plant cells to become meristematic. However, little is known about the molecular changes during the Eucalyptus SE. RESULTS: We compared the transcriptome profiles of the differentiated and dedifferentiated tissues of two Eucalyptus species - E. camaldulensis (high embryogenetic potential) and E. grandis x urophylla (low embryogenetic potential). Initially, we identified 18,777 to 20,240 genes in all samples. Compared to the differentiated tissues, we identified 9229 and 8989 differentially expressed genes (DEGs) in the dedifferentiated tissues of E. camaldulensis and E. grandis x urophylla, respectively, and 2687 up-regulated and 2581 down-regulated genes shared. Next, we identified 2003 up-regulated and 1958 down-regulated genes only in E. camaldulensis, including 6 somatic embryogenesis receptor kinase, 17 ethylene, 12 auxin, 83 ribosomal protein, 28 zinc finger protein, 10 heat shock protein, 9 histone, 122 cell wall related and 98 transcription factor genes. Genes from other families like ABA, arabinogalactan protein and late embryogenesis abundant protein were also found to be specifically dysregulated in the dedifferentiation process of E. camaldulensis. Further, we identified 48,447 variants (SNPs and small indels) specific to E. camaldulensis, including 13,434 exonic variants from 4723 genes (e.g., annexin, GN, ARF and AP2-like ethylene-responsive transcription factor). qRT-PCR was used to confirm the gene expression patterns in both E. camaldulensis and E. grandis x urophylla. CONCLUSIONS: This is the first time to study the somatic embryogenesis of Eucalyptus using transcriptome sequencing. It will improve our understanding of the molecular mechanisms of somatic embryogenesis and dedifferentiation in Eucalyptus. Our results provide a valuable resource for future studies in the field of Eucalyptus and will benefit the Eucalyptus breeding program.

4.
Nature ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33149299

RESUMO

Interferon-induced transmembrane protein 3 (IFITM3) has previously been identified as an endosomal protein that blocks viral infection1-3. Here we studied clinical cohorts of patients with B cell leukaemia and lymphoma, and identified IFITM3 as a strong predictor of poor outcome. In normal resting B cells, IFITM3 was minimally expressed and mainly localized in endosomes. However, engagement of the B cell receptor (BCR) induced both expression of IFITM3 and phosphorylation of this protein at Tyr20, which resulted in the accumulation of IFITM3 at the cell surface. In B cell leukaemia, oncogenic kinases phosphorylate IFITM3 at Tyr20, which causes constitutive localization of this protein at the plasma membrane. In a mouse model, Ifitm3-/- naive B cells developed in normal numbers; however, the formation of germinal centres and the production of antigen-specific antibodies were compromised. Oncogenes that induce the development of leukaemia and lymphoma did not transform Ifitm3-/- B cells. Conversely, the phosphomimetic IFITM3(Y20E) mutant induced oncogenic PI3K signalling and initiated the transformation of premalignant B cells. Mechanistic experiments revealed that IFITM3 functions as a PIP3 scaffold and central amplifier of PI3K signalling. The amplification of PI3K signals depends on IFITM3 using two lysine residues (Lys83 and Lys104) in its conserved intracellular loop as a scaffold for the accumulation of PIP3. In Ifitm3-/- B cells, lipid rafts were depleted of PIP3, which resulted in the defective expression of over 60 lipid-raft-associated surface receptors, and impaired BCR signalling and cellular adhesion. We conclude that the phosphorylation of IFITM3 that occurs after B cells encounter antigen induces a dynamic switch from antiviral effector functions in endosomes to a PI3K amplification loop at the cell surface. IFITM3-dependent amplification of PI3K signalling, which in part acts downstream of the BCR, is critical for the rapid expansion of B cells with high affinity to antigen. In addition, multiple oncogenes depend on IFITM3 to assemble PIP3-dependent signalling complexes and amplify PI3K signalling for malignant transformation.

