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1.
J Mater Chem B ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34308944

RESUMO

The hyperglycemic environment and the presence of bacterial infections delay the healing of diabetic wounds. Herein, glucose oxidase (GOx) and Fe3O4/TiO2/Ag3PO4 were embedded in a polyacrylic acid-calcium phosphate (PAA-CaPs@Nps@GOx) hydrogel through an in situ biomimetic mineralization approach. The GOx encapsulation efficiency was 96.75% and exhibited exceptional enzyme activity stability. Moreover, the co-immobilization of GOx and Fe3O4/TiO2/Ag3PO4 nanoparticles generated a simple and multifunctional antibacterial platform with the advantages of decreasing blood glucose concentration and efficiently producing reactive oxygen species (ROS). In addition, the degradation rate of the hydrogel was controlled by regulating the concentration of phosphate thus controlling the release of Fe3O4/TiO2/Ag3PO4 and GOx. As a result, both the potential toxicity and oxidative stress associated with the antimicrobial biomaterial can be controlled within the body therefore potentially preventing detriment. In vivo results indicated that the PAA-CaPs@Nps@GOx hydrogel effectively promoted diabetic wound healing and showed great potential for clinical applications of chronic wound management.

2.
Pest Manag Sci ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34310017

RESUMO

BACKGROUND: Tomato chlorosis virus (ToCV) is mainly vectored by Bemisia tabaci (B. tabaci) in China, which has a worldwide distribution, and greatly reduces the yields of tomato and other vegetables. At present, control of ToCV has been focused mainly by the use of insecticides to control whitefly populations. Transcriptome sequencing showed high expression of the B. tabaci Bta11975 gene, an α-glucosidase (AGLU) during ToCV acquisition by whitefly Mediterranean (MED) species. To investigate the role of Bta11975 gene in ToCV acquisition and transmission by B. tabaci MED, we used RNA interference (RNAi) to reduce the expression of Bta11975 gene. RESULTS: The relative expression of Bta11975 gene was correlated with the ToCV content in B. tabaci. AGLU is highly expressed in primary salivary gland and gut. After Bta11975 gene was silenced, the gene expression of B. tabaci was reduced and B. tabaci mortality was increased. Besides, ToCV acquisition by B. tabaci at 48 and 72-h acquisition access period was reduced, and ToCV transmission was significantly reduced by 25 or 50 of B. tabaci. CONCLUSIONS: These results indicate that suppression of expression of the Bta11975 gene in B. tabaci MED by RNA interference can reduce acquisition and transmission of ToCV by B. tabaci MED. This article is protected by copyright. All rights reserved.

3.
J Cell Mol Med ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34258872

RESUMO

Clinical studies have shown that dapagliflozin can reduce cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM), but the exact mechanism is unclear. In this study, we used the molecular docking and network pharmacology methods to explore the potential mechanism of dapagliflozin on T2DM complicated with cardiovascular diseases (CVD). Dapagliflozin's potential targets were predicted via the Swiss Target Prediction platform. The pathogenic targets of T2DM and CVD were screened by the Online Mendelian Inheritance in Man (OMIM) and Gene Cards databases. The common targets of dapagliflozin, T2DM and CVD were used to establish a protein-protein interaction (PPI) network; the potential protein functional modules in the PPI network were found out by MCODE. Metascape tool was used for Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A potential protein functional module with the best score was obtained from the PPI network and 9 targets in the protein functional module all showed good binding properties when docking with dapagliflozin. The results of KEGG pathway enrichment analysis showed that the underlying mechanism mainly involved AGE-RAGE signalling pathway in diabetic complications, TNF signalling pathway and MAPK signalling pathway. Significantly, the MAPK signalling pathway was considered as the key pathway. In conclusion, we speculated that dapagliflozin played a therapeutic role in T2DM complicated with CVD mainly through MAPK signalling pathway. This study preliminarily reveals the possible mechanism of dapagliflozin in the treatment of T2DM complicated with CVD and provides a theoretical basis for future clinical research.

