Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 210
Filtrar
1.
J Virol ; : JVI0182721, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020472

RESUMO

Human cytomegalovirus (HCMV) has a large (∼235-kb) genome with over 200 predicted open reading frames and exploits numerous cellular factors to facilitate its replication. A key feature of HCMV-infected cells is the emergence of a distinctive membranous cytoplasmic compartment termed the virion assembly compartment (vAC). Here we report that host protein WD repeat domain 11 (WDR11) plays a key role in vAC formation and virion morphogenesis. We found that WDR11 was up-regulated at both mRNA and protein levels during HCMV infection. At the late stage of HCMV replication, WDR11 relocated to the vAC and co-localized with markers of the trans-Golgi network (TGN) and vAC. Depletion of WDR11 hindered HCMV-induced membrane reorganization of the Golgi and TGN, altered vAC formation, and impaired HCMV secondary envelopment and virion morphogenesis. Further, motifs critical for the localization of WDR11 in TGN were identified by alanine-scanning mutagenesis. Mutation of these motifs led to WDR11 mislocation outside of the TGN and loss of vAC formation. Taken together, these data indicate that host protein WDR11 is required for efficient viral replication at the stage of virion assembly, possibly by facilitating the remodeling of the endomembrane system for vAC formation and virion morphogenesis. Importance During the late phase of human cytomegalovirus (HCMV) infection, the endomembrane system is dramatically reorganized, resulting in the formation of a unique structure termed the virion assembly compartment (vAC), which is critical for the assembly of infectious virions. The mechanism of HCMV-induced vAC formation is still not fully understood. In this report, we identified a host factor, WDR11, that plays an important role in vAC formation. Our findings argue that WDR11 contributes to the relocation of the Golgi and trans-Golgi network to the vAC, a membrane reorganization process that appears to be required for efficient virion maturation. The present work provides new insights into the vAC formation and HCMV virion morphogenesis and a potential novel target for anti-viral treatment.

2.
JCI Insight ; 7(1)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014624

RESUMO

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.

3.
J Card Surg ; 37(1): 53-61, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34657299

RESUMO

BACKGROUND: Acute type A aortic dissection (ATAAD) is life-threatening and requires immediate surgery. Sudden chest pain may lead to a risk of misdiagnosis as an acute coronary syndrome and may lead to subsequent antiplatelet therapy (APT). We used the Chinese Acute Aortic Syndrome (AAS) Collaboration Database to study the effects of APT on clinical outcomes. METHODS: The AAS database is a retrospective multicentre database where 31 of 3092 patients had APT with aspirin or clopidogrel or both before surgery. Before and after propensity score matching (PSM), the incidence of complications and mortality was compared between APT and non-APT patients by using a logistic regression model. The sample remaining after PSM was 30 in the APT group and 80 in the non-APT group. RESULTS: The sample remaining after matching was 30 in the APT group and 80 in the non-APT group. We found 10 cases with percutaneous coronary intervention in the APT group (33.3%). The APT group received more volume of packed red blood cells, 8.4 ± 6.05 units; plasma, 401.67 ± 727 ml, and platelet transfusion (14.07 ± 8.92 units). The drainage volume was much more in the APT group (5009.37 ± 2131.44 ml, p = .004). Mortality was higher in APT group (26% vs. 10%, p = .027). The preoperative APT was an independent predictor of mortality (odds ratio: 6.808, 95% confidence interval: 1.554-29.828, p = .011). CONCLUSION: APT before ATAAD repair was associated with more transfusions and higher early mortality. The timing of surgery should be carefully considered based on the patient's status and the surgeon's experience.


