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1.
Environ Res ; : 115359, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36706902

RESUMO

In this study, roasted spent HDS ash (sHDSc-A) was used for the first time to catalytically pyrolyze oily spent HDS catalysts (sHDSc) to improve the yield and quality of pyrolysis oil. The results showed that sHDSc-A promoted the decomposition of coke in oily sHDSc, resulting in the recovery of more oil and gas. Meanwhile, sHDSc-A significantly improved the quality of the pyrolysis oil. They inhibited the aromatization of alkanes to increase the saturation of the pyrolysis oil from 59.39% to 74.25% and the H/C radio from 1.62 to 1.72; promoted the decomposition of long-chain alkanes to increase the content of C11-C22 from 41.97% to 61.99%; enhanced the conversion of carboxylic acids to ketones led to the reduction of heteroatomic compounds such as N (56.10%-45.39%), S (66.95%-56.59%), and O (45.26%-26.70%) in the pyrolysis oil. The promotion of sHDSc-A in the pyrolysis process is attributed to the catalytic effect of the metal oxides in sHDSc-A. Among them, Al2O3 and Fe2O3 can promote decarboxylation of carboxylic acids and reduce O mobility, while MoO3 and Fe2O3 play a significant role in reducing coke and increasing pyrolysis oil. NiO can also promote methane vapor reforming, and thus increase the production of H2 in non-condensable gas. This study achieves self-circulation of oily sHDSc with a "waste-treatment-waste" strategy that presents the advantage of value-added energy recovery and waste reuse.

2.
BMJ Open ; 13(1): e066322, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599634

RESUMO

OBJECTIVES: Medical artificial intelligence (AI) has been used widely applied in clinical field due to its convenience and innovation. However, several policy and regulatory issues such as credibility, sharing of responsibility and ethics have raised concerns in the use of AI. It is therefore necessary to understand the general public's views on medical AI. Here, a meta-synthesis was conducted to analyse and summarise the public's understanding of the application of AI in the healthcare field, to provide recommendations for future use and management of AI in medical practice. DESIGN: This was a meta-synthesis of qualitative studies. METHOD: A search was performed on the following databases to identify studies published in English and Chinese: MEDLINE, CINAHL, Web of science, Cochrane library, Embase, PsycINFO, CNKI, Wanfang and VIP. The search was conducted from database inception to 25 December 2021. The meta-aggregation approach of JBI was used to summarise findings from qualitative studies, focusing on the public's perception of the application of AI in healthcare. RESULTS: Of the 5128 studies screened, 12 met the inclusion criteria, hence were incorporated into analysis. Three synthesised findings were used as the basis of our conclusions, including advantages of medical AI from the public's perspective, ethical and legal concerns about medical AI from the public's perspective, and public suggestions on the application of AI in medical field. CONCLUSION: Results showed that the public acknowledges the unique advantages and convenience of medical AI. Meanwhile, several concerns about the application of medical AI were observed, most of which involve ethical and legal issues. The standard application and reasonable supervision of medical AI is key to ensuring its effective utilisation. Based on the public's perspective, this analysis provides insights and suggestions for health managers on how to implement and apply medical AI smoothly, while ensuring safety in healthcare practice. PROSPERO REGISTRATION NUMBER: CRD42022315033.


Assuntos
Inteligência Artificial , Opinião Pública , Humanos , Atenção à Saúde , Instalações de Saúde , Ocupações em Saúde
3.
Technol Cancer Res Treat ; 22: 15330338221145141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36604997

RESUMO

Background: Neuroblastoma (NB) is the most common childhood cancer, but doctors are unable to predict its overall survival (OS) rate before surgery. We aimed to predict the OS of NB children with some clinical features obtained from biopsy before surgery. Methods: Clinical features of NB children were retrospectively collected from the Therapeutically Applicable Research to Generate Effective Treatments database. The C-index, area under the receiver operating characteristic curve (AUC), calibration curves, and decision curves analysis were used to estimate nomogram models. Results: A total of 488 NB children were evaluated, and the Boruta algorithm was used to detect risk factors. The results showed that artificial neural networks with selected features were able to predict more than 90% of NB children. Five risk factors were used in the construction of the nomogram, including age at diagnosis, MYCN status, ploidy value, histology, and mitosis-karyorrhexis index (MKI). The C-index of the nomogram in training cohort and validation cohort was 0.716 and 0.731. AUC values for 1-, 3-, and 5-years OS predictions were 0.706, 0.755, and 0.762, respectively, and showed good calibrations. Decision curve analysis indicated a better predictability with the nomogram model based on Cox regression compared with one that included all variables and histology only. Also, the Kaplan-Meier curves showed a significantly higher survival probability in the low-risk group (total score <118.34) versus the high-risk group (total score ≥ 118.34) (p < 0.05) using the nomogram model. Conclusions: A web application based on the nomogram model in the present study can be accessed at https://mdzhou.shinyapps.io/DynNomapp/, which could help doctors make accurate clinical decisions about NB children.


