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1.
Curr Microbiol ; 79(11): 325, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125608

RESUMO

The objective of this study is to elucidate the basic biological properties and function of TC0668 in vitro. Laser confocal microscopy and immune-electron microscopy were used to detect localization of TC0668 in Chlamydia-infected human epithelial cells, while the expression phase was investigated by qRT-PCR and western blot analysis. Protein array technology was employed to evaluate differences in cytokine secretion between cells infected with tc0668 single mutants and those infected with tc0668 null mutants. We found that TC0668 is restricted to the chlamydial inclusion. Translation and transcription of TC0668 were detected at 4 h and peaked at 16 h during the life cycle of Chlamydia in vitro. The cytokines produced by tc0668 single mutant infected cultures compared with tc0668 null mutant group indicated that 36 cytokines were downregulated, while 10 were up-regulated significantly. C. muridarum bearing a single tc0668 gene mutation have decreased urogenital pathogenicity that is explained by the effects of the mutation on the regulation of inflammation-related cytokine secretion.


Assuntos
Infecções por Chlamydia , Chlamydia muridarum , Chlamydia muridarum/fisiologia , Citocinas/metabolismo , Humanos , Inflamação , Mutação
3.
J Exp Clin Cancer Res ; 41(1): 267, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071480

RESUMO

BACKGROUND: Circular RNA (circRNA) is crucial to the progression of hepatocellular cancer (HCC). In addition, Mitochondrial calcium uniporter regulatory factor 1 (MCUR1) is commonly overexpressed in HCC to increase cellular ATP levels. Due to the highly aggressive characteristics of HCC, it is essential to identify new diagnostic biomarkers and therapeutic targets that may facilitate the diagnosis of HCC and the development of effective anti-HCC treatments. METHODS: A series of in vitro and in vivo experiments were undertaken to investigate the biological importance and underlying mechanisms of circ_0000098 in HCC. RESULTS: The expression of circ_0000098 was higher in HCC tissues compared to paired adjacent tissues. According to the receiver-operating characteristic curves, circ_0000098 functioned as a potential diagnostic tumor marker in HCC. Our experiments indicated that circ_0000098 served as a key oncogenic circRNA to increase HCC cell proliferation and invasion in vitro and HCC progression in vivo. Furthermore, mechanistic investigation demonstrated that by sequestering miR-383 from the 3'-UTR of MCUR1, circ_0000098 positively regulated MCUR1 expression in HCC cells and finally promoted HCC progression. On the other hand, inhibiting circ_0000098 in HCC cells could diminish doxorubicin (DOX) resistance by decreasing P-glycoprotein (P-gp, MDR1) expression and intracellular ATP levels. Either downregulation of MCUR1 or overexpression of miR-383 improved DOX sensitivity in HCC cells. Subsequently, a short hairpin RNA targeting circ_0000098 (referred to as sh-1) and doxorubicin (DOX) were encapsulated into platelets (PLTs), referred to as DOX/sh-1@PLT. Activated DOX/sh-1@PLT through HCC cells resulted in the creation of platelet-derived particles that were capable of delivering the DOX/sh-1 combination into HCC cells and promoting intracellular DOX accumulation. Furthermore, our in vivo experiments showed that DOX/sh-1@PLT can effectively reduce P-gp expression, promote DOX accumulation, and reverse DOX resistance. CONCLUSIONS: Our results demonstrated that circ_0000098 is an oncogenic circRNA that promotes HCC development through the miR-383/MCUR1 axis and targeting circ_0000098 with DOX/sh-1@PLT may be a promising and practical therapeutic strategy for preventing DOX resistance in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Trifosfato de Adenosina , Carcinogênese/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/genética , Doxorrubicina/farmacologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética
4.
Environ Int ; 169: 107512, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36108500