4.
Biomed Res Int ; 2021: 8848227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34250091

RESUMO

Objective: Autophagy and long noncoding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma. Methods: We downloaded RNA sequencing data and clinical information of melanoma from the Cancer Genome Atlas. The coexpression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate Cox regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups. Results: According to the results of the univariate Cox analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate Cox analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p < 0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism. Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNA risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34254770

RESUMO

Organic-inorganic metal halide perovskite materials have been widely studied as the light absorber for efficient photovoltaics. However, perovskite layers with defective nature are typically prepared with an uncontrollable crystallization process, intrinsically limiting further advance in device performance, and thus require delicate manipulation of crystallization processes and defect density. Here, we demonstrate an ammonium-assisted crystallization of perovskite absorbers during a two-step deposition to fabricate efficient solar cells. Addition of ammonium iodide (NH4I) is devised to manipulate the nucleation and crystal growth of perovskite, wherein the formation and transition of intermediate x[NH4+]•[PbI3]x- enables high-quality perovskite layers with an enlarged grain and reduced defect density. As a result, the perovskite solar cells (PSCs) achieve an average efficiency of 21.36% with a champion efficiency of 22.15% and improved environmental stability over 30 days in ambient conditions with varied relative humidity. These results with addition of NH4I provide an available and ingenious way to construct high-quality perovskite layers for efficient solar cells and will advance the commercial application of perovskite-based photovoltaics.

6.
J Org Chem ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264081

RESUMO

Nickel-catalyzed asymmetric hydrogenation for kinetic resolution of [2.2]paracyclophane-derived cyclic N-sulfonylimines was successfully developed. High selectivity factors were observed in most cases (s up to 89), providing the recovered materials and hydrogenation products in good yields with high levels of enantiopurity. The recovered materials and hydrogenation products are useful synthetic intermediates for the synthesis of planar chiral [2.2]paracyclophane-based compounds.

7.
Hepatology ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34297426

RESUMO

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is currently one of the most common causes of liver transplantation and hepatocellular carcinoma. Thus far, there is still no effective pharmacological therapy for this disease. Recently, Gastrodin has demonstrated hepatoprotective effects in a variety of liver diseases. The aim of this study is to investigate the function of Gastrodin in NASH. APPROACH AND RESULT: In our study, Gastrodin showed potent therapeutic effects on NASH both in vivo and in vitro. In high-fat diet (HFD)- or high-fat and high-cholesterol (HFHC) diet-fed mice, the liver weight, hepatic and serum triglyceride and cholesterol contents, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity levels were markedly reduced by Gastrodin treatment as compared to the corresponding vehicle groups. Notably, Gastrodin showed minimal effects on the function and histological characteristics of other major organs in mice. We further examined the effects of Gastrodin on lipid accumulation in primary mouse hepatocytes and human hepatocyte cell line, and observed that Gastrodin showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. Furthermore, RNA-Seq analysis systemically indicated that Gastrodin suppressed the pathway and key regulators related to lipid accumulation, inflammation and fibrosis in the pathogenesis of NASH. Mechanistically, we found that Gastrodin protected against NASH by activating the AMPK pathway, which was supported by the result that the AMPK inhibitor compound C or AMPK knockdown blocked the Gastrodin-mediated hepatoprotective effect. CONCLUSION: Gastrodin attenuates steatohepatitis by activating the AMPK pathway and represents a novel therapeutic for the treatment of NASH.

8.
J Bone Miner Metab ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212247

RESUMO

INTRODUCTION: Bone loss is a major health concern for astronauts during long-term spaceflight and for patients during prolonged bed rest or paralysis. It is essential to develop therapeutic strategies to combat the bone loss occurring in people afflicted with disuse atrophy on earth as well as in astronauts in space, especially during prolonged missions. Although several drugs have been demonstrated for treating postmenopausal osteoporosis or bone-related diseases, their effects on microgravity-induced bone loss are still unclear. MATERIALS AND METHODS: Here, we employed the hindlimb-unloading (HLU) tail suspension model and compared the preventive efficiencies of five agents including alendronate (ALN), raloxifene (Rox), teriparatide (TPTD), anti-murine RANKL monoclonal antibody (anti-RANKL) and proteasome inhibitor bortezomib (Bzb) on mechanical unloading-induced bone loss. Bone mineral density (BMD) was measured by quantitative computed tomography. The osteoblastic and osteoclastic activity were measured by serum ELISA, histology analysis, and histomorphometric analysis. RESULTS: Compared to the control, ALN and anti-RANKL antibody could restore bone mass close to sham levels by inhibiting bone resorption. Bzb could increase the whole bone mass and strength by inhibiting bone resorption and promoting bone formation simultaneously. Meanwhile, Rox did not affect bone loss caused by HLU. TPTD stimulated cortical bone formation but the total bone mass was not increased significantly. CONCLUSIONS: We demonstrated for the first time that anti-RANKL antibody and Bzb had a positive effect on preventing mechanical unloading-induced bone loss. This finding puts forward the potential use of anti-RANKL and Bzb on bone loss therapies or prophylaxis of astronauts in spaceflight.