Assuntos
Aneurisma Dissecante , Inibidores da Agregação Plaquetária , Aneurisma Dissecante/cirurgia , Aspirina , Clopidogrel , Humanos , Estudos Retrospectivos
4.
Adipocyte ; 11(1): 47-55, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34957917

RESUMO

Retinoic acid (RA), a bioactive metabolite of vitamin A, has shown therapeutic effects in liver disease, and its effect in improving non-alcoholic fatty liver disease (NAFLD) is associated with the inhibition of adipogenesis in the white adipose tissue (WAT) and fatty acid oxidation induction in the liver. However, the major target organ of RA is unknown. We performed chronic administration of RA in high-fat diet (HFD)-induced NAFLD mice. Further, hepatic and adipose cells were used to study the direct effect of RA on lipid metabolism. In addition, qRT-PCR was performed to examine differential gene expression in mouse adipose tissue. RA administration ameliorated NAFLD in HFD-induced obese mice and increased mouse energy expenditure. Although RA had therapeutic effects on liver histology and lipid accumulation, it did not directly affect lipid metabolism in HepG2 cells. In contrast, RA reduced the weight of several adipose tissues and improved lipid accumulation in OP9 cells. In addition, RA upregulated genes responsible for fatty acid oxidation and thermogenesis in three different WATs. Our work suggests that the liver may not be the main target organ of RA during NAFLD treatment. WAT browning induced by RA may be the primary contributor towards the amelioration of NAFLD in HFD-induced obese mice.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Tretinoína , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Termogênese , Tretinoína/metabolismo , Tretinoína/farmacologia
5.
Front Cardiovasc Med ; 8: 782235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34881315

RESUMO

We herein present a case of infective endocarditis of the mitral valve and a paravalvular abscess around the tricuspid valve. Preoperative blood culture confirmed the presence of pathogenic diphtheroids. During the operation, an unexpected infection of the free wall of the right atrium (RA) near the tricuspid annulus was found. We harvested the left atrial appendage (LAA) en bloc. After resection of the infected and abnormal tissues, the resected LAA was used to reconstruct the RA. The infected mitral valve was replaced with a mechanical valve without any accident. Postoperative echocardiography showed that the RA had a supple shape, with no kinking.

6.
J Am Coll Cardiol ; 78(23): e293, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34857101
7.
Chem Commun (Camb) ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34843613

RESUMO

Transition metal-catalyzed cycloaddition has been established as a powerful tool for heterocycle synthesis. Despite impressive advances, the exploitation of new catalysis strategies and systems is still highly significant to enrich the heterocycle family. Herein, we disclosed a cooperative catalysis system merging an achiral Pd catalyst and a chiral Co catalyst for the asymmetric [4+2] cycloaddition between vinyl benzoxazinones and N-acylpyrazoles. Chiral tetrahydroquinolines bearing two contiguous, unusual cis-configured stereocenters were produced in high yields and enantio- and diastereoselectivities. The pyrazole directing group can be easily converted into many other functional groups, thus demonstrating the flexibility of the present methodology.

8.
Adipocyte ; 10(1): 646-657, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34793269

RESUMO

Obesity and associated complications are becoming a pandemic. Inhibiting adipogenesis is an important intervention for the treatment of obesity. Despite intensive investigations, numerous mechanistic aspects of adipogenesis remain unclear, and many potential therapeutic targets have yet to be discovered. Transcriptomics and lipidomics approaches were used to explore the functional genes regulating adipogenic differentiation and the potential mechanism in OP9 cells and adipose-derived stem cells. In this study, we found that NADH:ubiquinone oxidoreductase subunit A6 (Ndufa6) participates in the regulation of adipogenic differentiation. Furthermore, we show that the effect of Ndufa6 is mediated through stearoyl-CoA desaturase 1 (Scd1) and demonstrate the inhibitory effect of a SCD1 inhibitor on adipogenesis. Our study broadens the understanding of adipogenic differentiation and offers NDUFA6-SCD1 as a potential therapeutic target for the treatment of obesity.