Assuntos
Neuroblastoma , Nomogramas , Criança , Humanos , Estudos Retrospectivos , Prognóstico , Neuroblastoma/diagnóstico , Neuroblastoma/cirurgia , Biópsia
4.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614198

RESUMO

Nitrate Transporter 1/Peptide Transporter Family (NPF) genes encode membrane transporters involved in the transport of diverse substrates. However, little is known about the diversity and functions of NPFs in Brassica rapa. In this study, 85 NPFs were identified in B. rapa (BrNPFs) which comprised eight subfamilies. Gene structure and conserved motif analysis suggested that BrNFPs were conserved throughout the genus. Stress and hormone-responsive cis-acting elements and transcription factor binding sites were identified in BrNPF promoters. Syntenic analysis suggested that tandem duplication contributed to the expansion of BrNPFs in B. rapa. Transcriptomic profiling analysis indicated that BrNPF2.6, BrNPF2.15, BrNPF7.6, and BrNPF8.9 were expressed in fertile floral buds, suggesting important roles in pollen development. Thirty-nine BrNPFs were responsive to low nitrate availability in shoots or roots. BrNPF2.10, BrNPF2.19, BrNPF2.3, BrNPF5.12, BrNPF5.16, BrNPF5.8, and BrNPF6.3 were only up-regulated in roots under low nitrate conditions, indicating that they play positive roles in nitrate absorption. Furthermore, many genes were identified in contrasting genotypes that responded to vernalization and clubroot disease. Our results increase understanding of BrNPFs as candidate genes for genetic improvement studies of B. rapa to promote low nitrate availability tolerance and for generating sterile male lines based on gene editing methods.


Assuntos
Brassica rapa , Brassica rapa/metabolismo , Nitratos/metabolismo , Perfilação da Expressão Gênica , Transportadores de Nitrato , Pólen/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/metabolismo
5.
Cell Death Dis ; 14(1): 44, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36658121

RESUMO

The alteration of cellular energy metabolism is a hallmark of colorectal cancer (CRC). Accumulating evidence has suggested oxidative phosphorylation (OXPHOS) is upregulated to meet the demand for energy in tumor initiation and development. However, the role of OXPHOS and its regulatory mechanism in CRC tumorigenesis and progression remain unclear. Here, we reveal that Prohibitin 2 (PHB2) expression is elevated in precancerous adenomas and CRC, which promotes cell proliferation and tumorigenesis of CRC. Additionally, knockdown of PHB2 significantly reduces mitochondrial OXPHOS levels in CRC cells. Meanwhile, NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1), as a PHB2 binding partner, is screened and identified by co-immunoprecipitation and mass spectrometry. Furthermore, PHB2 directly interacts with NDUFS1 and they co-localize in mitochondria, which facilitates NDUFS1 binding to NADH:ubiquinone oxidoreductase core subunit V1 (NDUFV1), regulating the activity of complex I. Consistently, partial inhibition of complex I activity also abrogates the increased cell proliferation induced by overexpression of PHB2 in normal human intestinal epithelial cells and CRC cells. Collectively, these results indicate that increased PHB2 directly interacts with NDUFS1 to stabilize mitochondrial complex I and enhance its activity, leading to upregulated OXPHOS levels, thereby promoting cell proliferation and tumorigenesis of CRC. Our findings provide a new perspective for understanding CRC energy metabolism, as well as novel intervention strategies for CRC therapeutics.