9.
Cell Res ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267350
10.
J Hazard Mater ; 419: 126454, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34198221

RESUMO

Nanoplastics (NPs) cause various adverse effects on marine fish. However, effects of dietary NPs exposure on liver lipid metabolism and muscle nutritional quality of carnivorous marine fish are not fully understood. In this study, a 21-day feeding test was conducted to simulate the food chain transfer of polystyrene nanoplastics (PS NPs) and then evaluate effects of different dietary PS NPs levels on the survival, growth performance, liver lipid metabolism, and muscle nutritional quality of large yellow croaker Larimichthys crocea. Results indicated that the survival and growth of large yellow croaker decreased with the increase of PS NPs levels. Moreover, PS NPs induced excessive liver lipid accumulation by down-regulating the expression of lipolysis-related genes and inhibiting the AMPK-PPARα signaling pathway. In vitro, PS NPs could be accumulated in hepatocytes, reduce cell viability, and disrupt lipid metabolism of hepatocytes. Also, we found for the first time that PS NPs altered fatty acid composition and texture of fish muscle by enhancing oxidative stress and disrupting lipid metabolism. Overall, this study indicated that PS NPs induced liver lipid deposition by inhibiting lipolysis, and demonstrated that PS NPs altered the nutritional quality of fish, which might cause potential health effects for human consumers.

11.
Zhongguo Zhen Jiu ; 41(6): 598-602, 2021 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-34085474

RESUMO

OBJECTIVE: To observe the protective effect of electroacupuncture (EA) at Neiguan (PC 6) on pulmonary function during one-lung ventilation (OLV) in patients with lobectomy, and explore its action mechanism. METHODS: Sixty patients with lobectomy were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the control group were treated with general anesthesia, and OLV was given when surgery began; when the surgery finished, air was removed from the thoracic cavity and two-lung ventilation was performed. On the basis of the treatment in the control group, the patients in the observation group were treated with EA (disperse-dense wave, 2 Hz/100 Hz of frequency) at Neiguan (PC 6) 30 min before anesthesia induction until the end of the surgery. The pulmonary function indexes [arterial partial pressure of oxygen (PaO2), oxygenation index (OI), compliance of lung (CL), respiratory index (RI)] and serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were observed before surgery (T0), 30 min into OLV (T1), 60 min into OLV (T2) and after operation (T3). The total incidence of complications, pressing times of postoperative patient-controlled analgesia pump in 48 h after surgery and hospital stay were compared between the two groups. RESULTS: Compared with T0, the PaO2, OI, CL and serum SOD at T1, T2 and T3 in the two groups were decreased (P<0.05), and those in the observation group were higher than those in the control group (P<0.05). The RI and serum levels of MDA, IL-6, TNF-α at T1, T2 and T3 in the two groups were increased, and those in the observation group were lower than those in the control group (P<0.05). The total incidence of complications in the observation group was lower than that in the control group [3.3% (1/30) vs 23.3% (7/30), P<0.05]. The pressing times of postoperative patient-controlled analgesia pump in 48 h after surgery and hospital stay in the observation group were less than those in the control group (P<0.05). CONCLUSION: EA at Neiguan (PC 6) has protective effects on lung injury induced by OLV after lobectomy, and its mechanism may be related to the improvement of oxidative stress and inflammatory response.