9.
J Virol ; : JVI0147621, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730396

RESUMO

Human cytomegalovirus (HCMV) establishes a persistent/latent infection after primary infection, and host factor(s) plays a key role in regulating HCMV infection status. The spread of reactivated HCMV via the hematogenous or neural route usually results in severe diseases in newborns and immunocompromised individuals. As the primary reservoirs in vivo, cells of myeloid lineage have been utilized extensively to study HCMV infection. However, the molecular mechanism of HCMV latency/reactivation in neural cells is still poorly understood. We previously showed that HCMV infected T98G cells maintain a large number of viral genomes and support HCMV reactivation from latency upon cAMP/IBMX treatment. Here we employed iTRAQ-based proteomics to characterize cellular protein changes during HCMV latency and reactivation in T98G cells. A total of 168 differentially expressed proteins (DEPs) were identified, including 89 proteins in latency and 85 proteins in reactivation. Bioinformatics analysis showed that a few biological pathways were associated with HCMV latency or reactivation. Moreover, we validated 16 DEPs by both mRNA and protein expression profiles and further evaluated the effects of ApoE and PI3K pathway on HCMV infection. ApoE knockdown reduced HCMV loads and virus release, whereas overexpressing ApoE hampered HCMV latent infection, indicating a role in HCMV latency establishment/maintenance. Blocking the PI3K pathway by LY294002, a PI3K inhibitor, induced HCMV reactivation from latency in T98G cells. Overall, this comparative proteomic analysis delineates the cellular protein changes during HCMV latency and reactivation and provides a road map to advance our understanding of the mechanism(s) in the context of neural cells. IMPORTANCE Human cytomegalovirus (HCMV) is a highly transmissible beta-herpesvirus that has a prevalence of 60%-90% worldwide. This opportunist pathogen poses a significant threat to newborns and immunosuppressed individuals. One major obstacle for developing effective therapeutics is a poor understanding of HCMV latency/reactivation mechanisms. This study presents, for the first time, a systemic analysis of host cell protein expression changes during HCMV latency establishment and reactivation processes in neural cells. We showed that ApoE was downregulated by HCMV to facilitate latent infection. Also, the proteomic analysis has associated a few PI3K pathway-related proteins with HCMV reactivation. Altogether, this study highlights multiple host proteins and signaling pathways that can be further investigated as potential druggable targets for HCMV-related diseases, especially brain disorders.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34657171

RESUMO

INTRODUCTION: Single-agent immune checkpoint inhibitors (ICIs) like pembrolizumab or atezolizumab have been approved as first-line monotherapy for advanced non-small cell lung cancer (NSCLC) patients with PD-L1 ≥ 50%. However, emerging evidences have showed that ICI combinations (chemoimmunotherapy or dual-agent ICIs) argue to offer a higher response rate. In this network meta-analysis, we aimed to evaluate the efficacy and toxicity of first-line single-agent ICIs versus ICI combinations for advanced NSCLC patients with PD-L1 ≥ 50%. METHODS: PubMed, Embase, Cochrane Library and the Clinicaltrials.gov were systematically searched to extract eligible literature until December 2020. Outcomes included overall survival (OS), progression free survival (PFS), objective response rate (ORR) and treatment related adverse events (TRAEs) of grades 3-5. RESULTS: Fourteen studies with 3448 patients were included. The results showed that chemotherapy plus ICIs significantly improved PFS and ORR compared to chemotherapy, and sinti-chemo (HR: 0.31, 95% CI: 0.20-0.49) and pembro-chemo (OR: 4.2, 95% CI: 2.6-6.7) ranked first. In terms of OS, cemiplimab provided the best benefit versus chemotherapy (HR: 0.57, 95% CI: 0.43-0.77), followed by atezolizumab and pembro-chemo. In the subgroup analysis of histological type, pembro-chemo and sinti-chemo showed the best benefit of PFS in squamous and nonsquamous NSCLC, respectively, while there was no significant difference between ICI combinations with single-agent ICIs in OS. Moreover, the addition of chemotherapy to ICIs elevated toxicity compared to chemotherapy. CONCLUSION: The study suggested that chemotherapy plus ICIs might improve PFS and ORR than single-agent ICIs for advanced NSCLC patients with PD-L1 ≥ 50%. However, it did not lead to OS benefit.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34695600

RESUMO

COVID-19 has swept globally and Pakistan is no exception. To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan, we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected before June 2, 2020. We identified a total of 347 mutated positions, 31 of which were over-represented in Pakistan. Meanwhile, we found over 1000 intra-host single-nucleotide variants (iSNVs). Several of them occurred concurrently, indicating possible interactions among them or coevolution. Some of the high-frequency iSNVs in Pakistan were not observed in the global population, suggesting strong purifying selections. The genomic epidemiology revealed five distinctive spreading clusters. The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure, indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation (G8371T in ORF1ab) of this cluster. Furthermore, 28 putative international introductions were identified, several of which are consistent with the epidemiological investigations. In all, this study has inferred the possible pathways of introduction and transmissions of SARS-CoV-2 in Pakistan, which could aid ongoing and future viral surveillance and COVID-19 control.

