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1.
Placenta ; 150: 39-51, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38588616

RESUMO

INTRODUCTION: Preeclampsia (PE) is a severe obstetric complication closely associated with placental dysfunction. Placental mesenchymal stem/stromal cells (PMSCs) modulate placental development while PE PMSCs are excessively senescent to disturb placental function. Nevertheless, the senescence mechanism of PE PMSCs remains unclear. METHODS: PE-related single-cell RNA sequencing datasets (GSE173193), data of chip detection (GSE99007) and bulk transcriptome RNA sequencing datasets (GSE75010) were extracted from the GEO database. Firstly, the functional enrichment analyses of the differentially expressed genes (DEGs) in PMSCs were conducted. Then, the clusters of PE PMSCs were distinguished according to the expressions of senescence-related genes (SRGs) by consensus clustering analysis. Cell cycle analysis, senescence ß-galactosidase, Transwell, and tube formation were conducted. Next, the expressions of the senescence-associated secretory phenotype (SASPs) were displayed. The characteristic genes of PE were screened by the least absolute shrinkage and selection operator analysis. CTSZ was suppressed in PMSCs and the cellular senescence levels were evaluated. RESULTS: In this study, The DEGs in PMSCs were closely associated with cellular senescence. The score of SRGs was significantly higher and most of the SASPs were abnormally expressed in the senescent group. Seven characteristic genes of PE were identified, thereinto, CTSZ reduction may accelerate the senescence in PMSCs in vitro. DISCUSSION: Combined with bioinformatic analysis and lab experiments, our study emphatically revealed the abnormal cellular senescence in PE PMSCs, in which CTSZ, one of the PE characteristic genes, regulated the cellular senescence levels in PMSCs. These findings might help to deepen the understanding of the senescence mechanism of PMSCs in PE.

2.
Cell Death Discov ; 10(1): 121, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459014

RESUMO

Histone lactylation has been reported to involve in tumorigenesis and development. However, its biological regulatory mechanism in endometrial carcinoma (EC) is yet to be reported in detail. In the present study, we evaluated the modification levels of global lactylation in EC tissues by immunohistochemistry and western blot, and it was elevated. The non-metabolizable glucose analog 2-deoxy-d-glucose (2-DG) and oxamate treatment could decrease the level of lactylation so as to inhibit the proliferation and migration ability, induce apoptosis significantly, and arrest the cell cycle of EC cells. Mechanically, histone lactylation stimulated USP39 expression to promote tumor progression. Moreover, USP39 activated PI3K/AKT/HIF-1α signaling pathway via interacting with and stabilizing PGK1 to stimulate glycolysis. The results of present study suggest that histone lactylation plays an important role in the progression of EC by promoting the malignant biological behavior of EC cells, thus providing insights into potential therapeutic strategies for endometrial cancer.

3.
Cell Commun Signal ; 22(1): 170, 2024 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459564

RESUMO

Heterogeneous cancer-associated fibroblasts (CAFs) play important roles in cancer progression. However, the specific biological functions and regulatory mechanisms involved in endometrial cancer have yet to be elucidated. We aimed to explore the potential mechanisms of heterogeneous CAFs in promoting endometrial cancer progression. The presence of melanoma cell adhesion molecule (MCAM; CD146) positive CAFs was confirmed by tissue multi-immunofluorescence (mIF), and fluorescence activated cell sorting (FACS). The biological functions were determined by wound healing assays, tuber formation assays and cord formation assays. The effects of CD146+CAFs on endometrial cancer cells were studied in vitro and in vivo. The expression level of interleukin 10 (IL-10) was measured by quantitative real time polymerase chain reaction (qRT-PCR), western boltting and enzyme linked immunosorbent assays (ELISAs). In addition, the transcription factor STAT3 was identified by bioinformatics methods and chromatin immunoprecipitation (ChIP). A subtype of CAFs marked with CD146 was found in endometrial cancer and correlated with poor prognosis. CD146+CAFs promoted angiogenesis and vasculogenic mimicry (VM) in vitro. A xenograft tumour model also showed that CD146+CAFs can facilitate tumour progression. The expression of IL-10 was elevated in CD146+CAFs. IL-10 promoted epithelial-endothelial transformation (EET) and further VM formation in endometrial cancer cells via the janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) signalling pathway. This process could be blocked by the JAK1/STAT3 inhibitor niclosamide. Mechanically, STAT3 can bind to the promoter of cadherin5 (CDH5) to promote its transcription which may be stimulated by IL-10. We concluded that CD146+CAFs could promote angiogenesis and VM formation via the IL-10/JAK1/STAT3 signalling pathway. These findings may lead to the identification of potential targets for antiangiogenic therapeutic strategies for endometrial cancers.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias do Endométrio , Feminino , Humanos , 60489 , Fibroblastos Associados a Câncer/metabolismo , Antígeno CD146/metabolismo , Linhagem Celular Tumoral , Neoplasias do Endométrio/metabolismo , Interleucina-10 , Janus Quinase 1 , Fator de Transcrição STAT3/metabolismo
4.
Int J Surg ; 110(3): 1770-1780, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38126341