RESUMO

Paraquat (PQ) is the most widely used herbicide in the world and a well-known potent neurotoxin for humans. PQ exposure has been linked to increase the risk of Parkinson's disease (PD). However, the mechanism underlying its neurotoxic effects in PD pathogenesis is unclear. In our present study, C57BL/6J mice treated with PQ manifested severe motor deficits indicated by the significant reductions in suspension score, latency to fall from rotarod, and grip strength at 8 weeks after PQ exposure. Pathological hallmarks of Parkinsonism in the midbrain such as dopaminergic neuron loss, increased α-synuclein protein, and dysregulated PD-related genes were observed. Non-targeted lipidome analysis demonstrated that PQ exposure alters lipid profile and abundance, increases pro-inflammatory lipids.27 significantly altered subclasses of lipids belonged to 6 different lipid categories. Glycerophospholipids, sphingolipids, and glycerides were the most abundant lipids. Abundance of pro-inflammatory lipids such as Cer, LPC, LPS, and LPI was significantly increased in the midbrain. mRNA expressions of genes regulating ceramide biosynthesis in the midbrain were markedly up-regulated. Moreover, PQ exposure increased serum pro-inflammatory cytokines and provoked neuroinflammation in the midbrain. Pro-inflammatory lipids and cytokines in the midbrain were positively correlated with motor deficits. PQ poisoning in humans significantly also elevated serum pro-inflammatory cytokines and induced an intense systemic inflammation. In summary, we presented initial investigations of PQ induced molecular events related to the PD pathogenesis, capturing aspects of disturbed lipid metabolism, neuroinflammation, impairment of dopaminergic neurons in the midbrain, and an intense systemic inflammation. These neurotoxic effects of PQ exposure may mechanistically contribute to the pathogenesis of PQ induced Parkinsonism. Results of this study also strongly support the hypothesis that ever-increasing prevalence of Parkinson's disease is etiologically linked to the health risk of exposure to neurotoxic environmental pollutants.

5.
Front Cardiovasc Med ; 9: 898289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966552

RESUMO

Background: Pulmonary atresia (PA) is a heterogeneous congenital heart defect and ventricular septal defect (VSD) is the most vital factor for the conventional classification of PA patients. The simple dichotomy could not fully describe the cardiac morphologies and pathophysiology in such a complex disease. We utilized the Human Phenotype Ontology (HPO) database to explore the phenotypic patterns of PA and the phenotypic influence on prognosis. Methods: We recruited 786 patients with diagnoses of PA between 2008 and 2016 at Fuwai Hospital. According to cardiovascular phenotypes of patients, we retrieved 52 HPO terms for further analyses. The patients were classified into three clusters based on unsupervised hierarchical clustering. We used Kaplan-Meier curves to estimate survival, the log-rank test to compare survival between clusters, and univariate and multivariate Cox proportional hazards regression modeling to investigate potential risk factors. Results: According to HPO term distribution, we observed significant differences of morphological abnormalities in 3 clusters. We defined cluster 1 as being associated with Tetralogy of Fallot (TOF), VSD, right ventricular hypertrophy (RVH), and aortopulmonary collateral arteries (ACA). ACA was not included in the cluster classification because it was not an HPO term. Cluster 2 was associated with hypoplastic right heart (HRH), atrial septal defect (ASD) and tricuspid disease as the main morphological abnormalities. Cluster 3 presented higher frequency of single ventricle (SV), dextrocardia, and common atrium (CA). The mortality rate in cluster 1 was significantly lower than the rates in cluster 2 and 3 (p = 0.04). Multivariable analysis revealed that abnormal atrioventricular connection (AAC, p = 0.011) and persistent left superior vena cava (LSVC, p = 0.003) were associated with an increased risk of mortality. Conclusions: Our study reported a large cohort with clinical phenotypic, surgical strategy and long time follow-up. In addition, we provided a precise classification and successfully risk stratification for patients with PA.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35961607

RESUMO

Congenital heart disease (CHD) is one of themost common causes of major birth defects, with a prevalence of 1%. Although an increasing number of studies reported the etiology of CHD, the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice. We therefore developed CHDbase, an evidence-based knowledgebase of CHD-related genes and clinical manifestations manually curated from 1114 publications, linking 1124susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes. Metadata such as the information of each publication and the selected population and samples, the strategy of studies, and the major findings of studies were integrated with each item of the research record. We also integrated functional annotations through parsing ∼50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity. We further prioritized the significance of these CHD-related genes with a gene interaction network approach and extracted a core CHD sub-network with 163 genes. The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin. Overall, CHDbase provides a comprehensive and freely available resource to study CHD susceptibility, supporting a wide range of users in the scientific and medical communities. CHDbase is accessible at http://chddb.fwgenetics.org.