12.
Invest Ophthalmol Vis Sci ; 62(13): 22, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34698772

RESUMO

Purpose: Considering the difficulty of obtaining adequate biological tissue in clinical practice, we established an animal model of cytomegalovirus (CMV) keratouveitis in rats and investigated the viral infection sites and corresponding imaging and histopathological features. Methods: Subconjunctival injection and topical use of dexamethasone were used to induce ocular immunosuppression in rats followed by intracameral inoculation of murine cytomegalovirus (MCMV). The clinical manifestations, intraocular pressure (IOP) and imaging changes were observed. Infected eyes were further examined by immunofluorescence, light microscopy, and electron microscopy. MCMV RNA was detected by reverse transcription-polymerase chain reaction. Results: Typical keratouveitis occurred in the experimental rats and was characterized by corneal edema, keratic precipitates, and iridocyclitis with increased IOP. Corneal endothelial lesions displayed as "black holes," enlarged intercellular gaps, and high-intensity cellular infiltration by confocal microscopy, consistent with the pathological changes of "ballooning degeneration," endothelial cell detachment, and inflammatory cell infiltration. Mitochondrial edema was the most prominent organelle lesion in endothelial cells. Trabeculitis, mechanical obstruction of Schlemm's canal, and anterior chamber angle stenosis accounted for elevated IOP. Inflammation of the iris and ciliary body tended to transform into a chronic form. Immunofluorescence revealed that corneal endothelial cells, iris cells, trabecular meshwork cells, and monocytes could be infected by MCMV. MCMV RNA was found in the anterior segments after infection. Conclusions: CMV can widely infect anterior segment tissue, including the corneal endothelium, iris, and trabecular meshwork, in vivo, inducing the corresponding clinical manifestations. Corneal endotheliitis and hypertensive anterior uveitis could be the specific stage of anterior segment infection of CMV.


Assuntos
Segmento Anterior do Olho/virologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/genética , DNA Viral/análise , Infecções Oculares Virais/virologia , Uveíte Anterior/virologia , Animais , Segmento Anterior do Olho/diagnóstico por imagem , Humor Aquoso/virologia , Infecções por Citomegalovirus/diagnóstico , Modelos Animais de Doenças , Endotélio Corneano/patologia , Endotélio Corneano/virologia , Infecções Oculares Virais/diagnóstico , Feminino , Ratos , Ratos Sprague-Dawley , Uveíte Anterior/diagnóstico
13.
Chem Soc Rev ; 50(22): 12808-12827, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652345

RESUMO

Transition metal-catalysed asymmetric coupling has been established as a robust tool for constructing complex organic molecules. Although this area has been extensively studied, the development of efficient protocols to construct stereogenic centres with excellent regio- and enantioselectivities is highly desirable and remains challenging. Asymmetric transition metal catalysis with light intervention provides a practical alternative strategy to current methods and considerably expands the synthetic utility as a result of abundant feedstocks and mild conditions. This tutorial review comprehensively summarizes the recent advances in transition-metal-catalysed asymmetric coupling reactions with light intervention; in particular, a concise analysis of substrate scope and the mechanistic scenarios governing stereocontrol is discussed.

14.
PLoS One ; 16(9): e0257309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34587169

RESUMO

This paper uses newly available data from Web of Science on publications matched to researchers in Survey of Doctorate Recipients to compare the quality of scientific publication data collected by surveys versus algorithmic approaches. We illustrate the different types of measurement errors in self-reported and machine-generated data by estimating how publication measures from the two approaches are related to career outcomes (e.g., salaries and faculty rankings). We find that the potential biases in the self-reports are smaller relative to the algorithmic data. Moreover, the errors in the two approaches are quite intuitive: the measurement errors in algorithmic data are mainly due to the accuracy of matching, which primarily depends on the frequency of names and the data that was available to make matches, while the noise in self reports increases over the career as researchers' publication records become more complex, harder to recall, and less immediately relevant for career progress. At a methodological level, we show how the approaches can be evaluated using accepted statistical methods without gold standard data. We also provide guidance on how to use the new linked data.

