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1.
Cells ; 10(3)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802813

RESUMO

Spermatogenesis is a complex and dynamic process which is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulating the normal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubular myoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility.

2.
J Proteomics ; : 104218, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831599

RESUMO

Selenium (Se) is an essential mineral nutrient for animals. Se deprivation can lead to many disorders and even death. This study investigated the response of Przewalski's gazelle (P. przewalskii) to Se-deprived environment. We found that Se deprivation in soil and forage not only influenced the mineral contents of the blood and hair in P. przewalskii, but also severely disrupted their blood parameters. We identified significant changes in the abundance of 146 proteins and 25 metabolites (P < 0.05) in serum, including the selenoproteins L8IG93 (glutathione peroxidase) and F4YD09 (Cu/Zn superoxide dismutase). Furthermore, the major known proteins and metabolites associated with the Se stress response in P. przewalskii were Cu/Zn superoxide dismutase, the vitamin K-dependent protein C, the C4b-binding protein alpha chain, complement component C7, lipase linoleic acid, peptidase D, thymidine, pseudo-uridine, L-phenylalanine, L-glutamine, PGA1, and 15-deoxy-delta-12,14-PGJ2. The main signaling pathways involved included complement and coagulation cascades, metabolic pathways, and stress granule formation. Our results indicate that the intake of Se-deficient forage elicited an oxidative stress response in P. przewalskii. These findings provide insights into the response mechanisms of this threatened gazelle to Se stress, and enable the development of conservation strategies to protect populations on the Qinghai-Tibetan Plateau. SIGNIFICANCE: This study is the first to point out the presence of oxidative stress in P. przewalskii in selenium-deficient areas through proteomics and metabolomics studies. These findings should prove helpful for conservation efforts aimed at P. przewalskii populations and maintenance of the integrity of their ecological environment.

3.
Ann Palliat Med ; 10(3): 3307-3312, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33849115

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was broken out in December 2019 and soon became a global health emergency. Effective treatment for COVID-19 is urgently needed. In the present study, we aimed to evaluate the antiviral effect of Arbidol vs. Chloroquine in treating COVID-19. METHODS: We retrospectively analyzed 62 patients with COVID-19 diagnosed according to the guidelines for diagnosis and treatment of COVID-19 in China. They were divided into two groups depending on the antiviral drugs that they received. Participants in the Arbidol group (n=42) received 0.2 g Arbidol, tid for 10 days,and those in Chloroquine group (n=20) received 500 mg Chloroquine, bid for 10 days. The coronavirus negative conversion time and the length of hospital stay were analyzed and compared between the two groups. RESULTS: There was no significant difference in demographic and clinical characteristics between the two groups. After antiviral treatment, the nasopharyngeal specimen negative conversion time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the length of hospital stay in the Arbidol group were significantly shorter than those in the Chloroquine group (18.50 vs. 25.05 days, P=0.001; 23.52 vs. 28.75 days, P=0.001). Adverse events observed during the antiviral treatment period were comparable between the two groups. Overall, 3 (7.14%) participants in the Arbidol group and 4 (20.0%) in the Chloroquine group experienced adverse events during antiviral treatment. CONCLUSIONS: These results suggest that Arbidol is advantageous over Chloroquine in terms of the SARS-CoV-2 negative conversion and the length of hospital stay in treating COVID-19 patients.