RESUMO

BACKGROUND AND AIMS: Partial pancreatectomy, commonly used for chronic pancreatitis, or pancreatic lesions, has diverse impacts on endocrine and metabolism system. The study aims to determine the global prevalence of new-onset, worsening, and resolution of diabetes following partial pancreatectomy. METHODS: The authors searched PubMed, Embase, Web of Science, and Cochrane Library from inception to October, 2023. DerSimonian-Laird random-effects model with Logit transformation was used. Sensitivity analysis, meta-regression, and subgroup analysis were employed to investigate determinants of the prevalence of new-onset diabetes. RESULTS: A total of 82 studies involving 13 257 patients were included. The overall prevalence of new-onset diabetes after partial pancreatectomy was 17.1%. Univariate meta-regression indicated that study size was the cause of heterogeneity. Multivariable analysis suggested that income of country or area had the highest predictor importance (49.7%). For subgroup analysis, the prevalence of new-onset diabetes varied from 7.6% (France, 95% CI: 4.3-13.0) to 38.0% (UK, 95% CI: 28.2-48.8, P <0.01) across different countries. Patients with surgical indications for chronic pancreatitis exhibited a higher prevalence (30.7%, 95% CI: 21.8-41.3) than those with pancreatic lesions (16.4%, 95% CI: 14.3-18.7, P <0.01). The type of surgical procedure also influenced the prevalence, with distal pancreatectomy having the highest prevalence (23.7%, 95% CI: 22.2-25.3, P <0.01). Moreover, the prevalence of worsening and resolution of preoperative diabetes was 41.1 and 25.8%, respectively. CONCLUSIONS: Postoperative diabetes has a relatively high prevalence in patients undergoing partial pancreatectomy, which calls for attention and dedicated action from primary care physicians, specialists, and health policy makers alike.


Assuntos
Diabetes Mellitus , Neoplasias Pancreáticas , Pancreatite Crônica , Humanos , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/cirurgia , Pâncreas/cirurgia , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/cirurgia , Pancreatite Crônica/complicações , Neoplasias Pancreáticas/cirurgia
5.
Mol Carcinog ; 63(3): 384-399, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38116886

RESUMO

Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real-time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull-down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain- and loss-of-function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.


Assuntos
Carcinoma de Células de Transição , MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Invasividade Neoplásica/genética , Proliferação de Células/genética , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral
6.
Dalton Trans ; 53(4): 1497-1505, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38131421

RESUMO

Designing a unique morphology and nanoarchitecture with a heterostructure is regarded as an efficient strategy to achieve lithium-ion batteries (LIBs) with high capacity and cycle life. Herein, N-doped C-encapsulated flower-like NiS/Ni3(BO3)2 heterostructures (NiS/Ni3(BO3)2/NC) with a core-shell morphology are successfully synthesized by a facile general method to improve the rate performance and prolong the cycle life of LIBs. The coated NC layer and core-shell structure with elasticity can relieve the volume expansion during the lithiation/delithiation process to strengthen the stability of the structure. Moreover, the NC layer and NiS/Ni3(BO3)2/NC heterostructure can enhance the electronic conductivity of the electrode and guarantee fast and unimpeded electron transfer channels, thereby improving the electrochemical reaction kinetics. Owing to the synergy of heterostructures and core-shell layer, the as-synthesized NiS/Ni3(BO3)2/NC anode acquires a specific charge capacity of 549 mA h g-1 at 0.2 A g-1 after 100 cycles; meanwhile, a reversible capacity of 322 mA h g-1 can be maintained even at 1 A g-1 after 500 cycles. This study develops a universal interface manipulation strategy for the synthesis of M3B2O6-based or/and other advanced transition metal compound anode materials for the practical applications of LIBs.