7.
ACS Appl Mater Interfaces ; 14(35): 40126-40135, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36000928

RESUMO

Transition metal thiophosphate, CuInP2S6 (CIPS), has recently emerged as a potentially promising material for photoelectrochemical (PEC) water splitting due to its intrinsic ferroelectric polarization for spontaneous photocarrier separation. However, the poor kinetics of the hydrogen evolution reaction (HER) greatly limits its practical applications. Herein, we report self-enhancing photocatalytic behavior of a CIPS photocathode due to chemically driven oxygen incorporation by photoassisted acid oxidation. The optimal oxygen-doped CIPS demonstrates a >1 order of magnitude enhancement in the photocurrent density compared to that of pristine CIPS. Through comprehensive spectroscopic and microscopic investigations combined with theoretical calculations, we disclose that oxygen doping will lower the Fermi level position and decrease the HER barrier, which further accelerates charge separation and improves the HER activity. This work may deliver a universal and facile strategy for improving the PEC performance of other van der Waals metal thiophosphates.

8.
Comput Math Methods Med ; 2022: 9788122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979048

RESUMO

Objective: To study the effect of positive psychological intervention based on PERMA model on perioperative AIDS patients complicated with breast cancer. Methods: A total of 120 perioperative patients with AIDS complicated with breast cancer treated in our hospital from January 2021 to December 2021 were randomly divided into research group (n = 60) and control group (n = 60). The research group received positive psychological intervention based on PERMA model, while the control group received routine nursing. The scores of disease uncertainty scale (MUIS), Frankl treatment compliance scale, cancer-related fatigue scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS), and quality of life scale EORTCQLQ-C30 (v3.0) were studied. Results: After 12-week nursing, the MUIS score of the research group was lower than that of the control group, and the difference was statistically significant (P < 0.05). After 12 weeks of nursing, the score of Frankl treatment compliance scale in the research group was higher than that in the control group, and the difference was statistically significant (P < 0.05). Following 12-week nursing, the scores of SAS and SDS in the research group were lower than those in the control group, and the difference was statistically significant (P < 0.05). After 12 weeks of nursing, the score of cancer-related fatigue scale in the research group was lower than that in the control group, and the difference was statistically significant (P < 0.05). The EORTCQLQ-C30 (v3.0) scale-symptom domain score in the research group was lower than that in the control group following 12-week nursing, and the difference was statistically significant (P < 0.05). After 12 weeks of nursing, the EORTCQLQ-C30 (v3.0) scale-overall health domain score and functional domain score in the research group were higher than those in the control group, and the difference was statistically significant (P < 0.05). Conclusion: The application value of positive psychological intervention based on PERMA model in perioperative patients with AIDS complicated with breast cancer is more significant. It contributes more to treatment compliance and improves negative feelings of anxiety and depression.


Assuntos
Síndrome de Imunodeficiência Adquirida , Neoplasias da Mama , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Fadiga/etiologia , Fadiga/terapia , Feminino , Humanos , Intervenção Psicossocial , Qualidade de Vida
9.
Artigo em Inglês | MEDLINE | ID: mdl-36016675

RESUMO

Objective: To explore the molecular mechanism of the Cinnamomi ramulus and Paris polyphylla Sm. (C-P) drug pair in the treatment of adenomyosis (AM) based on network pharmacology and animal experiments. Methods: Via a network pharmacology strategy, a drug-component-target-disease network (D-C-T-D) and protein-protein interaction (PPI) network were constructed to explore the core components and key targets of C-P drug pair therapy for AM, and the core components and key targets were verified by molecular docking. Based on the results of network pharmacology, animal experiments were performed for further verification. The therapeutic effect of the C-P drug pair on uterine ectopic lesions was evaluated in a constructed AM rat model. Results: A total of 30 components and 45 corresponding targets of C-P in the treatment of AM were obtained through network pharmacology. In the D-C-T-D network and PPI network, 5 core components and 10 key targets were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the PI3K signaling pathway was the most significantly enriched nontumor pathway. Molecular docking showed that most of the core components and key targets docked completely. Animal experiments showed that the C-P drug pair significantly ameliorated the pathological changes of endometriotic lesions in AM model rats and inhibited PI3K and Akt gene expression, and PI3K and Akt protein phosphorylation. In addition, treatment with the C-P drug pair promoted AM cell apoptosis; upregulated the protein expression of Bax, Caspase-3, and cleaved Caspase-9; and restrained Bcl-2 expression. Conclusions: We propose that the pharmacological mechanism of the C-P drug pair in the treatment of AM is related to inhibition of the PI3K/Akt pathway and promotion of apoptosis in AM ectopic lesions.