Assuntos
Eletroacupuntura , Lesão Pulmonar , Ventilação Monopulmonar , Anestesia Geral , Humanos , Pulmão
12.
Nat Nanotechnol ; 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083773

RESUMO

Flash memory has become a ubiquitous solid-state memory device widely used in portable digital devices, computers and enterprise applications. The development of the information age has demanded improvements in memory speed and retention performance. Here we demonstrate an ultrafast non-volatile flash memory based on MoS2/hBN/multilayer graphene van der Waals heterostructures, which achieves an ultrafast writing/erasing speed of 20 ns through two-triangle-barrier modified Fowler-Nordheim tunnelling. Using detailed theoretical analysis and experimental verification, we postulate that a suitable barrier height, gate coupling ratio and clean interface are the main reasons for the breakthrough writing/erasing speed of our flash memory devices. Because of its non-volatility this ultrafast flash memory could provide the foundation for the next generation of high-speed non-volatile memory.

13.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070207

RESUMO

In domestic ruminants, endometrial receptivity is related to successful pregnancy and economic efficiency. Despite several molecules having been reported in the past regarding endometrial receptivity regulation, much regarding the mechanism of endometrial receptivity regulation remains unknown due to the complex nature of the trait. In this work, we demonstrated that the cysteine-rich transmembrane bone morphogenetic protein (BMP) regulator 1 (CRIM1) served as a novel regulator in the regulation of goat endometrial receptivity in vitro. Our results showed that hormones and IFN-τ increased the expression of CRIM1 in goat endometrial epithelial cells (EECs). Knockdown of CRIM1 via specific shRNA hindered cell proliferation, cell adhesion and prostaglandins (PGs) secretion and thus derailed normal endometrial receptivity. We further confirmed that receptivity defect phenotypes due to CRIM1 interference were restored by ATG7 overexpression in EECs while a loss of ATG7 further impaired receptivity phenotypes. Moreover, our results showed that changing the expression of ATG7 affected the reactive oxygen species (ROS) production. Moreover, mR-143-5p was shown to be a potential upstream factor of CRIM1-regulated endometrial receptivity in EECs. Overall, these results suggest that CRIM1, as the downstream target of miR-143-5p, has effects on ATG7-dependent autophagy, regulating cell proliferation, cell adhesion and PG secretion, and provides a new target for the diagnosis and treatment of early pregnancy failure and for improving the success rates of artificial reproduction.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas/fisiologia , Implantação do Embrião/genética , Endométrio/fisiologia , Cabras/fisiologia , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Autofagia/fisiologia , Proteína 7 Relacionada à Autofagia/deficiência , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/fisiologia , Receptores de Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Receptores de Proteínas Morfogenéticas Ósseas/genética , Adesão Celular , Proliferação de Células , Células Cultivadas , Implantação do Embrião/fisiologia , Endométrio/citologia , Endométrio/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Estradiol/farmacologia , Feminino , Técnicas de Silenciamento de Genes , Cabras/genética , Interferon Tipo I/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos , Gravidez , Proteínas da Gravidez/farmacologia , Progesterona/farmacologia , Prostaglandinas/metabolismo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima
14.
Mol Oncol ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060699

RESUMO

Ovarian cancer disseminates primarily intraperitoneally. Detached tumor cell aggregates (spheroids) from the primary tumor are regarded as 'metastatic units' that exhibit a low sensitivity to classical chemotherapy, probably due to their unique molecular characteristics. We have analyzed the cellular composition of ascites from OvCa patients, using flow cytometry, and studied their behavior in vitro and in vivo. We conclude that ascites-derived cultured cells from OvCa patients give rise to two subpopulations: adherent cells and non-adherent cells. Here, we found that the AD population includes mainly CD90+ cells with highly proliferative rates in vitro but no tumorigenic potential in vivo, whereas the NAD population contains principally tumor cell spheroids (EpCAM+ /CD24+ ) with low proliferative potential in vitro. Enriched tumor cell spheroids from the ascites of high-grade serous OvCA patients, obtained using cell strainers, were highly tumorigenic in vivo and their metastatic spread pattern precisely resembled the tumor dissemination pattern found in the corresponding patients. Comparative transcriptome analyses from ascites-derived tumor cell spheroids (n = 10) versus tumor samples from different metastatic sites (n = 30) revealed upregulation of genes involved in chemoresistance (TGM1, HSPAs, MT1s), cell adhesion and cell-barrier integrity (PKP3, CLDNs, PPL), and the oxidative phosphorylation process. Mitochondrial markers (mass and membrane potential) showed a reduced mitochondrial function in tumoroids from tumor tissue compared with ascites-derived tumor spheroids in flow cytometry analysis. Interestingly, response to OXPHOS inhibition by metformin and IACS010759 in tumor spheroids correlated with the extent of mitochondrial membrane potential measured by fluorescence-activated cell sorting. Our data contribute to a better understanding of the biology of ovarian cancer spheroids and identify the OXPHOS pathway as new potential treatment option in advanced ovarian cancer.