15.
JCI Insight ; 6(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34383712

RESUMO

Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and main indication for heart transplantation in children. Therapies specific to pediatric DCM remain limited due to lack of a disease model. Our previous study showed that treatment of neonatal rat ventricular myocytes (NRVMs) with serum from nonfailing or DCM pediatric patients activates the fetal gene program (FGP). Here we show that serum treatment with proteinase K prevents activation of the FGP, whereas RNase treatment exacerbates it, suggesting that circulating proteins, but not circulating miRNAs, promote these pathological changes. Evaluation of the protein secretome showed that midkine (MDK) is upregulated in DCM serum, and NRVM treatment with MDK activates the FGP. Changes in gene expression in serum-treated NRVMs, evaluated by next-generation RNA-Seq, indicated extracellular matrix remodeling and focal adhesion pathways were upregulated in pediatric DCM serum and in DCM serum-treated NRVMs, suggesting alterations in cellular stiffness. Cellular stiffness was evaluated by Atomic Force Microscopy, which showed an increase in stiffness in DCM serum-treated NRVMs. Of the proteins increased in DCM sera, secreted frizzled-related protein 1 (sFRP1) was a potential candidate for the increase in cellular stiffness, and sFRP1 treatment of NRVMs recapitulated the increase in cellular stiffness observed in response to DCM serum treatment. Our results show that serum circulating proteins promoted pathological changes in gene expression and cellular stiffness, and circulating miRNAs were protective against pathological changes.

16.
J Womens Health (Larchmt) ; 30(11): 1546-1555, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34448599

RESUMO

Objective: The outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens a surging number of community groups within society, including women actively breastfeeding. Breastfeeding involves intimate behaviors, a major transmission route of SARS-CoV-2, and is integral to the close mother-baby relationship highly correlated with maternal psychological status. Materials and Methods: Twenty-three pregnant women and puerperae with either confirmed or suspected diagnoses of COVID-19 were enrolled in the study. The clinical characteristics and outcomes of the mothers and neonates were recorded. The presence of SARS-CoV-2, IgG, and IgM in breast milk, maternal blood, and infant blood, together with feeding patterns, was assessed within 1 month after delivery. Feeding patterns and maternal psychological status were also recorded in the second follow-up. Results: No positive detection of SARS-CoV-2 was found in neonates. All breast milk samples were negative for the detection of SARS-CoV-2. The presence of IgM for SARS-CoV-2 in breast milk was correlated with IgM presence in the maternal blood. The results of IgG detection for SARS-CoV-2 were negative in all breast milk samples. All infants were in a healthy condition in two follow-ups, and antibody tests for SARS-CoV-2 were negative. The rate of breast milk feeding increased during two follow-ups. All mothers receiving a second follow-up experienced negative psychological factors and status. Conclusions: Our findings support the feasibility of breastfeeding in women infected with SARS-CoV-2. The additional negative psychological status of mothers due to COVID-19 should also be considered during the puerperium period.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Aleitamento Materno , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Laboratórios , Mães , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , SARS-CoV-2
17.
J Int Med Res ; 49(6): 3000605211013548, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34187214

RESUMO

OBJECTIVE: Long non-coding RNA (lncRNA) expression is closely related to the pathogenesis and progression of various tumors. In this study, we investigated the mechanisms of lncRNA HOXB cluster antisense RNA 3 (HOXB-AS3), miRNA(miR)-498-5p, and disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) in endometrial carcinoma (EC) cells. METHODS: The expression levels of lncRNA HOXB-AS3 in EC tissues and cells were detected using RT-qPCR assays. The effects of HOXB-AS3 knockdown on EC cell proliferation and apoptosis were measured using CCK-8 assays, colony formation assays, and flow cytometry. In addition, putative miR-498-5p binding sites were identified in HOXB-AS3 and ADAM9. The targeted relationships were further verified using dual-luciferase reporter and RNA pull-down assays. RESULTS: HOXB-AS3 expression was upregulated in EC tissues and cells. EC cell proliferation and viability decreased significantly in HOXB-AS3 knockdown groups. A putative miR-498-5p binding site in HOXB-AS3 was verified. Inhibition of miR-498-5p rescued the effects of HOXB-AS3 knockdown on cell proliferation and apoptosis. Finally, ADAM9 was verified as a direct target gene of miR-498-5p. CONCLUSIONS: Our results suggest that lncRNA HOXB-AS3 is highly expressed in EC tissues and cells. Downregulation of HOXB-AS3 inhibits cell proliferation and promotes apoptosis in EC cells. HOXB-AS3 can upregulate ADAM9 expression by sponging miR-498-5p.