10.
Sci Total Environ ; 849: 157819, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35931150

RESUMO

Cadmium (Cd) is a widely distributed endocrine disruptor and has been reported to be closely correlated to the pathogenesis of diabetes. Since pancreatic ß-cells loss and dysfunction are central to pathogenesis of diabetes, studying Cd toxicity on pancreatic ß-cells and its molecular mechanism is an important scientific issue. However, less attention has been payed to study how Cd induces pancreatic ß-cells death and dysfunction in recent years. Thus, our study aims to explore the toxic mechanism of Cd treatment on pancreatic ß-cells using both cellular and animal models. Firstly, it was confirmed that Cd induced decreased cell viability and insulin secretion in a dose-and time-dependent manner in MIN6 cells. To explore the underlying mechanism, transcriptomic analysis was employed to screen the differentially expressed genes and disturbed metabolic pathways. Go and KEGG analysis showed that Cd exposure triggered ferroptosis process in MIN6 cells. We further validated that Cd led to GSH depletion, Gpx4 reduction, lipid peroxidation, mitochondrial membrane potential loss and ultrastructural damage at mitochondrial level. Since immune system process was also perturbed based on GO analysis, we found that Cd activated Ager/Pkc/p65 inflammatory process. Moreover, ferroptosis inhibitor Fer-1 could effectively antagonized the activation of Ager-mediated immune process. It was also revealed that Cd induced iron accumulation as well as decreased Gpx4 expression in mice islets. We also uncovered that Cd led to systemic and pancreatic inflammation as early as third week after Cd exposure. Our study emphasizes the importance of ferroptotic cell death on Cd-induced systemic chronic inflammation. A novel target is provided to prevent Cd-induced pancreatic ß-cells dysfunction and improve the chronic inflammatory state for prediabetes prevention.

11.
Cell Biol Int ; 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36041213

RESUMO

Reprimo (RPRM), a target gene of p53, is a known tumor suppressor. DNA damage induces RPRM, which triggers p53-dependent G2 arrest by inhibiting cyclin B1/Cdc2 complex activation and promotes DNA damage-induced apoptosis. RPRM negatively regulates ataxia-telangiectasia mutated by promoting its nuclear-cytoplasmic translocation and degradation, thus inhibiting DNA damage. Therefore, RPRM plays a crucial role in DNA damage response. Moreover, the loss of RPRM confers radioresistance in mice, which enables longer survival and less severe intestinal injury after radiation exposure. However, the role of RPRM in radiation-induced hematopoietic system injury remains unknown. Herein, utilizing a RPRM-knockout mouse model, we found that RPRM deletion did not affect steady-state hematopoiesis in mice. However, RPRM knockout significantly alleviated radiation-induced hematopoietic system injury and preserved mouse hematopoietic regeneration in hematopoietic stem cells (HSCs) against radiation-induced DNA damage. Further mechanistic studies showed that RPRM loss significantly increased EGFR expression and phosphorylation in HSCs to activate STAT3 and DNA-PKcs, thus promoting HSC DNA repair and proliferation. These findings reveal the critical role of RPRM in radiation-induced hematopoietic system injury, confirming our hypothesis that RPRM may serve as a novel target for radiation protection.