Assuntos
Neoplasias Colorretais , NADH Desidrogenase , Fosforilação Oxidativa , Proibitinas , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica , Neoplasias Colorretais/genética , NAD/metabolismo , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Oxirredutases/metabolismo , Proteínas Repressoras/metabolismo , Ubiquinona/metabolismo , Proibitinas/genética
6.
World J Emerg Med ; 14(1): 44-48, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36713344

RESUMO

BACKGROUND: Acute pancreatitis (AP) is a complex and heterogeneous disease. We aimed to design and validate a prognostic nomogram for improving the prediction of short-term survival in patients with AP. METHODS: The clinical data of 632 patients with AP were obtained from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The nomogram for the prediction of 30-day, 60-day and 90-day survival was developed by incorporating the risk factors identified by multivariate Cox analyses. RESULTS: Multivariate Cox proportional hazard model analysis showed that age (hazard ratio [HR]=1.06, 95% confidence interval [95% CI] 1.03-1.08, P<0.001), white blood cell count (HR=1.03, 95% CI 1.00-1.06, P=0.046), systolic blood pressure (HR=0.99, 95% CI 0.97-1.00, P=0.015), serum lactate level (HR=1.10, 95% CI 1.01-1.20, P=0.023), and Simplified Acute Physiology Score II (HR=1.04, 95% CI 1.02-1.06, P<0.001) were independent predictors of 90-day mortality in patients with AP. A prognostic nomogram model for 30-day, 60-day, and 90-day survival based on these variables was built. Receiver operating characteristic (ROC) curve analysis demonstrated that the nomogram had good accuracy for predicting 30-day, 60-day, and 90-day survival (area under the ROC curve: 0.796, 0.812, and 0.854, respectively; bootstrap-corrected C-index value: 0.782, 0.799, and 0.846, respectively). CONCLUSION: The nomogram-based prognostic model was able to accurately predict 30-day, 60-day, and 90-day survival outcomes and thus may be of value for risk stratification and clinical decision-making for critically ill patients with AP.

7.
Sci Adv ; 9(4): eadf6277, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36706191

RESUMO

Replication stress is a major source of endogenous DNA damage. Despite the identification of numerous proteins on replication forks to modulate fork or replication machinery activities, it remains unexplored whether noncoding RNAs can localize on stalled forks and play critical regulatory roles. Here, we identify an uncharacterized long noncoding RNA NONMMUT028956 (Lnc956 for short) predominantly expressed in mouse embryonic stem cells. Lnc956 is accumulated on replication forks to prevent fork collapse and preserve genomic stability and is essential for mouse embryogenesis. Mechanistically, it drives assembly of the Lnc956-TRIM28-HSP90B1 complex on stalled forks in an interdependent manner downstream of ataxia telangiectasia and Rad3-related (ATR) signaling. Lnc956-TRIM28-HSP90B1 complex physically associates with minichromosome maintenance proteins 2 (MCM2) to minichromosome maintenance proteins 7 (MCM7) hexamer via TRIM28 and directly regulates the CDC45-MCM-GINS (CMG) helicase retention on chromatin. The regulation of Lnc956-TRIM28-HSP90B1 on CMG retention is mediated by HSP90B1's chaperoning function. These findings reveal a player that actively regulates replisome retention to prevent fork collapse.


Assuntos
DNA Helicases , Replicação do DNA , Animais , Camundongos , DNA Helicases/genética , DNA Helicases/metabolismo , Cromatina , Instabilidade Genômica , Proteína 28 com Motivo Tripartido/genética , Proteína 28 com Motivo Tripartido/metabolismo
8.
Water Sci Technol ; 87(2): 454-468, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36706293

RESUMO

Traditional liquid-solid extraction methods for the removal of zinc ions (Zn(II)) were generally limited by the leakage of extractant and low extraction capacity. The two-component Pickering emulsion hydrogels (PEHGs) in which the synergistic 2-ethylhexyl hydrogen-2-ethylhexylphosphate/tributyl phosphate (EHEHPA/TBP) was encapsulated in a semi-penetrating polymer network (SIPN) structured hydrogels polyacrylamide/sodium alginate (PAM/SA) were prepared by the Pickering emulsions polymerization route. The PEHGs were characterized by FTIR, SEM, TGA, and tensile mechanical measurements, and their self-healing properties were explored. The adsorption performance of PEHGs on Zn(II) was investigated. The results showed that the encapsulation of the extractant reached 95% due to the hydrogels network and nano-silica (nano-SiO2) particle network in PEHGs-15. The critical crashing pressure of PEHGs-15 was 0.084 MPa, and the adsorption after 3 h of healing was only 86% of the original amount. The maximum adsorption capacity of PEHGs-15 on Zn(II) was 76.51 mg/g at pH 5. The functional groups of SA and EHEHPA/TBP enhanced the adsorption capacity of PEHGs-15 by chelating with Zn(II). After five adsorption-desorption cycles, the adsorption capacity of PEHGs-15 exceeded 85% of the initial one. The excellent mechanical properties, self-healing, and regenerative properties of PEHGs-15 offer the potential to remove Zn(II) from the solution.