Assuntos
Neoplasias do Endométrio , MicroRNAs , RNA Longo não Codificante , Proteínas ADAM/genética , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias do Endométrio/genética , Feminino , Proteínas de Homeodomínio , Humanos , Proteínas de Membrana/genética , MicroRNAs/genética , RNA Longo não Codificante/genética
19.
Aging (Albany NY) ; 13(12): 15770-15784, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168096

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and is highly contagious and pathogenic. TMPRSS2 and Neuropilin-1, the key components that facilitate SARS-CoV-2 infection, are potential targets for treatment of COVID-19. Here we performed a comprehensive analysis on NRP1 and TMPRSS2 in lung to provide information for treating comorbidity of COVID-19 with lung cancer. NRP1 is widely expressed across all the human tissues while TMPRSS2 is expressed in a restricted pattern. High level of NRP1 associates with worse prognosis in multiple cancers, while high level of TMPRSS2 is associated with better survival of Lung Adenocarcinoma (LUAD). Moreover, NRP1 positively correlates with the oncogenic Cancer Associated Fibroblast (CAF), macrophage and endothelial cells infiltration, negatively correlates with infiltration of CD8+ T cell, the tumor killer cell in Lung Squamous cell carcinoma (LUSC). TMPRSS2 shows negative correlation with the oncogenic events in LUAD. RNA-seq data show that NRP1 level is slightly decreased in peripheral blood of ICU admitted COVID-19 patients, unaltered in lung, while TMPRSS2 level is significantly decreased in lung of COVID-19 patients. Our analysis suggests NRP1 as a potential therapeutic target, while sets an alert on targeting TMPRSS2 for treating comorbidity of COVID-19 and lung cancers.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Neuropilina-1/fisiologia , Serina Endopeptidases/fisiologia , Adenocarcinoma de Pulmão/mortalidade , Linfócitos T CD8-Positivos/metabolismo , COVID-19/genética , COVID-19/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Simulação por Computador , Células Endoteliais/metabolismo , Humanos , Neoplasias Pulmonares/mortalidade , Macrófagos/metabolismo , Neuropilina-1/genética , RNA-Seq , SARS-CoV-2 , Serina Endopeptidases/genética
20.
Am J Transl Res ; 13(4): 3369-3379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017512

RESUMO

OBJECTIVE: This research was designed to probe into the influencing factors of holistic nursing intervention under a social medical model on psychology and quality of life in advanced gastric cancer (GC) patients. METHODS: Altogether 194 patients with advanced GC treated in our hospital from May 2017 to July 2018 were divided into two groups according to different nursing intervention methods. Where from, 86 were given routine nursing intervention and 108 were given holistic nursing intervention under a social medical model. The psychology, pain relief, sleep quality and self-nursing ability of patients were compared before and after intervention. The quality of life before and after intervention and the nursing satisfaction score after nursing were recorded. The factors affecting their quality of life were assessed by Logistic regression analysis. RESULTS: The SAS, SDS, NRS and PSQI scores in the intervention group (IG) were obviously lower than those in the control group (CG) after nursing. The ESCA and EORTC QLQ-C30 scores after nursing in the IG were markedly higher than those in the CG. The total nursing satisfaction of patients in the IG after nursing was obviously higher than that in the CG. Logistic regression analysis revealed that age, lymph node metastasis, TNM stage, unimproved negative emotion, lack of self-nursing ability and routine nursing intervention all increased the risk of reduced quality of life. CONCLUSION: The decline in the quality of life of patients with advanced GC results from a comprehensive action of various risk factors, and holistic nursing under a social medical model can improve the psychology of patients, improve their self-nursing ability and quality of life.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...