4.
Biol Trace Elem Res ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33851331

RESUMO

To assess the impacts of sulfur (S) and molybdenum (Mo) fertilization on antioxidant capacity of grazing Nanjiang brown goat in copper (Cu)-polluted meadow, and explore the control methods of Cu pollution in natural pasture, fertilizer treatments and grazing experiments were carried out in Garzê Tibetan Autonomous Prefecture of the Western Sichuan Plateau, Sichuan Province, Southwest China. 24 hm2 Cu-polluted meadows were fenced and randomly divided into four groups (3 replications/group, 2 hm2/replication): (1) control group, no fertilizer; (2) treatment groups, applied 1 kg Mo+40 kg S, 2 kg Mo+80 kg S, and 3 kg Mo+120 kg S per hectare for group I, group II, and group III, respectively. Seventy-two healthy Nanjiang brown goats (1 year old, 30.9 ± 1.1 kg) were randomly divided into 4 groups (3 replications/group, 6 goats/replication) and assigned to the tested pastures. The grazing experiment lasted for 60 days. The results showed that the contents of N, S, Mn, Zn, and Mo in herbage in fertilized pastures were higher than those in control group (P < 0.01). The contents of Cu and Se in herbage in fertilized pastures were lower than those in control group (P < 0.01). There were no differences among the fertilized pastures (P > 0.05). The contents of Mn, Zn, Mo, and S in serum and liver in the treatment goats were higher than those in control animals (P < 0.01). The contents of Cu and Se in serum and liver in the treatment goats were lower than those in control animals (P < 0.01). There was no difference in Fe and Co contents in herbage, serum, and liver among the four groups (P > 0.05). The levels of Hb, RBC, and PCV in blood in the treatment goats and the activities of SOD, GSH-Px, T-AOC, CAT, and Cp in serum were higher than those in control goats (P < 0.01). The contents of MDA in the treatment goats were lower than those in control animals (P < 0.01). The contents of serum Cu and Mo, and liver Cu in group III were lower than those in group I and group II (P < 0.01). Taken together, the combinations of S and Mo fertilization did not influence the mineral contents in herbage, serum, and liver, but reduced the toxicity of Cu in Cu-polluted grassland and improved antioxidant capacity in grazing Nanjiang brown goat from fertilized pastures.

5.
BMC Public Health ; 21(1): 551, 2021 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743630

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) confirmed cases overseas have continued to rise in the last months, and many people overseas have chosen to return to China. This increases the risk of a large number of imported cases which may cause a relapse of the COVID-19 outbreak. In order to prevent imported infection, the Shenzhen government has implemented a closed-loop management strategy using nucleic acid testing (NAT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and requiring 14 days of medical observation for individuals with an overseas tour history (Hong Kong, Macao, Taiwan province and other countries). Our study aims to describe the status of COVID-19 infection among people entering Shenzhen, and to evaluate the effect of the closed-loop management strategy. METHODS: We undertook a descriptive study and risk analysis by the entry time, time of reporting, and local confirmed cases in countries of origin. The NAT were completed in Shenzhen Center for Disease Control and Prevention (CDC), ten district-level CDCs, and fever clinics. RESULTS: A total of 86,844 people from overseas entered Shenzhen from January 1 to April 18, 2020; there were 39 imported COVID cases and 293 close contacts. The infection rate of people entering was 4.49‰ [95% Confidence interval (CI): 3.26‰-6.05‰]. Fourteen imported cases (35.9%) came from the UK, and nine (23.08%) came from the USA. People entering from the USA since March 9 or from the UK since March 13 are the high-risk population. As of July 17, there have been no new confirmed cases in Shenzhen for 153 days, and the numbers of confirmed case, close contacts, and asymptomatic cases are 0. CONCLUSIONS: The closed-loop management has been effective in preventing imported infection and controlling domestic relapse. The distribution of entry time and report time for imported cases overseas was similar. This shows that it is important to implement closed-loop management at the port of entry.


Assuntos
/epidemiologia , Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/prevenção & controle , China/epidemiologia , Humanos
6.
ACS Appl Mater Interfaces ; 13(12): 14543-14551, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33733728

RESUMO

Development of smart switchable surfaces to solve the inevitable bacteria attachment and colonization has attracted much attention; however, it proves very challenging to achieve on-demand regeneration for noncontaminated surfaces. We herein report a smart, host-guest interaction-mediated photo/temperature dual-controlled antibacterial surface, topologically combining stimuli-responsive polymers with nanobactericide. From the point of view of long-chain polymer design, the peculiar hydration layer generated by hydrophilic poly(2-hydroxyethyl methacrylate) (polyHEMA) segments severs the route of initial bacterial attachment and subsequent proliferation, while the synergistic effect on chain conformation transformation poly(N-isopropylacrylamide) (polyNIPAM) and guest complex dissociation azobenzene/cyclodextrin (Azo/CD) complex greatly promotes the on-demand bacterial release in response to the switch of temperature and UV light. Therefore, the resulting surface exhibits triple successive antimicrobial functions simultaneously: (i) resists ∼84.9% of initial bacterial attachment, (ii) kills ∼93.2% of inevitable bacteria attack, and (iii) releases over 94.9% of killed bacteria even after three cycles. The detailed results not only present a potential and promising strategy to develop renewable antibacterial surfaces with successive antimicrobial functions but also contribute a new antimicrobial platform to biomedical or surgical applications.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33684635