5.
Lab Chip ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155006

RESUMO

Noninvasive detection of circulating fetal cells carrying the entire fetal genome is a promising way for prenatal testing of genetic diseases. However, ideal approaches for efficient separation of these valuable cells are not available. Here, a novel inertial microfluidic chip (CelutriateChip 1) is developed for ultra-fast, label-free enrichment of circulating trophoblasts (CTBs) from the whole blood samples of pregnant women. The unique structural design of the four-stage curved channel in CelutriateChip 1 enables CTBs with larger size to be efficiently separated from the blood samples under the effect of inertial and Dean drag forces. The transition of the target cells among the stages enables CelutriateChip 1 to achieve one or two orders of magnitude higher throughput compared to single channel inertial microfluidic chips. After optimization of conditions, CTBs can be recovered from 2 mL of whole blood within 5 min with an average recovery efficiency ranging from 52.3% to 65.8% and high white blood cell depletion (99.95%). CTBs collected from the chip can be isolated at the single-cell level and used for downstream immunofluorescence staining and genetic genotyping. Clinical tests are performed on 30 pregnant women and the results demonstrate that CTBs are obtainable in 86.67% of pregnancy cases. A single-base variant in the HBB gene can be accurately detected by sequencing of rare CTBs. This simple, antibody-free and low-cost approach holds promise for obtaining rare CTBs for prenatal detection of various genetic diseases.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33174318

RESUMO

AIM: To evaluate the clinical efficacy and safety of laparoscopic adenomyomectomy combined with intraoperative replacement of levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of symptomatic adenomyosis. METHODS: This is a case-series study in a university medical center. A total of 52 patients with symptomatic adenomyosis were treated by laparoscopic adenomyomectomy combined with intraoperative replacement of LNG-IUS from January 2015 to July 2018. Visual analog scale, menstrual flow and uterine volume were compared before and after the surgery (3, 12 and 24 months). Meanwhile, LNG-IUS-induced adverse reactions (e.g. irregular vaginal bleeding, amenorrhea, expulsion, and perforation) were also recorded. RESULTS: All operations were successfully completed via laparoscopy without conversion to laparotomy. No severe complications were noted during the surgical procedure or follow-up period. The mean postoperative visual analog scale and menstrual flow scores and the volume of the uterus were significantly decreased (all P < 0.001) at 3, 12, and 24 months postoperatively, compared with preoperative scores. The clinical effective rates among the patients with dysmenorrhea were 98%, 96% and 96% at 3, 12 and 24 months after the operation, respectively. And the clinical effectiveness rate of menorrhagia was 97.6%, 95.2% and 95.2% at 3, 12 and 24 months after treatment, respectively. Among all related adverse reactions, amenorrhea was the most common (n = 12, 23.1%). There was one case of LNG-IUS perforation (1.9%) and two cases of expulsion (3.8%). CONCLUSION: Laparoscopic adenomyomectomy combined with intraoperative replacement of LNG-IUS is a novel and effective conservative surgical procedure for symptomatic adenomyosis treatment.

7.
Cell Biol Int ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33169892

RESUMO

Dental pulp stem cells (DPSCs) are capable of both self-renewal and multi-lineage differentiation, which play a positive role in dentinogenesis. Studies have shown that tumor necrosis factor-α (TNF-α) is involved in the differentiation of DPSCs under pro-inflammatory stimuli, but the mechanism of action of TNF-α is unknown. Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK) is a biomarker of early inflammatory response that plays a key role in modulating cell differentiation, but the role of RICK in DPSCs is still unclear. In this study, we identified that RICK regulates TNF-α-mediated odontogenic differentiation of DPSCs via the ERK signaling pathway. The expression of the biomarkers of odontogenic differentiation dental matrix protein-1 (DMP-1), dentin sialophosphoprotein (DSPP), biomarkers of odontogenic differentiation, increased in low concentration (1 ng/mL ~ 10 ng/mL) of TNF-α, and decreased in high concentration (50 ng/mL ~ 100 ng/mL). Odontogenic differentiation increased over time in odontogenic differentiation medium (ODI). In the presence of 10 ng/L TNF-α, the expression of RICK increased gradually over time along with odontogenic differentiation. Genetic silencing of RICK expression reduced the expression of odontogenic markers DMP-1 and DSPP. The ERK, but not the NF-κB signaling pathway was activated during the odontogenic differentiation of DPSCs. ERK signaling modulators decreased when RICK expression was inhibited. PD98059, an ERK inhibitor, blocked the odontogenic differentiation of DPSCs induced by TNF-α. These results provide a further theoretical and experimental basis for the potential use of RICK in targeted therapy for dentin regeneration. This article is protected by copyright. All rights reserved.