7.
Clin Infect Dis ; 77(10): 1468-1475, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37506258

RESUMO

BACKGROUND: Mass tuberculosis (TB) screening has been recommended in certain high-risk populations. However, population-based screening interventions have rarely been implemented. Whether mass screening improves health equity is unknown. METHODS: We implemented a mass TB screening intervention among elderly persons (>60 years old) in Lanxi County, China. Standardized questionnaires, physical examinations, and chest radiographs (CXRs) were administered to all participants. Systematic testing with computed tomography, smear, culture, or Xpert was performed among persons with an abnormal CXR. We assessed TB prevalence per 100 000 persons and constructed multivariable regression models among subgroups that were and were not screened. Medical insurance was categorized as participation in either a basic program with limited coverage or a more comprehensive coverage program. RESULTS: In total, 49 339 individuals (32% of the elderly population in Lanxi) participated in the screening. One hundred fifteen screened persons were diagnosed with TB (233 cases per 100 000 persons), significantly higher than persons not screened (168 cases among 103 979 person-years; prevalence-to-case notification ratio, 1.44 [95% confidence interval {CI}, 1.14-1.83]). This increase was largely driven by diagnosis of asymptomatic disease during mass screening (n = 57 [50% of participants with TB]). Participants with basic medical insurance were much more likely to be diagnosed through mass screening than by passive detection (adjusted odds ratio, 4.52 [95% CI, 1.35-21.28]). CONCLUSIONS: In a population-based, mass TB screening intervention encompassing >30% of the elderly population in a county in rural China, case finding was 44% higher than background detection, driven by diagnosis of TB without recognized symptoms. Importantly, mass screening identified TB in people with limited healthcare options who were less likely to be found through background case detection.


Assuntos
Tuberculose , Humanos , Idoso , Pessoa de Meia-Idade , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Programas de Rastreamento/métodos , Fatores de Risco , China/epidemiologia , Prevalência
8.
J Org Chem ; 88(15): 11150-11160, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37462913

RESUMO

A novel multicomponent cascade cyclization reaction in one pot for the preparation of pyrido[3,2-a]phenoxazin-5-ones from simple o-aminophenols, paraformaldehyde, and enaminones has been established. It is noteworthy that o-aminophenol plays multiple roles serving as both a bis-nucleophile and an iminoquinone precursor, which can in situ generate aminophenoxazinones to undergo the Povarov reaction for the first time to yield pyrido[3,2-a]phenoxazin-5-ones with a high efficiency. Moreover, the photoluminescence of pyrido[3,2-a]phenoxazin-5-ones has polarity sensitivity and features aggregation-induced emission (AIE) characteristics, which is promising for bioimaging and theranostic applications.

9.
ACS Omega ; 8(22): 20116-20124, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37305250

RESUMO

The grafted modification TiO2@SiO2 composite was fabricated by a liquid-phase deposition method with Na2SiO3 and a grafting reaction with a silane coupling agent. First, the TiO2@SiO2 composite was prepared, and the effect of deposition rate and silica content on the morphology, particle size, dispersibility, and pigmentary property of TiO2@SiO2 composites was investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), and ζ-potential. The islandlike TiO2@SiO2 composite had a good particle size and printing performance compared with the dense TiO2@SiO2 composite. The presence of Si was confirmed by EDX elemental analysis and XPS, and a peak at 980 cm-1 belonging to Si-O was observed in the FTIR spectrum, confirming the presence of SiO2 anchored at TiO2 surfaces via Si-O-Ti bonds. Then, the islandlike TiO2@SiO2 composite was modified by grafting with a silane coupling agent. The effect of the silane coupling agent on the hydrophobicity and dispersibility was investigated. The peaks at 2919 and 2846 cm-1 belong to CH2 in the FTIR spectrum, and Si-C in the XPS confirmed the grafting of silane coupling agent to the TiO2@SiO2 composite. The grafted modification of the islandlike TiO2@SiO2 composite using 3-triethoxysilylpropylamine endowed it with weather durability, dispersibility, and good printing performance.

10.
J Org Chem ; 88(13): 9321-9331, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37319376

RESUMO

2-Hydroxy-4-morpholin-2,5-diarylfuran-3(2H)-one derivatives were constructed sequentially using iodine and zinc dust from simple and readily available methyl ketone and morpholine as the starting materials. Under mild conditions, C-C, C-N, and C-O bonds formed in a one-pot synthesis. A quaternary carbon center was successfully constructed, and the active drug fragment morpholine was introduced into the molecule.