RESUMO

BACKGROUND: Chronic respiratory diseases (CRD) are common among patients with coronavirus disease 2019 (COVID-19). OBJECTIVES: We sought to determine the association between CRD (including disease overlap) and the clinical outcomes of COVID-19. METHODS: Data of diagnoses, comorbidities, medications, laboratory results, and clinical outcomes were extracted from the national COVID-19 reporting system. CRD was diagnosed based on International Classification of Diseases-10 codes. The primary endpoint was the composite outcome of needing invasive ventilation, admission to intensive care unit, or death within 30 days after hospitalization. The secondary endpoint was death within 30 days after hospitalization. RESULTS: We included 39,420 laboratory-confirmed patients from the electronic medical records as of May 6, 2020. Any CRD and CRD overlap was present in 2.8% and 0.2% of patients, respectively. Chronic obstructive pulmonary disease (COPD) was most common (56.6%), followed by bronchiectasis (27.9%) and asthma (21.7%). COPD-bronchiectasis overlap was the most common combination (50.7%), followed by COPD-asthma (36.2%) and asthma-bronchiectasis overlap (15.9%). After adjustment for age, sex, and other systemic comorbidities, patients with COPD (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.44-2.03) and asthma (OR: 1.45, 95% CI: 1.05-1.98), but not bronchiectasis, were more likely to reach to the composite endpoint compared with those without at day 30 after hospitalization. Patients with CRD were not associated with a greater likelihood of dying from COVID-19 compared with those without. Patients with CRD overlap did not have a greater risk of reaching the composite endpoint compared with those without. CONCLUSION: CRD was associated with the risk of reaching the composite endpoint, but not death, of COVID-19.

8.
Biomaterials ; 271: 120734, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33647873

RESUMO

Silver-based hybrid nanoprobes for surface-enhanced Raman scattering (SERS) imaging show their tremendous potential for precise biological detection and mediated phototherapy. However, the severe toxicity induced by Ag to normal mammalian cells hinders its further application. Herein, we presented a versatile bioinspired protein corona strategy through assembling bovine serum albumin (BSA) protected Raman tag DTTC-conjugated Ag-hybrid hollow Au nanoshells (hollow AgAu-DTTC-BSA), which their silver ion release and reactive oxygen species (ROS) generation are significantly suppressed, enabling no damage to normal cells and tissues, but can be reactivated on-demand under laser-irradiation at the tumor site. These nanoshells could also produce strong localized surface plasmon resonance for efficient-stable photothermal effect and enhanced SERS activity under laser irradiation, approved by both theoretical and experimental calculations. Furthermore, the biocompatible hollow AgAu-DTTC-BSA could detect both primary tumor tissues and tiny liver metastases (~0.18 mm) in orthotopic/subcutaneous CT26 colon tumor-bearing mice models. We also demonstrate their excellent therapeutic efficacy for colorectal solid neoplasms by accurate SERS imaging-guided photothermal therapy, simultaneously assisted with toxic Ag ion and ROS. These results suggest that hollow AgAu-DTTC-BSA is promising imaging assisted photothermal agents for solid tumor theranostics and enhancing the potential of Ag-based nanoparticles for practical treatment.

9.
Int J Infect Dis ; 106: 115-122, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33711518

RESUMO

OBJECTIVES: Tuberculous meningitis (TBM) is the most severe form of infection caused by Mycobacterium tuberculosis (Mtb). Smurf1 represents a key component in anti-Mtb autophagic targeting in macrophages and in anti-TB host defense in vivo. We hypothesized that genetic variants in the Smurf1 gene region influence susceptibility to TBM. METHODS: Using a case-control study design (235 TBM cases, 239 pulmonary TB cases and 478 healthy controls), we evaluated whether 8 haplotype-tagging single nucleotide polymorphisms (SNPs) in the Smurf1 gene are associated with the development of TBM. RESULTS: Even with the most conservative correction, the polymorphism rs6956450 was associated with TBM under a dominant model (odds ratio [OR], 1.653; 95% confidence interval [CI], 1.192-2.294; P = 0.021), the CG haplotype consisting of rs3294 and rs6956450 was positively associated with TBM (P = 0.013) and another haplotype GC remained negatively associated with TBM in Tibetan subgroup (P < 0.001). No correlation was found between rs6956450 and TBM clinical characteristics or prognosis. CONCLUSIONS: These results firstly link the variants in the Smurf1 gene region with TBM risk, indicating an important role for Smurf1 in the immunopathogenesis of TBM. Future studies will dissect the mechanism, which may help identify targets or genetic markers to guide diagnosis or host-directed therapy in patients with TBM.