15.
Addict Behav ; 121: 106993, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34098430

RESUMO

Cross-sectional studies have documented a positive association between academic procrastination and problematic mobile phone use (PMPU). However, the specific predictive direction has remained controversial and the potential mechanisms underlying the association have not been rigorously evaluated. According to Davis's cognitive-behavioral model, Brand et al.'s I-PACE model, and procrastination-related theories, academic procrastination and PMPU might have a reciprocal relationship and distraction cognitions might play a mediating role in this process. A total of 633 secondary school students completed three self-report questionnaires at three 6-month intervals over the course of 1.5 years. The cross-lagged panel model results showed that earlier academic procrastination positively predicted subsequent PMPU over time, but the reverse prediction was not stable. Furthermore, distraction cognitions played a mediating role in linking earlier academic procrastination and subsequent PMPU. These findings indicate that academic procrastination precedes PMPU with distraction cognitions as a potential mediator, which contributes to clarifying the controversial relationship and explicating the underlying mechanism. Overall, interventions for academic procrastination may be effective in reducing maladaptive cognitions associated with mobile phones and preventing adolescents from developing PMPU.


Assuntos
Uso do Telefone Celular , Procrastinação , Adolescente , China/epidemiologia , Cognição , Estudos Transversais , Humanos , Estudantes
16.
Medicine (Baltimore) ; 100(23): e26098, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114994

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is the most common malignant tumor of the hematopoietic system, which seriously threatens the lives of patients. Most AML patients have acute onset, severe condition, and poor prognosis. The present study aimed to comprehensively evaluate the effectiveness and safety of chemotherapy combined with different doses of interleukin-2 (IL-2) maintenance treatments in AML by Bayesian network meta-analysis (NMA). METHODS: From its inception until October 2021, we will search PubMed, Cochrane Library, CNKI, Embase, and other databases to comprehensively collect randomized controlled trials (RCTs) of chemotherapy combined with different doses of IL-2 maintenance therapies for AML. Two independent researchers will complete the literature screening and data extraction according to the inclusion and exclusion criteria, and then independently conduct a bias risk assessment of all the evidence. Bayesian NMA was used to evaluate all the evidence comprehensively. Use STATA16.0 and WinBUGS1.4.3 software to process and analyze all data, and classify the quality of evidence in NMA according to grading of recommendations assessment, development, and evaluation . RESULTS: The study will evaluate the efficacy and safety of chemotherapy combined with different doses of IL-2 maintenance therapies for AML. CONCLUSION: The study will provide a basis for the efficacy and safety of chemotherapy combined with different doses of IL-2 maintenance therapies for AML. We hope that this study can provide meaningful support for clinicians and patients. PROTOCOL REGISTRATION NUMBER: INPLASY202140106. ETHICAL APPROVAL: Since the study is based on published or registered RCTs, ethical approval and patient informed consent are abandoned.


Assuntos
Interleucina-2/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Antineoplásicos/farmacologia , Teorema de Bayes , Humanos , Metanálise em Rede , Projetos de Pesquisa
17.
Artigo em Inglês | MEDLINE | ID: mdl-34170806