Assuntos
Hidrogéis , Zinco , Hidrogéis/química , Emulsões , Polímeros , Íons , Adsorção , Concentração de Íons de Hidrogênio
9.
Antioxidants (Basel) ; 12(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36671037

RESUMO

Hyperlipidemia results in endothelial dysfunction, which is intimately associated with disturbed mitochondrial homeostasis, and is a real risk factor for cardiovascular diseases (CVDs). Triphenylphosphonium (TPP+)-HT,&nbsp;constructed by linking a mitochondrial-targeting moiety TPP+ to hydroxytyrosol (HT), enters the cell and accumulates in mitochondria and is thus an important candidate drug for preventing hyperlipidemia-induced endothelial injury. In the present study, we found that TPP-HT has a better anti-inflammatory effect than HT. In vivo, TPP-HT significantly prevented hyperlipidemia-induced adverse changes in the serological lipid panel, as well as endothelial and mitochondrial dysfunction of the thoracic aorta. Similarly, in vitro, TPP-HT exhibited similar protective effects in palmitate (PA)-induced endothelial dysfunction, particularly enhanced expression of the mitochondrial ETC complex II, recovered FoxO1 expression in PA-injured human aorta endothelial cells (HAECs) and promoted FoxO1 nuclear translocation. We further demonstrated that FoxO1 plays a pivotal role in regulating ATP production in the presence of TPP-HT by using the siFoxO1 knockdown technique. Simultaneously, TPP-HT enhanced Nrf2 nuclear translocation, consistent with the in vivo findings of immunofluorescence, and the antioxidant effect of TPP-HT was almost entirely blocked by siNrf2. Concomitantly, TPP-HT's anti-inflammatory effects in the current study were primarily mediated via the p38 MAPK/NF-κB signaling pathway in addition to the FoxO1 and Nrf2 pathways. In brief, our findings suggest that mitochondria-targeted TPP-HT prevents lipotoxicity induced endothelial dysfunction by enhancing mitochondrial function and redox balance by promoting FoxO1 and Nrf2 nuclear translocation.

10.
Int J Infect Dis ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36621753

RESUMO

OBJECTIVES: Fungal keratitis (FK) is a kind of serious corneal infection and penetrating keratoplasty (PKP) is needed when medical therapy fails. Although Nectria haematococca (N. haematococca) is found as endophytes in the roots of some plant species, there has been no report of N. haematococca infection in human. METHODS: We reviewed 46 patients who underwent PKP due to FK in our hospital from July 2021 to December 2021, and there were three patients who had relapsed. The next-generation sequencing (NGS) revealed that all three corneas were infected with N. haematococca. RESULTS: Based on the ocular manifestation and treatment course of three cases, we summarize the characteristics of N. haematococca fungal keratitis: The scope of corneal infection was widespread with severe hypopyon. The effect of local use of fluconazole and voriconazole was not ideal, and PKP was the main treatment. Even after a large-scale corneal lesion resection, the lesion may recur. The recurrence occurred primarily in the second week after PKP. CONCLUSION: This is the first clinical report of N. Haematococca infection in humans. Compared to the other currently known FK caused by the Fusarium solani species complex, N. Haematococca keratitis is more severe and more likely to recur.

11.
Heart Vessels ; 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36598570

RESUMO

Improvements are required in the quality of life (QoL) of patients with ischemia and non-obstructive coronary artery disease (INOCA). Several patients with INOCA experience vascular endothelial dysfunction. However, the relationship between endothelial function and QoL remains unelucidated. This study aimed to initially investigate the relationship between endothelial function and QoL in patients with INOCA. This prospective observational study included 121 patients with INOCA (aged 31-85 years). Vascular endothelial function was assessed by flow-mediated dilatation (FMD) of the peripheral brachial artery. QoL was evaluated using the 36-Item Short-Form Health Survey (SF-36). Patients with INOCA were divided into two groups according to the median FMD change during the 1-year follow-up (group A, ≥ median FMD change cut-off; group B, < median FMD change cut-off). The median change in FMD was 0.92%. The mean baseline SF-36 scores were comparable between the two groups (53.95 ± 6.46 vs. 53.92 ± 4.29, p = 0.98). The QoL at follow-up was better in group A than in group B (56.61 ± 5.50 vs. 53.32 ± 5.58, p = 0.002). The change in FMD (r = 0.34, p < 0.01), rather than FMD at baseline (r = - 0.01, p = 0.89) or follow-up (r = 0.13, p = 0.15), was related to the follow-up SF-36 scores. FMD improvement was an independent predictor of increased QoL (odds ratio, 3.90; 95% confidence interval: 1.59-9.53, p = 0.003). Endothelial function change is associated with QoL, and patients with improved endothelial function have a better QoL than those without.