10.
Mol Cell Probes ; 57: 101711, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33722663

RESUMO

BACKGROUND: Long non-coding RNA X-interactive specific transcript (XIST) is implicated in many diseases. However, its role and interaction with microRNA (miR)-499a-5p in intervertebral disc degeneration (IDD) remained unclear. METHODS: Nucleus pulposus (NP) tissue samples were collected and nucleus pulposus cells (NPCs) were isolated for Interleukin-1ß (IL-1ß) treatment and identification. XIST and miR-499a-5p expressions in the tissue were measured with quantitative real-time polymerase chain reaction (qRT-PCR). After IL-1ß treatment, NPC apoptosis was detected by flow cytometry. The potential binding sites of XIST and miR-499a-5p were predicted by starBase and confirmed by dual-luciferase reporter assay. Relative expressions of tissue inhibitor of metalloproteinases-3 (TIMP-3), Matrix metalloproteinases-3 (MMP-3), MMP-13, Collagen II, Aggrecan and apoptosis-related proteins (Bcl-2 associated X protein, Bax; B-cell lymphoma 2, Bcl-2; cleaved caspase-3) were measured by qRT-PCR and Western blot as needed. RESULTS: XIST expression was upregulated in the NP tissues of patients with IDD, and IL-1ß treatment resulted in a degradation of NPCs. Overexpressed XIST promoted the effects of IL-1ß on increasing NPC apoptosis and expressions of XIST, MMP-3, MMP-13, Bax and Cleaved caspase-3, but down-regulated TIMP-3, Collagen II, Aggrecan and Bcl-2 expressions. Silencing XIST, however, showed the opposite effects to its overexpression. MiR-499a-5p expression was downregulated in NP tissues of IDD patients and could bind with XIST, while its upregulation reversed the effects of overexpressed XIST in the IL-1ß-treated NPCs. CONCLUSION: Overexpressed XIST caused NPC degeneration through promoting apoptosis and extracellular matrix degradation of IL-1ß-treated NPCs through targeting miR-499a-5p, and therefore can serve as a potential treatment for IDD.

11.
J Adolesc Health ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33712380

RESUMO

PURPOSE: Medically ill youth are at increased risk for suicide. For convenience, hospitals may screen for suicide risk using depression screening instruments, though this practice might not be adequate to detect those at risk for suicide. This study aims to determine whether depression screening can detect suicide risk in pediatric medical inpatients who screen positive on suicide-specific measures. METHODS: A convenience sample of medical inpatients ages 10-21 years were recruited as part of a larger instrument validation study. Participants completed the Ask Suicide-Screening Questions, the Suicidal Ideation Questionnaire/Suicidal Ideation Questionnaire-Junior, and the Patient Health Questionnaire-Adolescent Version (PHQ-A). Univariate and multivariate statistics were calculated to examine the relationship between screening positive for depression and suicide risk. RESULTS: The sample consisted of 600 medical inpatients (59.2% female; 55.2% white; mean age 15.2 ± 2.84 years). Of participants who screened positive for suicide risk (13.5%; 81/600), 39.5% (32/81) did not screen positive for depression, and more than half (45/81) did not endorse PHQ-A item 9, which queries for thoughts of harming oneself or being better off dead. Twenty-six participants (32%) who screened negative for depression and on PHQ-A item nine were at risk for suicide. CONCLUSIONS: In this sample, depression screening alone failed to detect nearly a third of youth at risk for suicide. Although depression and suicide risk are strongly related, a significant portion of pediatric medical inpatients at risk for suicide may pass through the healthcare system unrecognized if depression screening is used as a proxy for identifying suicide risk.