8.
J Psycholinguist Res ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044740

RESUMO

It hasn't been clear how holistic and analytic processing contribute to character recognition yet. The current study focused on two issues: (1) whether configural processing is sufficient to support the performance of identifying characters in absence of analytic processing; (2) whether configural processing involves multiple levels of character recognition. We examined the inversion effect in different levels of character processing from foveal to peripheral vision. Participants were asked to identify the stimulus from nine alternatives after a stimulus (character, radical, and stroke) is presented either in upright or inverted orientation. The results showed that the identification of characters and radicals had robust peripheral inversion effects at the locations of 6.2° and 12.2°, but the identification accuracies of inverted stimulus (parts only) remained above chance. These findings suggested that the configural processing of characters could not be isolated from analytical processing in the periphery in the current study. Furthermore, the greater inversion effect shown for characters than radicals at 6.2° might indicate that holistic processing of characters involves two levels of configurations: character structure and radical processing. The peripheral inversion effect for stroke was also observed and the role of stroke-based analytic in character recognition was discussed.

9.
BMC Surg ; 20(1): 226, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028289

RESUMO

BACKGROUND: The incidence of fractures around the femoral prosthesis among patients undergoing hip arthroplasty is increasing and has become the third leading cause of hip revision. While numerous methods for the surgical treatment of periprosthetic femoral fractures (PFFs) have been proposed, only few reports have examined the long-term efficacy of surgical treatment. This study aims to examine the mid-and long-term efficacy of surgical treatment among patients with Vancouver B2 and B3 PFFs. METHODS: This retrospective study evaluated the surgical outcomes of patients with Vancouver B2 and B3 PFFs between 2007 and 2011. The minimum follow-up time was eight years. Fracture healing, prosthesis stability, complications, patient quality of life SF-36 score, and survival rate were evaluated during the follow-up assessments. RESULTS: A total of 83 patients were included and had an average follow-up period of 120.3 months. Among these patients, 69 were classified as Vancouver B2 and were treated with a distal fixation stem, whereas 14 cases were classified as Vancouver B3 and were treated with modular femoral prosthesis by using a proximal femoral allograft technique. A total of 15 patients underwent secondary revision surgery, and prosthesis dislocation was identified as the main cause of secondary revision. 80 (96.4%) cases of fractures were clinically healed. The mortality rate in the first year after surgery was 8.4% (7/83). The overall 5-year Kaplan-Meier survival rate for these patients was 75.9%. Meanwhile, the 5-year Kaplan-Meier survival rate for the implants was 86.9%. The final follow-up SF-36 score of the patients was 48.3 ± 9.8. CONCLUSIONS: Patients with Vancouver B2 and B3 PFFs show high mortality in the first year after their surgery, and the Kaplan-Meier analysis results showed that such mortality tends to plateau after 5 years. Prosthesis dislocation was identified as the primary cause of secondary revision.

10.
JMIR Res Protoc ; 9(10): e21093, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33090114

RESUMO

BACKGROUND: Cervical cancer is the fourth most common cancer affecting women worldwide. In the 1980s, it was found that the sexually transmitted disease human papillomavirus causes over 90% of all cervical cancer cases. Since that discovery, diagnostic technologies have been developed for the detection of human papillomavirus DNA in cervical samples. However, significant sociocultural and structural barriers remain. Considerable strides have taken place in recent years to address these barriers, such as the self-collection for human papillomavirus-based cervical screening method. OBJECTIVE: The purpose of this review is to synthesize qualitative evidence around the self-collection method and identify strategies to increase acceptability and feasibility in different settings. This qualitative synthesis will be used to better understand how to conceptualize and implement more effective, accessible, and socially and culturally acceptable cervical screening programs and policies globally. METHODS: A systematic search will be conducted in Global Health, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ProQuest, ScienceDirect, EMBASE, EMCARE, Medline (OVID), Scopus, and Web of Science. Published and peer-reviewed articles will be included. Two reviewers will independently screen and assess the studies. The data will be coded and analyzed using a thematic synthesis process. The socioecological model will be used to organize emergent themes at the micro and macro levels. The results will be presented in narrative and tabular form. RESULTS: The article search and data extraction were completed in May 2020. The data were analyzed in June 2020. The review will be submitted for publication in Fall 2020. CONCLUSIONS: This review will present the global evidence of the perspectives and experiences of various key stakeholders and how these perspectives and experiences impact their decision-making process to perform or accept self-collection for human papillomavirus-based cervical screening. The review will provide guidance to implementation researchers as well as implications for future research. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42019109073; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=109073. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21093.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33082050