Assuntos
Carbono , Iodo , Reação de Cicloadição , Acetona , Iodo/química , Morfolinas , Cetonas/química
11.
Environ Sci Technol ; 57(19): 7410-7420, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37134202

RESUMO

Hot springs represent a major source of arsenic release into the environment. Speciation is typically reported to be dominated by arsenite, arsenate, and inorganic thiolated arsenates. Much less is known about the relevance and formation of methylated thioarsenates, a group with species of high mobility and toxicity. In hot spring samples taken from the Tengchong volcanic region in China, methylated thioarsenates contributed up to 13% to total arsenic. Enrichment cultures were obtained from the corresponding sediment samples and incubated to assess their capability to convert arsenite into methylated thioarsenates over time and in the presence of different microbial inhibitors. In contrast to observations in other environmental systems (e.g., paddy soils), there was no solid evidence, supporting that the sulfate-reducing bacteria contributed to the arsenic methylation. Methanosarcina, the sole genus of methanogens detected in the enrichment cultures, as well as Methanosarcina thermophila TM-1, a pure strain within the genus, did methylate arsenic. We propose that methylated thioarsenates in a typical sulfide-rich hot spring environment like Tengchong form via a combination of biotic arsenic methylation driven by thermophilic methanogens and arsenic thiolation with either geogenic sulfide or sulfide produced by sulfate-reducing bacteria.


Assuntos
Arsênio , Arsenitos , Fontes Termais , Fontes Termais/microbiologia , Metilação , Sulfetos , Sulfatos
12.
Org Lett ; 25(19): 3386-3390, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37154544

RESUMO

A [3 + 1 + 2] cyclization-rearrangement reaction scheme was developed to synthesize pyrimido[1,2-b]indazoles from aryl methyl ketones, 3-aminoindazoles, and gem-diarylethenes. This metal-free process proceeds via a sequential aza-Diels-Alder reaction and Wagner-Meerwein rearrangement, and a possible reaction mechanism was demonstrated based on control experiments. This method exhibits good substrate compatibility and allows simple reaction conditions. Moreover, the products display significant aggregation-induced emission characteristics after simple modifications.

13.
BMC Cancer ; 23(1): 491, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37259038

RESUMO

BACKGROUND: Metabolic reprogramming is one of hallmarks of cancer progression and is of great importance for the tumor microenvironment (TME). As an abundant metabolite, lactate has been found to play a critical role in cancer development and immunosuppression of TME. However, the potential role of lactate metabolism-related genes in endometrial cancer (EC) remains obscure. METHODS: RNA sequencing data and clinical information of EC were obtained from The Cancer Genome Atlas (TCGA) database. Lactate metabolism-related genes (LMRGs) WERE from Molecular Signature Database v7.4 and then compared the candidate genes from TCGA to obtain final genes. Univariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were performed to screen prognostic genes. A lactate metabolism-related risk profile was constructed using multivariate Cox regression analysis. The signature was validated by time-dependent ROC curve analysis and Kaplan-Meier analysis. The relationship between the risk score and age, grade, stage, tumor microenvironmental characteristics, and drug sensitivity was as well explored by correlation analyses. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional analysis between the high and low-risk groups were performed. CCK8, EdU, and clone formation assays were applied to detect the proliferation ability of EC cells, Transwell assay was performed to detect the migration ability of EC cells, and intracellular lactate and glucose content was used to asses lactate metabolism. RESULTS: We constructed a risk signature based on 18 LMRGs. Kaplan-Meier curves confirmed that the high-risk group had poorer prognosis compared to the low-risk group. A nomogram was then constructed to predict the probability of EC survival. We also performed GO enrichment analysis and KEGG pathway functional analysis between the high and low-risk groups, and the outcome revealed that the features were significantly associated with energy metabolism. There was a significant correspondence between LMRGs and tumor mutational load, checkpoints and immune cell infiltration. C1, C2, and C4 were the most infiltrated in the high-risk group. The high-risk group showed increased dendritic cell activation, while the low-risk group showed increased plasma cells and Treg cells. Drug sensitivity analysis showed LMRGs risk was more resistant to Scr kinase inhibitors. We further proved that one of the lactate metabolism related genes, TIMM50 could promote EC cell proliferation, migration and lactate metabolism. CONCLUSION: In conclusion, we have established an effective prognostic signature based on LMRG expression patterns, which may greatly facilitate the assessment of prognosis, molecular features and treatment modalities in EC patients and may be useful in the future translation to clinical applications. TIMM50 was identified as a novel molecule that mediates lactate metabolism in vitro and in vivo, maybe a promising target for EC prognosis.