12.
Front Cell Infect Microbiol ; 12: 940906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873170

RESUMO

Foot-and-mouth disease virus (FMDV) could cause acute infection in host cells, or they could coexist with host cells to generate persistent infection. In persistent infection, the virus could survive for a long time in the host and could be transmitted between different host cells. In the case of FMDV-persistent infection cell line, there is a remarkable significant cellular heterogeneity in the FMDV-persistent infection cell line due to differences of viral load in the individual cells within the cell line. However, the mechanisms of FMDV-persistent infection are not well understood. It is now generally accepted that multiple factors contribute to the coevolution of viruses and cells during the course of persistent infection. The outcome would influence the development of persistent FMDV infection conjointly, reaching a state of equilibrium ultimately. Therefore, in order to elucidate the mechanism of cellular heterogeneity in FMDV-persistent infection cell line, single-cell sequencing was performed on BHK-Op, and pseudotime trajectory plot was draw through cell cluster. Based on the cell clusters, we predicted the development and progression of the FMDV-persistent infection. It could be well explained by the fact that, in BHK-Op cells, there are a fraction of infected cells and a fraction of virus-exposed but uninfected bystander cells. By further comparing the transcripts in cell clusters, we found that these genes were involved in changes in ribosome biogenesis, cell cycle, and intracellular signaling including the interferon signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Through comprehensive cross-tabulation analysis of differential expressed genes in various cluster of cells, we identified a high association of Fos, a downstream transcription factor of the MAPK/extracellular signal-regulated kinase (ERK) signaling pathway, with viral replication during the formation of FMDV-persistent infection. Through the further study of Fos, we found that downregulation of Fos facilitates viral clearance during FMDV-persistent infection. Upregulation of c-Raf, which is the upstream of the MAPK/ERK signaling pathway, could promote FMDV replication through downregulation of Fos. Our research is the first to provide insight into the mechanism of the formation FMDV-persistent infection through single-cell sequencing using persistent infection cell line. Pseudotime trajectory analysis was the first time to apply for FMDV-persistent infection cell line. Our work highlights the detailed overview of the evolution of FMDV-persistent infection. We also analyzed the differential expressed genes in the replication or elimination of FMDV within the host. We found that the MAPK/ERK signaling pathway and its downstream transcription factor Fos play an important role in FMDV-persistent infection.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Febre Aftosa/genética , Vírus da Febre Aftosa/genética , Infecção Persistente , Fatores de Transcrição/metabolismo , Replicação Viral/genética
13.
Chemosphere ; 306: 135525, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35779682

RESUMO

Substituted polycyclic aromatic hydrocarbons (SPAHs) are being intensively investigated, considering their high toxicity. Additionally, the mechanism of the effect of substituents on the removal of SPAHs and the activation of Ce(III) ions on peroxymonosulfate (PMS) have not been explored. Here we evaluated the removal efficiency of SPAHs in the oxidation system constructed by Ce(Ⅲ) ions and PMS, with emphasized the effect of substituents on SPAHs degradation. Ce(Ⅲ) has high catalytic performance for PMS, and the degradation percentage of all pollutants was higher than 92%. The significantly negative correlation between the reaction rate constants of SPAHs and the highest occupied molecular orbital-the lowest unoccupied molecular orbital gap, confirms that substituents lead to the differences in the degradation of SPAHs. The generation of reactive oxygen species (SO4•-, •OH, and 1O2) is based on the electron transfer between Ce(Ⅲ) and PMS, and the contribution of ROS to substituted naphthalene varies due to the role of substituents. The Ce(Ⅳ)/Ce(Ⅲ) cycle accelerates the activation of PMS. Based on the transformation products and condensed Fukui function, the possible degradation pathways are inferred. In addition, inorganic anions and organic matter have little effect on the Ce(Ⅲ)/PMS system, which is a prerequisite for applying this system to real-world waste-water for SPAHs removal. This work demonstrates a new model of the degradation mechanism of SPAHs in the Ce(Ⅲ)/PMS system.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , Peróxidos , Hidrocarbonetos Policíclicos Aromáticos/análise , Águas Residuárias , Poluentes Químicos da Água/análise
14.
Front Oncol ; 12: 869253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35875092

RESUMO

Background: To improve the preoperative diagnostic accuracy and reduce the non-therapeutic thymectomy rate, we established a comprehensive predictive nomogram based on radiomics data and computed tomography (CT) features and further explored its potential use in clinical decision-making for anterior mediastinal masses (AMMs). Methods: A total of 280 patients, including 280 with unenhanced CT (UECT) and 241 with contrast-enhanced CT (CECT) scans, all of whom had undergone thymectomy for AMM with confirmed histopathology, were enrolled in this study. A total of 1,288 radiomics features were extracted from each labeled mass. The least absolute shrinkage and selection operator model was used to select the optimal radiomics features in the training set to construct the radscore. Multivariate logistic regression analysis was conducted to establish a combined clinical radiographic radscore model, and an individualized prediction nomogram was developed. Results: In the UECT dataset, radscore and the UECT ratio were selected for the nomogram. The combined model achieved higher accuracy (AUC: 0.870) than the clinical model (AUC: 0.752) for the prediction of therapeutic thymectomy probability. In the CECT dataset, the clinical and combined models achieved higher accuracy (AUC: 0.851 and 0.836, respectively) than the radscore model (AUC: 0.618) for the prediction of therapeutic thymectomy probability. Conclusions: In patients who underwent UECT only, a nomogram integrating the radscore and the UECT ratio achieved good accuracy in predicting therapeutic thymectomy in AMMs. However, the use of radiomics in patients with CECT scans did not improve prediction performance; therefore, a clinical model is recommended.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35873631