12.
BMC Genomics ; 22(1): 217, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765915

RESUMO

BACKGROUND: Many recent studies have shown that miRNAs play important roles in the regulation of animal reproduction, including seasonal reproduction. The pineal gland is a crucial hub in the regulation of seasonal reproduction. However, little is known about the expression characteristics of pineal miRNAs in different reproductive seasons (anestrus and breeding season). Therefore, the expression profiles and regulatory roles of ovine pineal miRNAs were investigated during different reproductive stages using Solexa sequencing technology and dual luciferase reporter assays. RESULTS: A total of 427 miRNAs were identified in the sheep pineal gland. Significant differences in miRNA expression were demonstrated between anestrus and the breeding season in terms of the frequency distributions of miRNA lengths, number of expressed miRNAs, and specifically and highly expressed miRNAs in each reproductive stage. KEGG analysis of the differentially expressed (DE) miRNAs between anestrus and the breeding season indicated that they are significantly enriched in pathways related to protein synthesis, secretion and uptake. Furthermore, transcriptome analysis revealed that many target genes of DE miRNAs in the ribosome pathway showed relatively low expression in the breeding season. On the other hand, analyses combining miRNA-gene expression data with target relationship validation in vitro implied that miR-89 may participate in the negative regulation of aralkylamine N-acetyltransferase (AANAT) mRNA expression by targeting its 3'UTR at a unique binding site. CONCLUSIONS: Our results provide new insights into the expression characteristics of sheep pineal miRNAs at different reproductive stages and into the negative regulatory effects of pineal miRNAs on AANAT mRNA expression.

13.
Sci Rep ; 11(1): 6933, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767315

RESUMO

To explore the value of contrast-enhanced CT texture analysis in predicting isocitrate dehydrogenase (IDH) mutation status of intrahepatic cholangiocarcinomas (ICCs). Institutional review board approved this study. Contrast-enhanced CT images of 138 ICC patients (21 with IDH mutation and 117 without IDH mutation) were retrospectively reviewed. Texture analysis was performed for each lesion and compared between ICCs with and without IDH mutation. All textural features in each phase and combinations of textural features (p < 0.05) by Mann-Whitney U tests were separately used to train multiple support vector machine (SVM) classifiers. The classification generalizability and performance were evaluated using a tenfold cross-validation scheme. Among plain, arterial phase (AP), portal venous phase (VP), equilibrium phase (EP) and Sig classifiers, VP classifier showed the highest accuracy of 0.863 (sensitivity, 0.727; specificity, 0.885), with a mean area under the receiver operating characteristic curve of 0.813 in predicting IDH mutation in validation cohort. Texture features of CT images in portal venous phase could predict IDH mutation status of ICCs with SVM classifier preoperatively.

14.
Taiwan J Obstet Gynecol ; 60(2): 318-323, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33678334

RESUMO

OBJECTIVE: The aim of this work was to characterize the genetic abnormalities and prenatal diagnosis indications in one fetus with Cri-du-Chat syndrome with codependent 10q24.2-q26.3 duplication in prenatal screening. MATERIALS AND METHODS: A 31-year-old woman had a second trimester serum screening that indicated the fetus was at low risk. During this pregnancy, the woman underwent amniocentesis at 18+4 weeks' gestation because of adverse fertility history and nuchal fold thickening. Cytogenetic analysis and next-generation sequencing analysis were simultaneously performed to provide genetic analysis of fetal amniotic fluid. According to abnormal results, parental chromosome karyotype of peripheral blood was performed to analysis. RESULTS: CNV-seq detected a 14.00 Mb deletion at 5p15.33-p15.2 and a 34.06 Mb duplication at 10q24.2-q26.3 in the fetus. Cytogenetic analysis of the fetus revealed a karyotype of 46, XY, der(5) t(5;10) (p15.2;q26.3). The karyotype of pregnant women was 46,XX,t(5;10) (p15.2;q24.2). The pregnancy was subsequently terminated after sufficient informed consent. CONCLUSION: This is the first study that reports prenatal diagnosis of a Cri-du-Chat syndrome with concomitant 10 q24.2-q26.3 duplication. Adverse pregnancy history has to be as an important indicator for prenatal diagnosis, and the genetic factors of abnormal pregnancy should be identified before next pregnancy. Nuchal fold thickening is closely related to fetal abnormalities. Combined with ultrasonography, the use of CNV-seq will improve the diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital anomalies.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33721086