RESUMO

BACKGROUND: Esophageal carcinoma (ESCA) is a malignant tumor with high invasiveness and mortality. Autophagy has multiple roles in the development of cancer; however, there are limited data on autophagy genes associated with long non-coding RNAs (lncRNAs) in ESCA. The purpose of this study was to screen potential diagnostic and prognostic molecules and to identify gene co-expression networks associated with autophagy in ESCA. METHODS: We downloaded transcriptome expression profiles from The Cancer Genome Atlas and autophagy-related gene data from the Human Autophagy Database and analyzed the co-expression of mRNAs and lncRNAs. In addition, the diagnostic and prognostic value of autophagy-related lncRNAs was analyzed by multivariate Cox regression. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis was carried out for high-risk patients, and enriched pathways were analyzed by gene set enrichment analysis. RESULTS: The results showed that genes of high-risk patients were enriched in protein export and spliceosome. Based on Cox stepwise regression and survival analysis, we identified seven autophagy-related lncRNAs with prognostic and diagnostic value, with the potential to be used as a combination to predict the prognosis of patients with ESCA. Finally, a co-expression network related to autophagy was constructed. CONCLUSION: These results suggest that autophagy-related lncRNAs and the spliceosome play important parts in the pathogenesis of ESCA. Our findings provide new insight into the molecular mechanism of ESCA and suggest a new method for improving its treatment.

18.
Sci Transl Med ; 13(597)2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108252

RESUMO

Studies have failed to translate more than 1000 experimental treatments from bench to bedside, leaving stroke as the second leading cause of death in the world. Thrombolysis within 4.5 hours is the recommended therapy for stroke and cannot be performed until neuroimaging is used to distinguish ischemic stroke from hemorrhagic stroke. Therefore, finding a common and critical therapeutic target for both ischemic and hemorrhagic stroke is appealing. Here, we report that the expression of myeloid differentiation protein 2 (MD2), which is traditionally regarded to be expressed only in microglia in the normal brain, was markedly increased in cortical neurons after stroke. We synthesized a small peptide, Trans-trans-activating (Tat)-cold-inducible RNA binding protein (Tat-CIRP), which perturbed the function of MD2 and strongly protected neurons against excitotoxic injury in vitro. In addition, systemic administration of Tat-CIRP or genetic deletion of MD2 induced robust neuroprotection against ischemic and hemorrhagic stroke in mice. Tat-CIRP reduced the brain infarct volume and preserved neurological function in rhesus monkeys 30 days after ischemic stroke. Tat-CIRP efficiently crossed the blood-brain barrier and showed a wide therapeutic index for stroke because no toxicity was detected when high doses were administered to the mice. Furthermore, we demonstrated that MD2 elicited neuronal apoptosis and necroptosis via a TLR4-independent, Sam68-related cascade. In summary, Tat-CIRP provides robust neuroprotection against stroke in rodents and gyrencephalic nonhuman primates. Further efforts should be made to translate these findings to treat both ischemic and hemorrhagic stroke in patients.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Humanos , Macaca mulatta , Camundongos , Peptídeos , Roedores , Acidente Vascular Cerebral/tratamento farmacológico
19.
Sex Transm Dis ; 48(8): 550-556, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34110748

RESUMO

BACKGROUND: Young men who have sex with men (YMSM) are particularly at increased risk for human papillomavirus (HPV) infection and related malignancies. Rectal douching, commonly practiced among MSM, has been associated with HIV, chlamydia, gonorrhea, and viral hepatitis in cross-sectional studies. We conducted this study to understand the association between self-reported rectal douching and anal HPV among YMSM in China. METHODS: Between September 2018 and March 2019, MSM aged 15 to 24 years who ever engaged in receptive anal intercourse over the last 3 months were recruited via community-based organizations and centers for disease control located in 4 cities in China. Participants were asked to complete an online survey. We performed multivariate logistic regression adjusted for potential confounders to examine the association between self-reported rectal douching and anal HPV. RESULTS: Among 273 MSM with a median age of 20 years (interquartile range, 19-21 years) included in this study, 130 (47.6%) practiced rectal douching during the preceding 3 months and 96 (36.2%) were infected with anal HPV. Self-reported rectal douching was found to be associated with increased odds of anal HPV infection (odds ratio, 2.16; 95% confidence interval, 1.22-3.82) among YMSM, after adjusting for age, sexual debut, sex with alcohol or drugs, and HIV testing history. CONCLUSIONS: Self-reported rectal douching is associated with higher odds of anal HPV infection independent of sexual behaviors among YMSM. More prospective studies to ascertain this association are needed. Health education materials should inform men of the potential risk of rectal douching. Research on safer rectal douching procedures is warranted.

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