12.
Anal Biochem ; 660: 114970, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341768

RESUMO

OBJECTIVE: To establish and validate a robust LC-MS/MS method for simultaneously measuring 8-oxoGuo, 8-oxodG, and NMN in serum and urine to evaluate the oxidative stress status. METHODS: A Waters TQ-XS triple quadrupole mass spectrometer system coupled with an Acquity UPLC Primer HSS T3 column was chosen. The clinical performance was verified according to the CLSI C62-A and EP-15 guidelines. Furthermore, matched serum and urine samples from 22 apparently healthy check-ups, 20 patients with atherosclerosis, and 18 individuals with dementia were evaluated. RESULTS: The recovery for serum 8-oxoGuo, urine 8-oxoGuo, serum 8-oxodG, urine 8-oxodG, serum NMN, and urine NMN was 88.8-112.4%, 102.4-114.1%, 88.5-107.7%, 94.9-102.6%, 98.4-108.9%, and 88.5-108.6%, respectively. Based on the inter-assay results, total coefficient of variation, matrix effect, and carryover, the LC-MS/MS method was deemed robust. The limit of quantification was 0.017, 0.018, and 0.150 nmol/L for 8-oxoGuo, 8-oxodG, and NMN, respectively, which are suitable for accurate measurements in human serum and urine samples. Higher 8-oxoGuo and 8-oxodG levels and lower NMN levels, indicative of significantly higher oxidative stress status, were found in patients with dementia compared to healthy subjects. CONCLUSION: We established and validated a robust LC-MS/MS method to simultaneously measure 8-oxoGuo, 8-oxodG, and NMN in serum and urine.


Assuntos
Demência , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , 8-Hidroxi-2'-Desoxiguanosina
14.
Biochem Pharmacol ; 207: 115376, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36513142

RESUMO

Molecular chaperone HSP90 has been considered as a promising target for anti-cancer drug development for years. However, due to the heat shock response induced by the ATP competitive inhibitors against HSP90, the therapeutic efficacies of the compounds are compromised, which consequently restricts the clinical use of HSP90-targeted inhibitors. Therefore, there is a need to discover novel HSP90-targeted modulators which exhibit acceptable inhibition activity against the chaperone and do not induce significant heat shock response in the meantime. Here in this study, we firstly developed a tip-based affinity selection-mass spectrometry platform with optimized experimental conditions/parameters for HSP90-targeted active compound screening, and then applied it to fish out inhibitors against HSP90 from a collection of 2,395 compounds composed of FDA-approved drugs and drug candidates. Dipyridamole, which acts as an anti-thrombotic agent by modulating multiple targets and has a long history of safe use, was identified to interact with HSP90's N-terminal domain. The following conducted biophysical and biochemical experiments demonstrated that Dipyridamole could bind to HSP90's ATP binding pocket and function as an ATP competitive inhibitor of the chaperone. Finally, cellular-based assays including CESTA, cell viability assessment and proteomic analysis etc. were performed to evaluate whether the interaction between HSP90 and Dipyridamole contributes to the anti-tumor effects of the compound. We then found that Dipyridamole inhibits the growth and proliferation of human cancer cells by downregulating cell cycle regulators and upregulating apoptotic cell signaling, which are potentially mediated by the binding of Dipyridamole to HSP90 and to PDEs (phosphodiesterases), respectively.