Assuntos
Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/genética , Metabolismo Energético , Fatores de Risco , Prognóstico , Microambiente Tumoral/genética
14.
ACS Appl Mater Interfaces ; 15(15): 19750-19760, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37018512

RESUMO

Cationic modification of cotton fabric was an effective way to improve the inkjet printing performance with reactive dye ink. However, there were few research studies that focused on the effect of the cationic agent structure, especially the alkyl chain length of the quaternary ammonium salt (QAS) cationic modifier, on the K/S value, dye fixation, and diffusion of inkjet-printed cotton fabric. In our work, different alkyl chain lengths of QAS were synthesized, and the inkjet printing performance of cationic cotton fabrics treated with different QASs was investigated. Compared with untreated cotton fabric, the K/S value and dye fixation of cationic cotton fabric treated with different QASs improved by 10.7 to 69.3% and 16.9 to 27.7%, respectively. With the increase in alkyl chain length of QAS, the interaction force between anionic reactive dyes and cationic QAS gradually increased mainly due to the fact that more N-positive ions on the quaternary ammonium group were exposed under the action of steric hindrance of alkyl chain length through the XPS spectrum. The electrostatic attraction between cationic cotton and reactive dye contributed to the diffusion of reactive dye into the fiber interior and enhanced the reaction probability of nucleophilic substitution reaction between monochlorotriazine reactive dye and the hydroxyl group of cotton fabric. The antibacterial result of the inkjet-printed cotton fabric indicated that when the alkyl chain length of QAS was higher than 8, the cationic cotton fabric obtained good antibacterial property.

15.
Org Lett ; 25(13): 2294-2299, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-36951380

RESUMO

A concise and efficient hydrodefluorination process was developed for the synthesis of gem-difluoroalkenes. This reaction employs rongalite as a masked proton source and does not require any additional catalysts or reductants. Notably, trifluoromethyl alkenes having both terminal and internal double bonds are compatible with this process, allowing for a wider range of substrates. The successful late-stage functionalizations of pharmaceuticals and gram-scale syntheses were used to demonstrate the viability of this method.

16.
J Org Chem ; 88(6): 3760-3771, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36821870

RESUMO

Concise synthesis of functionalized quinolines has received continuous research attention owing to the biological importance and synthetic potential of bicyclic N-heterocycles. However, synthetic routes to the 2,4-unsubstituted alkyl quinoline-3-carboxylate scaffold, which is an important motif in drug design, remain surprisingly limited, with modular protocols that proceed from readily available materials being even more so. We herein report an acidic I2-DMSO system that converts readily available aspartates and anilines into alkyl quinoline-3-carboxylate. This method can be extended to a straightforward synthesis of 3-arylquinolines by simply replacing the aspartates with phenylalanines. Mechanistic studies revealed that DMSO was activated by HI via a Pummerer reaction to provide the C1 synthon, while the amino acid catabolized to the C2 synthon through I2-mediated Strecker degradation. A formal [3 + 2 + 1] annulation of these two concurrently generated synthons with aniline was responsible for the selective formation of the quinoline core. The synthetic utility of this protocol was illustrated by the efficient synthesis of human 5-HT4 receptor ligand. Moreover, an unprecedented chemoselective synthesis of 2-deuterated, 3-substituted quinoline, featuring this reaction, has been established.

17.
Org Biomol Chem ; 21(10): 2091-2095, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36809309

RESUMO

We herein report an efficient synthesis of 2-aroyl-3-arylquinolines from phenylalanines and anilines. The mechanism involves I2-mediated Strecker degradation enabled catabolism and reconstruction of amino acids and a cascade aniline-assisted annulation. Both DMSO and water act as oxygen sources in this convenient protocol.