RESUMO

Objective: To clarify the mechanism of icariin (ICA) promoting gastric cancer (GC) cell apoptosis by regulating circ_0003159/eIF4A3/bcl-2 axis. Methods: The mRNA or protein levels were detected by qRT-PCR or the western blot. The interaction between eIF4A3 protein and circ_0003159 or eIF4A3 protein and bcl-2 mRNA were validated by RNA pull down assays and the RNA immunoprecipitation (RIP) assay. The cell viability was measured by the cell counting kit (CCK)-8 kit. The cell apoptosis was measured by flow cytometry. Results: Compared with the group Vector, the ratio of cytoplasmic eIF4A3/nuclear eIF4A3 in the cell with circ_0003159 overexpression was significantly higher. RIP and RNA pull down results proved the interaction between eIF4A3 and circ_0003159. The RIP assay further validated the interaction between eIF4A3 and bcl-2. By gain or loss of the functional experiment, hsa_circ_0003159 was proved to recruit eIF4A3 to inhibit bcl-2 expression. Hsa_circ_0003159 regulates eIF4A3/bcl-2 to reduce GC cell viability and increase apoptosis Furthermore, ICA regulates hsa_circ_0003159/eIF4A3/bcl-2 axis to inhibit GC cell activity and induce GC cell apoptosis in vitro. Conclusion: These data showed that ICA could effectively reduce the GC cell activity and induce GC cell apoptosis via hsa_circ_0003159/eIF4A3/bcl-2 axis, which provides new theoretical evidence for the treatment of GC by ICA.

16.
J Gastrointest Surg ; 26(9): 1917-1929, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35689008

RESUMO

PURPOSE: The number of neuroendocrine tumors (NETs) is gradually increasing worldwide, and those located in the small intestine (siNETs) are the most common. As some biological and clinical characteristics of tumors of the jejunum and the ileum differ, there is a need to assess the prognosis of individuals with siNETs of the jejunum and ileum separately. We generated a predictive nomogram by assessing individuals with siNETs from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We used univariate Cox regression analysis to determine both the overall survival (OS) and the cancer-specific survival (CSS) of 2501 patients with a pathological confirmation of siNETs of the jejunum and ileum. To predict 3-, 5-, and 10-year OS of siNETs, a nomogram was generated based on a training cohort and validated with an external cohort. Accuracy and clinical practicability were evaluated separately by Harrell's C-indices, calibration plots, and decision curves. The correlation was examined between dissected lymph nodes and positive lymph nodes. RESULTS: Dissection of 7 or more lymph nodes significantly improved patient OS and was found to be a protective factor for patients with siNETs. In Cox regression analyses, age, primary site, tumor size, N stage, M stage, and regional lymph node examination were significant predictors in the nomogram. A significant positive correlation was found between dissected lymph nodes and positive lymph nodes. CONCLUSIONS: Patients with 7 or more dissected lymph nodes showed an accurate tumor stage and a better prognosis. Our nomogram accurately predicted the OS of patients with siNETs.