Assuntos
Antineoplásicos , Neoplasias , Animais , Humanos , Dipiridamol/farmacologia , Proteômica , Proteínas de Choque Térmico HSP90/metabolismo , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Linhagem Celular , Trifosfato de Adenosina/metabolismo
15.
Microbiol Res ; 268: 127290, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36571920

RESUMO

Colletotrichum siamense, a member of Colletotrichum gloeosporioides complex species, is the primary pathogen causing rubber anthracnose, which leads to significant economic loss in natural rubber production. Velvet family proteins are fungal-specific proteins and play an essential role in regulating development and secondary metabolism. In this study, we characterized two velvet proteins CsVosA and CsVelB in C. siamense as the orthologs of VosA and VelB in Aspergillus nidulans. CsVosA is located in the nucleus, and CsVelB displays a localization in both the nucleus and the cytoplasm. Deleting CsvosA or CsvelB results in a slow growth rate, and the CsvelB-knockout mutants also exhibit low mycelial density. CsVosA and CsVelB are involved in regulating chitin metabolism and distribution, leading to the variation in the cell wall integrity of C. siamense. Furthermore, disruption of CsvosA or CsvelB can decrease conidial production and viability, and the ΔCsvosA and ΔCsvelB mutants also lose the ability to produce fruiting bodies. Pathogenicity assays show that deleting CsvosA or CsvelB can lower the virulence, and the two velvet genes are essential for the full virulence of C. siamense. Based on the results of the yeast two-hybrid analysis and bimolecular fluorescence complementation assays, CsVosA can interact with CsVelB and form the complex CsVosA-CsVelB in the conidia of C. siamense, which may play essential roles in maintaining the cell wall integrity and conidial viability. In addition, CsVelB is also involved in regulating melanin production of C. siamense. In conclusion, CsVosA and CsVelB regulate vegetative growth, cell wall integrity, asexual/sexual sporulation, conidial viability and virulence in C. siamense.


Assuntos
Colletotrichum , Borracha , Virulência , Esporos Fúngicos , Borracha/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
16.
Eur J Pharmacol ; 940: 175475, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36563952

RESUMO

Vascular endothelial dysfunction plays a central role in the most dreadful human diseases, including stroke, tumor metastasis, and the coronavirus disease 2019 (COVID-19). Strong evidence suggests that angiotensin II (Ang II)-induced mitochondrial dysfunction is essential for endothelial dysfunction pathogenesis. However, the precise molecular mechanisms remain obscure. Here, polymerase-interacting protein 2 (Poldip 2) was found in the endothelial mitochondrial matrix and no effects on Poldip 2 and NADPH oxidase 4 (NOX 4) expression treated by Ang II. Interestingly, we first found that Ang II-induced NOX 4 binds with Poldip 2 was dependent on cyclophilin D (CypD). CypD knockdown (KD) significantly inhibited the binding of NOX 4 to Poldip 2, and mitochondrial ROS generation in human umbilical vein endothelial cells (HUVECs). Similar results were also found in cyclosporin A (CsA) treated HUVECs. Our previous study suggested a crosstalk between extracellular regulated protein kinase (ERK) phosphorylation and CypD expression, and gallic acid (GA) inhibited mitochondrial dysfunction in neurons depending on regulating the ERK-CypD axis. Here, we confirmed that GA inhibited Ang II-induced NOX 4 activation and mitochondrial dysfunction via ERK/CypD/NOX 4/Poldip 2 pathway, which provide novel mechanistic insight into CypD act as a key regulator of the NOX 4/Poldip 2 axis in Ang II-induced endothelial mitochondrial dysfunction and GA might be beneficial in the treatment of wide variety of diseases, such as COVID-19, which is worthy further research.


Assuntos
COVID-19 , Doenças Vasculares , Humanos , NADPH Oxidase 4/metabolismo , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ciclofilina D/metabolismo , Ciclofilina D/farmacologia , NADPH Oxidases/metabolismo , Estresse Oxidativo , Ácido Gálico/farmacologia , COVID-19/metabolismo , Mitocôndrias , Células Endoteliais da Veia Umbilical Humana
17.
Cell Death Discov ; 8(1): 478, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463209

RESUMO

Acquired Trastuzumab resistance is a complicated and disastrous event for HER2-positive gastric cancer (GC). In this study, we successfully established a GC PDX model with Trastuzumab sensitivity (176P) and induced a homologous model with acquired Trastuzumab resistance (176R), then comprehensively delineated the landscape of Trastuzumab resistance mechanisms using single-cell transcriptome sequencing, as well as protein profiling and genomic variation analysis. According to multi-omics study, different gene expression profiles, rather than genetic changes, contributed to acquired Trastuzumab resistance. The mechanisms underlying acquired Trastuzumab resistance present great complexity as multiple molecules and pathways were involved, including ERBB family, MAPK, PI3K/AKT, JAK/STAT, and cell cycle pathways. Through phenotypical and molecular validation, we found that Trastuzumab combined with HER3-targeted antibody or MEK inhibitor demonstrated excellent antitumor activity and good tolerance, which may serve as promising strategies for overcoming acquired Trastuzumab resistance.