18.
Comb Chem High Throughput Screen ; 26(8): 1488-1502, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36200154

RESUMO

BACKGROUND: Endometrial cancer (EC) is one of the most normal malignancies globally. Growing evidence suggests epithelial-mesenchymal transition (EMT) related markers are closely correlated with poor prognosis of EC. However, the relationship between multiple EMT-associated long non-coding RNAs (lncRNAs) and the prognosis of EC has not yet been studied. METHODS: The transcriptome data and clinical information of EC cases were obtained from The Cancer Genome Atlas (TCGA). Then, we identified differentially expressed EMT-associated lncRNAs between tumor and normal tissue. Univariate cox regression analysis and multivariate stepwise Cox regression analysis were applied to identify EMT-associated lncRNAs related to overall survival (OS). Kaplan-Meier curve, receiver operating characteristic (ROC), nomograms and multi-index ROC curves were further established to evaluate the performance of the prognostic signature. In addition, we also investigated the distribution of immune cell characteristics, sensitivity to immune checkpoint inhibitor (ICI) and chemotherapeutics, and tumor mutation burden (TMB) between high- and low-risk scores predicated on a prognostic model. RESULTS: We established nine EMT-associated lncRNA signatures to predict the OS of EC, the area under the ROC curve (AUC) of the risk score has better values than other clinical characteristics, indicating the accuracy of the prognostic signature. As revealed by multivariate Cox regression, the prognosis model independently predicted EC prognosis. Moreover, the signature and the EMTassociated lncRNAs showed significant correlations with other clinical characteristics,including. Multi-index ROC curves for estimating 1-, 3- and 5-year overall survival (OS) of EC patients showed good predictive accuracy with AUCs of 0.731, 0.791, and 0.782, respectively. The highrisk group had specific tumor immune infiltration, insensitive to ICI, higher chemotherapeutics sensitivity and higher expression of TP53 mutation. Finally, the five lncRNAs of signature were further verified by qRT-PCR. CONCLUSION: We constructed an EMT-associated lncRNA signature that can predict the prognosis of EC effectively, and the prognostic signature also played an essential role in the TME; thus, the establishment of an EMT-associated lncRNA signature may provide new perspectives for the treatment of EC.


Assuntos
Neoplasias do Endométrio , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Análise Multivariada , Mutação
19.
Mol Carcinog ; 62(3): 303-318, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36468837

RESUMO

Kinesin family member 4A (KIF4A) belongs to the kinesin superfamily proteins, which are closely associated with mitophagy. Nonetheless, the role of KIF4A in endometrial cancer (EC) remains poorly characterized. The present study showed that KIF4A not only was upregulated but also predicted poor prognosis in patients with EC. KIF4A knockdown in EC cells resulted in attenuated proliferative capacity in vitro and in vivo. Transcriptome sequencing and gene function analysis revealed that KIF4A contributed to the maintenance of EC cells' genomic stability and that KIF4A knockdown induced the DNA damage response, cell cycle arrest, and apoptosis. Mechanistically, KIF4A interacted with TPX2 (a protein involved in DNA damage repair to cope with the replication pressure) to enhance its stability via inhibition of TPX2 ubiquitination and eventually ensured the genomic stability of EC cells during mitosis. Taken together, our results indicated that KIF4A functions as a tumor oncogene that facilitates EC progression via the maintenance of genomic stability. Therefore, targeting the KIF4A/TPX2 axis may provide new concepts and strategies for the treatment of patients with EC.


Assuntos
Neoplasias do Endométrio , Cinesinas , Humanos , Feminino , Proteólise , Cinesinas/genética , Cinesinas/metabolismo , Pontos de Checagem do Ciclo Celular , Reparo do DNA , Neoplasias do Endométrio/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 287(Pt 2): 122072, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36375287

RESUMO

Spectrometers are essential analytical devices for analyzing fluid samples in biological, environmental, and disease diagnostic applications. However, the relatively high cost, the lack of portability, and the requirement for a constant power supply of bulky laboratory instruments limit their on-site applications. Herein, a wireless, cost-effective, open-source, and handheld spectrometer was designed and fabricated to realize the colorimetric and fluorescence analyses. It was built from off-the-shelf electronics utilizing 3D printing technology. The assembled device costs as little as $50. It has an overall dimension of 5 × 5 × 8 cm and an overall weight of only 130 g, which can easily fit in the palm of an adult's hand. It can detect light waves in the 405-690 nm range and transmit the read data to the corresponding SpecAnalysis Android application via Bluetooth. The feasibility of the device was demonstrated by the optical detection of Cu(II), bovine serum albumin, and calf thymus DNA. The sensitivity and detection limits of this device were comparable to those of commercial research-grade spectrophotometers and fluorescence spectrometers. The results suggest that the handheld spectrometer can be applied to detect a variety of substances, not limited to quantitative analysis of a specific individual compound.


Assuntos
Colorimetria , Refratometria , Espectrometria de Fluorescência/métodos , Impressão Tridimensional , Soroalbumina Bovina
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