Assuntos
Tumores Neuroendócrinos , Humanos , Íleo/patologia , Jejuno/patologia , Linfonodos/patologia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Nomogramas , Prognóstico , Programa de SEER
17.
Materials (Basel) ; 15(12)2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35744220

RESUMO

Compared to magnetorheological fluid, magnetorheological gel has better anti-settling performance and stability. Therefore, magnetorheological gel is suitable for devices that can meet operational requirements in all aspects after long-term storage, such as the anti-recoil application of weapons. To study this in-depth, the mechanism of the influence of magnetorheological gel micro-magnetic-mechanical properties on the macro-output damping mechanics of the damper, a parallel plate model of the mixed flow mode composed of Couette shear flow and Poiseuille pressure flow was established. The theoretical analysis was of the output damping of the damper. Finally, the controllability of the damper under impact load employed magnetorheological gel was preliminarily analyzed. The results indicate that the damping coefficient of the damper increases with the increase of dynamic viscosity ηB of the magnetorheological gel, piston effective cross-sectional area AP, magnetic pole L, and Bingham coefficient Bi. Magnetorheological damper has controllability under impact load and can reach a wide controllable range under the condition under small magnetic field ranging from 0 mT to 131 mT.

18.
Biomed Pharmacother ; 153: 113326, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35759865

RESUMO

Heart failure with preserved ejection fraction (HFpEF) reduces the quality of life, costs substantial medical resources, and has a high mortality. However, we lack an effective therapy for HFpEF due to our limited knowledge of its mechanism. Therefore, it is crucial to explore novel therapeutics, such as those with endogenous protective roles, and seek new targeted therapies. Epoxyeicosatrienoic acids (EETs) are endogenous bioactive metabolites of arachidonic acids produced by cytochrome P450 (CYP) epoxygenases. EETs can function as endogenous cardioprotective factors with potent inhibitory roles in inflammation, endothelial dysfunction, cardiac remodeling, and fibrosis, which are the fundamental mechanisms of HFpEF. This suggests that EETs have the potential function to protect against HFpEF. Therefore, we present an overview of the ever-expanding world of EETs and how they might help alleviate the pathophysiology underlying HFpEF to provide new insights for research in this field.


Assuntos
Insuficiência Cardíaca , Humanos , Inflamação , Qualidade de Vida , Volume Sistólico/fisiologia , Função Ventricular Esquerda
19.
Cell Discov ; 8(1): 58, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35725971

RESUMO

Cancer-associated lymphedema frequently occurs following lymph node resection for cancer treatment. However, we still lack effective targeted medical therapies for the treatment or prevention of this complication. An in-depth elucidation of the cellular alterations in subcutaneous adipose tissues of lymphedema is essential for medical development. We performed single-cell RNA sequencing of 70,209 cells of the stromal vascular fraction of adipose tissues from lymphedema patients and healthy donors. Four subpopulations of adipose-derived stromal cells (ASCs) were identified. Among them, the PRG4+/CLEC3B+ ASC subpopulation c3 was significantly expanded in lymphedema and related to adipose tissue fibrosis. Knockdown of CLEC3B in vitro could significantly attenuate the fibrogenesis of ASCs from patients. Adipose tissues of lymphedema displayed a striking depletion of LYVE+ anti-inflammatory macrophages and exhibited a pro-inflammatory microenvironment. Pharmacological blockage of Trem1, an immune receptor predominantly expressed by the pro-inflammatory macrophages, using murine LR12, a dodecapeptide, could significantly alleviate lymphedema in a mouse tail model. Cell-cell communication analysis uncovered a perivascular ligand-receptor interaction module among ASCs, macrophages, and vascular endothelial cells. We provided a comprehensive analysis of the lineage-specific changes in the adipose tissues from lymphedema patients at a single-cell resolution. CLEC3B was found to be a potential target for alleviating adipose tissue fibrosis. Pharmacological blockage of TREM1 using LR12 could serve as a promising medical therapy for treating lymphedema.

20.
Plants (Basel) ; 11(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35684181

RESUMO

The development of rootstocks with a high-quality dwarf-type root system is a popular research topic in the apple industry. However, the precise breeding of rootstocks is still challenging, mainly because the root system is buried deep underground, roots have a complex life cycle, and research on root architecture has progressed slowly. This paper describes ideas for the precise breeding and domestication of wild apple resources and the application of key genes. The primary goal of this research is to combine the existing rootstock resources with molecular breeding and summarize the methods of precision breeding. Here, we reviewed the existing rootstock germplasm, high-quality genome, and genetic resources available to explain how wild resources might be used in modern breeding. In particular, we proposed the 'from genotype to phenotype' theory and summarized the difficulties in future breeding processes. Lastly, the genetics governing root diversity and associated regulatory mechanisms were elaborated on to optimize the precise breeding of rootstocks.

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