18.
BMC Vet Res ; 18(1): 424, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471338

RESUMO

BACKGROUND: Salmonella as an important food-borne zoonotic bacterial pathogen, infection in ducks is a recessive infection, however, it can also cause high mortality and threat to food safety. Preventing and controlling the infection and transmission of Salmonella in ducks critically require rapid and sensitive detection method. Full-length Salmonella-specific protein PagN was induced and expressed in E.coil BL21 and was purified as an antigen to establish an indirect enzyme-linked immunosorbent assays (iELSA) detection kit. RESULTS: The recombinant PagN protein has a molecular weight of 43 kDa containing a His-tag, was recognized by an anti-Salmonella positive serum by Western blot assay. The optimal concentration of PagN as a coating antigen in the iELISA was 1 µg/mL, and the optimal dilution of enzyme-labeled secondary antibody was 1:4000 (0.025 µg/mL). The cutoff OD450 value was established at 0.268. The iELISA kit showed high selectivity since no cross-reaction with E. coli, Staphylococcus aureus and Streptococcus was observed. iELISA method and Dot-blot test were performed on 100 clinical sera samples collected from duck farms, and the actual coincidence rate was 89% (89/100). 613 duck serum samples from 3 different farms were tested using established method and commercial ELISA kit. The concordance between the two methods was 94.1%. CONCLUSION: Anti-PagN based iELISA can serve as a useful tool for diagnosis of Salmonella infection.


Assuntos
Patos , Escherichia coli , Animais , Sensibilidade e Especificidade , Ensaio de Imunoadsorção Enzimática/veterinária , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas Recombinantes , Anticorpos Antibacterianos , Anticorpos Antivirais
19.
Clin Biochem ; 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36473516

RESUMO

Cerebrospinal fluid (CSF) ß-amyloid (Aß) is important for early diagnosis of Alzheimer's disease (AD). However, the cohort distributions and cut-off values have large variation across different analytical assays, kits, and laboratories. In this review, we summarize the cut-off values and diagnostic performance for CSF Aß1-42 and Aß1-42/Aß1-40, and explore the important effect factors. Based on the Alzheimer's Association external quality control program (AAQC program), the peer group coefficient of variation of manual ELISA assays for CSF Aß1-42 was unsatisfied (>20%). Fully automated platforms with better performance have recently been developed, but still not widely applied. In 2020, the certified reference material (CRM) for CSF Aß1-42 was launched; however, the AAQC 2021-round results did not show effective improvements. Thus, further development and popularization of CRM for CSF Aß1-42 and Aß1-40 are urgently required. Standardizing the diagnostic procedures of AD and related status and the pre-analytical protocols of CSF samples, improving detection performance of analytical assays, and popularizing the application of fully automated platforms are also important for the establishment of uniform cut-off values. Moreover, each laboratory should verify the applicability of uniform cut-off values, and evaluate whether it is necessary to establish its own population- and assay-specific cut-off values.

20.
Curr Med Sci ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36459303

RESUMO

OBJECTIVE: This study analyzed the role of G1 to S phase transition 1 protein (GSPT1) in promoting progression of liver cancer cells. METHODS: A bioinformatics database was used to analyze the expression levels of GSPT1 in liver cancer tissues and the prognosis of patients. Subsequently, Western blotting and quantitative PCR were used to verify the expression levels of GSPT1 between normal hepatocytes and hepatoma cells. We used a CRISPR/Cas9 system to construct knockouts of GSPT1 in HepG2 and HCCLM9 liver cancer cells. The effect of GSPT1 on liver cancer cell migration and invasion was analyzed using flow cytometry, migration, and tumor formation assays. RESULTS: The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset indicated that GSPT1 expression was upregulated in liver cancer cell lines, and patients with liver cancer had poor prognosis. Knockout of GSPT1 in cells significantly inhibited tumor proliferation, cell migration, and growth in vivo. CONCLUSION: In this study, we found that GSPT1 promotes the migration and invasion of liver cancer cells.

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