RESUMO

The objective of this study is to examine the association between headache and mental disorders in a nationally representative sample of American youth. We used the National Comorbidity Survey-Adolescent Supplement to assess sex-specific prevalence of lifetime migraine and non-migraine headache using modified International Headache Society criteria and examine associations between headache subtypes and DSM-IV mental disorders. Adolescent report (n = 10,123) was used to identify headache subtypes and anxiety, mood, eating, and substance use disorders. ADHD and behavior disorder were based on parent report (n = 6483). Multivariate logistic regression analyses controlling for key demographic characteristics were used to examine associations between headache and mental disorders. Headache was endorsed by 26.9% (SE = 0.7) of the total sample and was more prevalent among females. Youth with headache were more than twice as likely (OR 2.74, 95% CI 1.94-3.83) to meet criteria for a DSM-IV disorder. Migraine, particularly with aura, was associated with depression and anxiety (adjusted OR 1.90-2.90) and with multiple classes of disorders. Adolescent headache, particularly migraine, is associated with anxiety, mood, and behavior disorders in a nationally representative sample of US youth. Headache is highly prevalent among youth with mental disorders, and youth with headache should be assessed for comorbid depression and anxiety that may influence treatment, severity, and course of both headache and mental disorders.

16.
Cell Prolif ; : e13031, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755268

RESUMO

OBJECTIVES: ZFP91, an E3 ligase, has been reported to possess cancer-promoting functions. This study aimed to elucidate the exact role of ZFP91 in tumour progression of pancreatic cancer and underlying mechanisms. MATERIALS AND METHODS: We analysed the correlation between ZFP91 expression and pancreatic cancer through TCGA and GEO data sets. Growth curve, colony formation, wound healing and transwell invasion assays were conducted to evaluate proliferation, migration and invasion of lentivirus transfected pancreatic cancer cells. GSEA and Western blot analysis were performed to validate the regulatory effect of ZFP91 on ß-catenin. Drug response curve and orthotopic implantation model reflected the sensitivity of chemotherapies. RESULTS: ZFP91 overexpression is prevalent in pancreatic cancer and negatively correlated with overall survival. ZFP91 knock-down attenuated proliferation, migration and invasion of pancreatic cancer cells. ß-catenin was a downstream gene of ZFP91, and its agonist could reverse the phenotype. ZFP91 promoted EMT and chemoresistance in pancreatic cancer. CONCLUSIONS: We demonstrated that ZFP91 promoted pancreatic cancer proliferation, migration and invasion through activating ß-catenin signalling. EMT and chemoresistance were also regulated by ZFP91. ZFP91 might be a potential therapeutic target for pancreatic cancer.

17.
Pain Res Manag ; 2021: 6644262, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33727997

RESUMO

Background and Objectives. Several anesthesia techniques were applied to hemorrhoidectomy, but postoperative pain and urinary retention were still two unsolved problems. The aim of this prospective randomized study was to evaluate the effect of ultrasound-guided pudendal nerve block (PNB) combined with deep sedation compared to spinal anesthesia for hemorrhoidectomy. Methods. One hundred and twenty patients undergoing Milligan-Morgan hemorrhoidectomy were randomized to receive PNB combined with deep sedation using propofol (Group PNB, n = 60) or spinal anesthesia (Group SA, n = 60). Pain intensity was assessed using the visual analogue scale (0: no pain to 10: worst possible pain). The primary outcome was pain scores recorded at rest at 3, 6, 12, 24, 36, and 48 h and on walking at 12, 24, 36, and 48 h postoperatively. Secondary outcomes were analgesic consumption, side effects, and patient satisfaction after surgery. Results. Ultrasound-guided bilateral PNB combined with deep sedation using propofol could successfully be applied to Milligan-Morgan hemorrhoidectomy. Postoperative pain intensity was significantly lower in Group PNB compared to Group SA at rest at 3, 6, 12, 24, 36, and 48 h (p < 0.001) and during mobilization at 12, 24, 36, and 48 h (p < 0.001) postoperatively. Sufentanil consumption in Group PNB was significantly lower than that in Group SA, during 0-24 h (p < 0.001) and during 24-48 h (p < 0.001) postoperatively. Urinary retention was significantly lower in Group PNB compared to Group SA (6.9% vs 20%, p=0.034). The patients in Group PNB had higher satisfaction compared to Group SA (p < 0.001). Conclusions. Ultrasound-guided PNB combined with propofol sedation is an effective anesthesia technique for Milligan-Morgan hemorrhoidectomy.