RESUMO

OBJECTIVE: To evaluate the necessity of postoperative repetitive uroflowmetry and postvoid residual volume (PVR) in women with advanced anterior vaginal prolapse. METHOD: Women with anterior vaginal prolapse stages III and IV who underwent surgery were included in this prospective cohort study. The surgical procedures included laparoscopic sacrocolpopexy (LSC), transvaginal mesh repair (TVM) and native tissue repair (NTR). Uroflowmetry, a PVR examination, the Urinary Distress Inventory-6 (UDI-6) and the Urinary Impact Questionnaire-7 (UIQ-7) were administered pre- and postoperatively. Moreover, pre- and postoperative uroflowmetry parameters were compared in women with/without an improvement in voiding difficulties according to the answer of questionnaires at one year after surgery. Paired sample t-tests, Wilcoxon signed-rank test, χ2 tests were used for analyses. RESULTS: A total of 85 women were included in the study, and data were available for 47 of them at 1-year follow-up. Approximately half of women with advanced anterior vaginal prolapse had symptoms of voiding dysfunction, the rate of which decreased to approximately 10% postoperatively. The UDI-6 and UIQ-7 indicated a significant improvement postoperatively from baseline (both p<0.05). The PVR decreased significantly after surgery (p = 0.000). Uroflowmetry parameters remained stable within 1 year after surgery (all p>0.05) both in the improved and unimproved groups (both p>0.05). CONCLUSION: Symptoms of voiding dysfunction are improved significantly after surgery. Postoperative uroflowmetry appears to be unnecessary one year after pelvic floor reconstructive surgery.

12.
PLoS One ; 15(10): e0240920, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33079966

RESUMO

As one of the most extensively studied glycosaminoglycan lyases, heparinase I has been used in producing low or ultra-low molecular weight heparin. Its' important applications are to neutralize the heparin in human blood and analyze heparin structure in the clinic. However, the low productivity and activity of the enzyme have greatly hindered its applications. In this study, a novel Hep-I from Bacteroides cellulosilyticus (BcHep-I) was successfully cloned and heterologously expressed in E. coli BL21 (DE3) as a soluble protein. The molecular mass and isoelectric point (pI) of the enzyme are 44.42 kDa and 9.02, respectively. And the characterization of BcHep-I after purified with Ni-NTA affinity chromatography suggested that it is a mesophilic enzyme. BcHep-I can be activated by 1 mM Ca2+, Mg2+, and Mn2+, while severely inhibited by Zn2+, Co2+, and EDTA. The specific activity of the enzyme was 738.3 U·mg-1 which is the highest activity ever reported. The Km and Vmax were calculated as 0.17 mg·mL-1 and 740.58 U·mg-1, respectively. Besides, the half-life of 300 min at 30°C showed BcHep-I has practical applications. Homology modeling and substrate docking revealed that Gln15, Lys74, Arg76, Lys104, Arg149, Gln208, Tyr336, Tyr342, and Lys338 were mainly involved in the substrate binding of Hep-I, and 11 hydrogen bonds were formed between heparin and the enzyme. These results indicated that BcHep-I with high activity has great potential applications in the industrial production of heparin, especially in the clinic to neutralize heparin.

13.
BMC Anesthesiol ; 20(1): 267, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092527

RESUMO

BACKGROUND: The catheter-related bladder discomfort (CRBD) of male patients is a common clinical problem, albeit lacking effective solutions. The present study aimed to investigate whether intravesical dexmedetomidine instillation alleviates the postoperative urinary discomfort in male patients with catheter under general anesthesia. METHODS: This single-blinded, prospective, randomized study included a total of 167 male patients American Society of Anesthesiologists (ASA) physical status I-II scheduled for surgery under general anesthesia were allocated to two groups: 84 in the dexmedetomidine group and 83 in the control group. Dexmedetomidine group patients received intravesical instillation of the drug 0.5 µg/kg and normal saline 20 mL, while the control group received intravesical instillation of 20 mL normal saline. The catheter was clamped for 30 min after intravesical instillation for all patients. CRBD scores and urethra pain numerical rating scale (NRS) scores were measured at admittance to post-anesthesia care unit (PACU) (T0), intravesical instillation (T1), 30 min (T2), 60 min (T3), 2 h (T4) after intravesical instillation, discharged from PACU (T5), and 6 h (T6) and 24 h (T7) after the operation. Patient satisfaction at discharge from PACU and 24 h post-operation were compared between the two groups. RESULTS: CRBD scores and urethra pain NRS scores after 30 min of intravesical dexmedetomidine instillation to 24 h post-operation were significantly lower than the control group (p < 0.001), and patient satisfaction was higher at discharge from PACU and 24 h post-operation (p < 0.001). No differences were detected in Steward score out of PACU (p = 0.213) and from the time of the end of operation to fully awake (p = 0.417). CONCLUSION: Intravesical dexmedetomidine instillation reduces postoperative urinary discomfort and urethra pain and improves satisfaction in male patients under general anesthesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR1800016429 ), date of registration 1st June 2018.

14.
Eur J Med Chem ; : 112951, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33109400

RESUMO

Four series of new 3-nitro naphthalimides derivatives, 4(4a‒4f), 5(5a‒5i), 6(6a‒6e) and 7 (7a‒7j), were designed and synthesized as antitumor agents. Methyl thiazolyl tetrazolium (MTT) screening assay results revealed that some compounds displayed effective in vitro antiproliferative activity on SMMC-7721, T24, SKOV-3, A549 and MGC-803 cancer cell lines in comparison with 5-fluorouracil (5-FU), mitonafide and amonafide. Nude mouse xenotransplantation model assay results indicated that compounds 6b and 7b exhibited good in vivo antiproliferative activity in MGC-803 xenografts in comparison with amonafide and cisplatin, suggesting that compounds 6b and 7b could be good candidates for antitumor agents. Gel electrophoresis assay indicated that DNA and Topo I were the potential targets of compounds 6b and 7b, and comet assay confirmed that compounds 6b and 7b could induce DNA damage, while the further study showed that the 6b- and 7b-induced DNA damage was accompanied by the upregulation of p-ATM, P-Chk2, Cdc25A and p-H2AX. Cell cycle arrest studies demonstrated that compounds 6b and 7b arrested the cell cycle at the S phase, accompanied by the upregulation of the expression levels of the antioncogene p21 and the down-regulation of the expression levels of cyclin E. Apoptosis assays indicated that compounds 6b and 7b caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-3, caspase-9 and PARP and the downregulation of Bcl-2. These mechanistic studies suggested that compounds 6b and 7b exerted their antitumor activity by targeting to DNA, thereby inducing DNA damage and Topo I inhibition, and consequently causing S stage arrest and the induction of apoptosis.

15.
Laryngoscope ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016340

RESUMO

OBJECTIVES/HYPOTHESIS: The individualized risk of airway obstruction after head and neck cancer surgery is unclear, especially oral and oropharyngeal cancer. The study aimed to establish an individualized predictive model for the necessity of temporary tracheotomy in these patients. METHODS: Patients who underwent oral and oropharyngeal cancer surgery from 1999 to 2019 were retrospectively reviewed. A nomogram was developed and validated in patients treated from 1999 to 2009 and 2010 to 2019, respectively. RESULTS: In total, 1551 patients were included. Oropharyngeal cancer, large tumor, midline crossing, preoperative radiation, mandibulectomy, flap reconstruction, and neck dissection were independent risk factors of postoperative airway obstruction in the training group (n = 707). A nomogram incorporating these factors had a C-index of 0.931 and was validated in the testing group (n = 844) (C-index, 0.918). Good calibration curves were observed in both groups. CONCLUSIONS: The nomogram successfully predicted the individual risk of postoperative airway obstruction for patients with oral and oropharyngeal cancer. LEVEL OF EVIDENCE: 4. Laryngoscope, 2020.