18.
J Clin Child Adolesc Psychol ; : 1-12, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656940

RESUMO

Objective: To examine cross-sectional associations between social capital constructs and 1) adolescent lifetime mental disorders, 2) severity of functional impairment, and 3) psychiatric comorbidity.Method: Data were from the National Comorbidity Survey Adolescent Supplement, a nationally representative mental health survey of 6,483 U.S. adolescents aged 13-18 years. Information from fully-structured diagnostic interviews, including adolescent and caregiver reports, was used to measure seven social capital constructs and lifetime DSM-IV mental disorders (mood, anxiety, behavior, substance use and eating disorder classes). Disorder severity was divided into severe vs. mild/moderate. Comorbidity was measured as the number of different classes of lifetime mental disorders.Results: Adjusted for socio-demographics and caregivers' mental health, the most consistent associations with adolescent mental disorder were for supportive friendships (any disorder OR = 0.95, 95%CI = 0.91-0.99), family cohesion (OR = 0.81, 95%CI = 0.75-0.86), school bonding (OR = 0.76, 95%CI = 0.71-0.81), and extracurricular participation (OR = 0.90, 95%CI = 0.86-0.95), although results differed by disorder class. Caregiver-reported neighborhood trust and reciprocity and caregiver community involvement were less consistently associated with mental disorder. Medium levels of adolescent-reported affiliation with neighbors was associated with lower odds of mood (OR = 0.81, 95%CI = 0.66-0.98) and anxiety (OR = 0.78, 95%CI = 0.64-0.96) disorder, while high levels were associated with higher odds of behavior disorder (OR = 1.47, 95%CI = 1.16-1.87). Several associations were stronger for severe vs. mild/moderate disorder and with increasing comorbidity.Conclusion: Although we cannot infer causality, our findings support the notion that improving actual and/or perceived social capital, especially regarding friendships, family, and school, (e.g., through multimodal interventions) could aid in the prevention and treatment of both individual adolescent mental disorders and psychiatric comorbidity.

19.
J Struct Biol ; 213(2): 107710, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33610655

RESUMO

KW-2478 is a promising anti-cancer lead compound targeting to the molecular chaperone heat shock protein 90 N (Hsp90N). Absence of complex crystal structure of Hsp90N-KW-2478, however, hampered further structure optimization of KW-2478 and understanding on the molecular interaction mechanism. Herein, a high-resolution complex crystal structure of Hsp90N-KW-2478 was determined by X-ray diffraction (XRD, resolution limit: 1.59 Å; PDB ID: 6LT8) and their molecular interaction was analyzed in detail, which suggested that KW-2478 perfectly bound in the N-terminal ATP-binding pocket of Hsp90 to disable its molecular chaperone function, therefore suppressed or killed cancer cells. The results from thermal shift assay (TSA, ΔTm, 18.82 ± 0.51 °C) and isothermal titration calorimetry (ITC, Kd, 7.30 ± 2.20 nM) suggested that there is an intense binding force and favorable thermodynamic changes during the process of KW-2478 binding with Hsp90N. Additionally, KW-2478 exhibited favorable anti-NSCLC activity in vitro, as it inhibited cell proliferation (IC50, 8.16 µM for A549; 14.29 µM for H1975) and migration, induced cell cycle arrest and promoted apoptosis. Thirty-six novel KW-2478 derivatives were designed, based on the complex crystal structure and molecular interaction analysis of Hsp90N-KW-2478 complex. Among them, twenty-two derivatives exhibited increased binding force with Hsp90N evaluated by molecular docking assay. The results would provide new guidance for anti-NSCLC new drug development based on the lead compound KW-2478.

20.
J Nat Prod ; 84(2): 537-543, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33631936

RESUMO

A new bafilomycin derivative (1) and another seven known bafilomycins (2-8) were isolated from feces-derived Streptomyces sp. HTL16. The structure of 1 was elucidated by 1D and 2D NMR spectroscopic analysis. Biological testing demonstrated that these bafilomycins exhibited potent antiviral activities against the influenza A and SARS-CoV-2 viruses, with IC50 values in the nanomolar range, by inhibiting the activity of endosomal ATP-driven proton pumps.


Assuntos
Antivirais/farmacologia , Fezes/microbiologia , Macrolídeos/farmacologia , ATPases Translocadoras de Prótons/antagonistas & inibidores , Streptomyces/metabolismo , Animais , Cães , Vírus da Influenza A/efeitos dos fármacos , Células Madin Darby de Rim Canino , /efeitos dos fármacos
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