16.
Mol Cell Biochem ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33070275

RESUMO

Parkinson's disease (PD) is a disorder characterized by a progressive loss of the dopaminergic neurons in the substantia nigra and a depletion of the neurotransmitter dopamine in the striatum. Our published results indicate that fasciculation and elongation protein zeta-1 (FEZ1) plays a role in the astrocyte-mediated protection of dopamine neurons and regulation of the neuronal microenvironment during the progression of PD. In this study, we examined the effects of engrafted type-2 astrocytes (T2As) with high expression of FEZ1 on the improvement of the symptoms and functional reconstruction of PD rats. T2As were stereotactically transplanted into the striatum of rats with PD induced by 6-hydroxydopamine (6-OHDA). An examination of apomorphine (APO)-induced rotations was performed to evaluate dopamine neuron damage and motor functions. Remarkably, the grafted cells survived in the lesion environment for six weeks or longer after implantation. In addition, the transplantation of T2As decrease the average velocity and the duration time of the APO-induced rotations, and increase the actuation time, as measured in the rotation behavioural tests. In the substantia nigra, the transplantation of T2As reduced the PD-induced GFAP, TH and FEZ1 downregulation. The grafted cells exclusively migrated to other regions near the injection site in the striatum and differentiated into GFAP+ astrocytes or TH+ neurons. Furthermore, by detecting monoamine neurotransmitters through high-performance liquid chromatography, we found that the nigrostriatal pathway had been repaired to some extent. Taken together, these results suggest that engrafted T2As with high expression of FEZ1 improved the symptoms and functional reconstruction of PD rats, providing a theoretical basis for FEZ1 as a potential target and engraftment of T2As as a therapeutic strategy in the treatment of PD.

17.
Cell Metab ; 32(5): 726-735.e5, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33035493

RESUMO

Alterations in muscle mitochondrial substrate preference have been postulated to play a major role in the pathogenesis of muscle insulin resistance. In order to examine this hypothesis, we assessed the ratio of mitochondrial pyruvate oxidation (VPDH) to rates of mitochondrial citrate synthase flux (VCS) in muscle. Contrary to this hypothesis, we found that high-fat-diet (HFD)-fed insulin-resistant rats did not manifest altered muscle substrate preference (VPDH/VCS) in soleus or quadriceps muscles in the fasting state. Furthermore, hyperinsulinemic-euglycemic (HE) clamps increased VPDH/VCS in both muscles in normal and insulin-resistant rats. We then examined the muscle VPDH/VCS flux in insulin-sensitive and insulin-resistant humans and found similar relative rates of VPDH/VCS, following an overnight fast (∼20%), and similar increases in VPDH/VCS fluxes during a HE clamp. Altogether, these findings demonstrate that alterations in mitochondrial substrate preference are not an essential step in the pathogenesis of muscle insulin resistance.

18.
J Glob Health ; 10(2): 020510, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33110593

RESUMO

Background: As an emergent and fulminant infectious disease, Corona Virus Disease 2019 (COVID-19) has caused a worldwide pandemic. The early identification and timely treatment of severe patients are crucial to reducing the mortality of COVID-19. This study aimed to investigate the clinical characteristics and early predictors for severe COVID-19, and to establish a prediction model for the identification and triage of severe patients. Methods: All confirmed patients with COVID-19 admitted by the Second Affiliated Hospital of Air Force Medical University were enrolled in this retrospective non-interventional study. The patients were divided into a mild group and a severe group, and the clinical data were compared between the two groups. Univariate and multivariate analysis were used to identify the independent early predictors for severe COVID-19, and the prediction model was constructed by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the prediction model and each early predictor. Results: A total of 40 patients were enrolled in this study, of whom 19 were mild and 21 were severe. The proportions of patients with venerable age (≥60 years old), comorbidities, and hypertension in severe patients were higher than that of the mild (P < 0.05). The duration of fever and respiratory symptoms, and the interval from illness onset to viral clearance were longer in severe patients (P < 0.05). Most patients received at least one form of oxygen treatments, while severe patients required more mechanical ventilation (P < 0.05). Univariate and multivariate analysis showed that venerable age, hypertension, lymphopenia, hypoalbuminemia and elevated neutrophil lymphocyte ratio (NLR) were the independent high-risk factors for severe COVID-19. ROC curves demonstrated significant predictive value of age, lymphocyte count, albumin and NLR for severe COVID-19. The sensitivity and specificity of the newly constructed prediction model for predicting severe COVID-19 was 90.5% and 84.2%, respectively, and whose positive predictive value, negative predictive value and crude agreement were all over 85%. Conclusions: The severe COVID-19 risk model might help clinicians quickly identify severe patients at an early stage and timely take optimal therapeutic schedule for them.


Assuntos
Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Medição de Risco/estatística & dados numéricos , Índice de Gravidade de Doença , Adulto , Betacoronavirus , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos
19.
J BUON ; 25(4): 1714-1720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33099905

RESUMO

PURPOSE: The refractory nature and proneness to recurrence of lung cancer are related to the proliferation and differentiation of lung cancer stem cells (LCSCs). This paper aims to explore the effect of aquaporin-3 (AQP3) on the functions of LCSCs, and its molecular mechanism in regulating the differentiation and apoptosis of LCSCs through the Wnt/glycogen synthase kinase-3ß (GSK-3ß)/ß-catenin pathway. METHODS: The stem cells were selected and the cell lines with low expression of AQP3 were constructed, followed by transcriptome sequencing. LCSCs were transfected with empty lentivirus in the control group and transfected with AQP3 shRNA in the interference group, and the low expression of AQP3 was inhibited using the Wnt pathway inhibitor XAV939 in the interference+inhibitor group. The expressions of AQP3, Wnt/GSK-3ß/ß-catenin pathway genes, stemness genes, differentiation-related markers and apoptosis proteins in LCSCs were detected. RESULTS: In the interference group, the pathway genes were highly expressed. The genes in the interference group were enriched in the Wnt/GSK-3ß/ß-catenin pathway. In the interference group, the expressions of ß-catenin, GSK-3ß and signal transducer and activator of transcription 3 (STAT3) were significantly higher, while the expression of adenomatous polyposis coli (APC) was significantly lower (p<0.05). The expression of Wnt5α had no difference. In the interference group, the expressions of stemness-related genes were obviously higher, while the expression of CDK2 had no difference (p=0.471). The interference group had higher expressions of differentiation markers. CONCLUSION: AQP3 can reduce the differentiation and inhibit the apoptosis of LCSCs through reducing the expressions of Wnt/GSK-3ß/ß-catenin pathway-related genes such as ß-catenin, GSK-3ß and STAT3, thereby affecting the tumor progression.

20.
Acta Pharmacol Sin ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116249

RESUMO

To discover effective drugs for COVID-19 treatment amongst already clinically approved drugs, we developed a high throughput screening assay for SARS-CoV-2 virus entry inhibitors using SARS2-S pseudotyped virus. An approved drug library of 1800 small molecular drugs was screened for SARS2 entry inhibitors and 15 active drugs were identified as specific SARS2-S pseudovirus entry inhibitors. Antiviral tests using native SARS-CoV-2 virus in Vero E6 cells confirmed that 7 of these drugs (clemastine, amiodarone, trimeprazine, bosutinib, toremifene, flupenthixol, and azelastine) significantly inhibited SARS2 replication, reducing supernatant viral RNA load with a promising level of activity. Three of the drugs were classified as histamine receptor antagonists with clemastine showing the strongest anti-SARS2 activity (EC50 = 0.95 ± 0.83 µM). Our work suggests that these 7 drugs could enter into further in vivo studies and clinical investigations for COVID-19 treatment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA