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1.
ACS Omega ; 9(31): 33679-33691, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39130577

RESUMO

Low-oxygen (oxygen concentration below 18.5%) phenomena often occur in the top coal caving working face of ultrathick coal seams, posing a serious threat to the safety of workers. The characteristics of oxygen consumption and gas production at low-constant temperature and the corresponding functional group evolution of residual coal in goaf were studied by temperature-programmed and infrared spectrum experiments. The influence of different factors on the emission of low-oxygen gases was studied through numerical calculation. The results show that low-temperature oxygen consumption and gas production occurred when the coal was about 40 °C. When the temperature was constant, the oxygen consumption and gas production rate increased with the extension of time. In the early stage of coal oxidation, the aliphatic C-H components were attacked by oxygen molecules and reacted with them. The asymmetric methyl and methylene groups were more likely to oxidize and produce carbonyl compounds. With the increase of nitrogen injection, the overall width of the oxidation zone (oxygen concentration was defined as 10-18%) narrowed, and the range of the oxidation zone moved forward from the depth of the goaf. The oxygen concentration in the air return corner decreased gradually, and the low-oxygen area in the air return corner expanded gradually. The distance between the low-oxygen area of the working face and the air intake corner was gradually shortened. With the increase of air intake, the width of the oxidation zone increased and moved to the depth of goaf, and the degree of low oxygen in the air return corner increased. The research results are of great significance for the understanding and prevention of the low-oxygen phenomenon in ultrathick coal seams.

2.
Heliyon ; 10(12): e32952, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38994119

RESUMO

Sensorineural hearing loss (SNHL) is a prevalent condition in otolaryngology. A key obstacle is finding effective strategies for regenerating damaged cochlear hair cells in adult animals. A practical and reliable approach has been developed to create a superior cell source for stem cell transplantation in the inner ear to treat SNHL. Atoh1 is involved in the differentiation of neurons, intestinal secretory cells, and mechanoreceptors including auditory hair cells, and thus plays an important role in neurogenesis. Lentivirus-mediated transfection of bone marrow mesenchymal stem cells (BMSCs) was utilized to achieve stable expression of the essential transcription factor Atoh1, which is crucial for developing auditory hair cells without compromising cell survival. By manipulating the induction conditions through altering the cell growth environment using anti-adherent culture, the synergistic impact of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) was effectively applied to significantly improve the differentiation efficiency of bone marrow-derived mesenchymal stem cells (BMSC) into neural stem cells (NSCs) following Atoh1 transfection, thereby reducing the induction time. The study indicated that the newly proposed transdifferentiation method effectively transformed BMSCs into NSCs in a controlled environment, presenting a potential approach for stem cell transplantation to promote hair cell regeneration.

3.
Med Mol Morphol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914690

RESUMO

Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course and poor response to treatment. Primary gastric histiocytic sarcoma is rarer and just reported sporadically.Histiocytic sarcoma is a rare neoplasm of mature histiocytes with an aggressive clinical course and poor response to treatment. Primary gastric histiocytic sarcoma is rarer and just reported sporadically. A case of a 71-year-old female admitted with a one-year history of upper abdominal pain exacerbated after meals. After CT scans revealed a bulged mass at the lesser curvature of the gastric body, the patient underwent endoscopic submucosal dissection. Microscopically, non-cohesive neoplastic cells diffusely infiltrated lamina propria and submucosa, and diffusely expressed LCA, CD4, CD163, CD68 (KP1), Cyclin D1, Lysozyme, and Vimentin. PD-L1 (22CS) expression evaluated as CPS 60. The final pathological diagnosis was gastric histiocytic sarcoma. Subsequently, next-generation sequencing identified a nonsense mutation in exon 21 of NF1 gene [c.2446C > T (p.R816*)] and the TUBB3 gene amplification (copy number: 4.55). The patient refused further treatment and died of the tumor half a year later. This case broadens the spectrum of differential diagnosis of gastric cancer and emphasizes the value of immunohistochemical and molecular tests in the accurate diagnosis of histiocytic sarcoma. Furthermore, we performed literature review of 11 cases of gastric histiocytic sarcoma so as to strengthen the understanding of the clinicopathologic features, treatment, and prognosis.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38867700

RESUMO

Cancer is a leading cause of death worldwide, and the identification of biomarkers and subtypes that can predict the long-term survival of cancer patients is essential for their risk stratification, treatment, and prognosis. However, there are currently no standardized tools for exploring cancer biomarkers or subtypes. In this study, we introduced Cancer Biomarker and Subtype Profiler (CBioProfiler), a web server and standalone application that includes two pipelines for analyzing cancer biomarkers and subtypes. The cancer biomarker pipeline consists of five modules for identifying and annotating cancer survival-related biomarkers using multiple survival-related machine learning algorithms. The cancer subtype pipeline includes three modules for data preprocessing, subtype identification using multiple unsupervised machine learning methods, as well as subtype evaluation and validation. CBioProfiler also includes CuratedCancerPrognosisData, a novel R package that integrates reviewed and curated gene expression and clinical data from 268 studies. These studies cover 43 common blood and solid tumors and draw upon 47,686 clinical samples. The web server is available at https://www.cbioprofiler.com/ and https://cbioprofiler.znhospital.cn/CBioProfiler/, and the standalone app and source code can be found at https://github.com/liuxiaoping2020/CBioProfiler.

6.
Front Oncol ; 14: 1387735, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720807

RESUMO

Background: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children and single nucleotide polymorphisms(SNPs) in certain genes influence risk of RMS. Although FOXO3 had been reported in multiple cancers including RMS, the role of FOXO3 polymorphisms in RMS remains unclear. In this case-control study, we evaluated the association of FOXO3 SNPs with RMS risk and prognosis in children. Methods: Four FOXO3 SNPs(rs17069665 A>G, rs4946936 T>C, rs4945816 C>T and rs9400241 C>A) were genotyped in 110 RMS cases and 359 controls. The associations between FOXO3 polymorphisms and RMS risk were determined by odds ratios(ORs) with 95% confidence intervals(CIs). The associations of rs17069665 and rs4946936 with overall survival in RMS children were estimated using the Kaplan-Meier method and log-rank test. Functional analysis in silico was performed to estimate the probability that rs17069665 and rs4946936 might influence the regulation of FOXO3. Results: We found that rs17069665 (GG vs. AA+AG, adjusted OR=2.96; 95%CI [1.10-3.32]; P=0.010) and rs4946936 (TC+CC vs. TT, adjusted OR=0.48; 95%CI [0.25-0.90]; P=0.023) were related to the increased and decreased RMS risk, respectively. Besides, rs17069665(P<0.001) and rs4946936(P<0.001) were associated with decreased and increased overall survival in RMS patients, respectively. Functional analysis showed that rs17069665 and rs4946936 might influence the transcription and expression of FOXO3 via altering the bindings to MYC, CTCF, and/or RELA. Conclusions: This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.

7.
BMC Urol ; 24(1): 87, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627797

RESUMO

JC polyomavirus (JCPyV) is a human polyomavirus that can establish lifelong persistent infection in the majority of adults. It is typically asymptomatic in immunocompetent individuals. However, there is a risk of developing progressive multifocal leukoencephalopathy (PML) in immunocompromised or immunosuppressed patients. Though JCPyV commonly resides in the kidney-urinary tract, its involvement in urinary system diseases is extremely rare. Here, we reported a case of a 60-year-old male patient with coronavirus disease 2019 (COVID-19) infection who developed hemorrhagic cystitis after receiving treatment with nirmatrelvir 300 mg/ritonavir 100 mg quaque die (QD). Subsequent metagenomic next-generation sequencing (mNGS) confirmed the infection to be caused by JCPyV type 2. Then, human immunoglobulin (PH4) for intravenous injection at a dose of 25 g QD was administered to the patient. Three days later, the hematuria resolved. This case illustrates that in the setting of compromised host immune function, JCPyV is not limited to causing central nervous system diseases but can also exhibit pathogenicity in the urinary system. Moreover, mNGS technology facilitates rapid diagnosis of infectious etiology by clinical practitioners, contributing to precise treatment for patients.


Assuntos
COVID-19 , Cistite Hemorrágica , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Infecções por Polyomavirus , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/complicações , Vírus JC/fisiologia , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/diagnóstico
8.
Bioorg Chem ; 147: 107358, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38626490

RESUMO

VEGFR-2 is an attractive target for the development of anti-tumor drugs and plays a crucial role in tumor angiogenesis. This study reports a series of novel thiophene-3-carboxamide derivatives based on PAN-90806 as VEGFR-2 inhibitors, among which compound 14d exhibits excellent anti-proliferative activity against HCT116, MCF7, PC3, and A549 cell lines, and has effective VEGFR-2 inhibitory activity with an IC50 value of 191.1 nM. Additionally, CETSA results indicated that VEGFR-2 was a relevant target of compound 14d in the cell lines, and compound 14d could also inhibit VEGFR-2 protein phosphorylation in A549 cell line. Furthermore, compound 14d inhibited colony formation, cell migration, and HUVECs tube formation in a dose-dependent manner. The mechanism by which 14d induced cancer cell death involves blocking the cell cycle, increasing ROS production, inducing apoptosis, and dose-dependently reducing the levels of phosphorylated ERK and MEK. Molecular docking and molecular dynamics simulations had shown that compound 14d could stably bind to the active site of VEGFR-2. These results confirmed that compound 14d might be a promising lead compound for anti-angiogenesis.


Assuntos
Inibidores da Angiogênese , Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Proteínas Quinases , Tiofenos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Tiofenos/farmacologia , Tiofenos/química , Tiofenos/síntese química , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/química , Inibidores da Angiogênese/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Estrutura Molecular , Descoberta de Drogas , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral
9.
Am J Otolaryngol ; 45(4): 104301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688091

RESUMO

OBJECTIVE: This study aimed to compare the efficacy of balloon Eustachian tuboplasty (BET) plus tympanostomy tube insertion (TTI) and simple TTI for postirradiation otitis media with effusion (OME) in patients with nasopharyngeal carcinoma. METHOD: This study included 36 patients (51 ears) with OME after the first radiotherapy course for nasopharyngeal carcinoma and categorized them into the BET + TTI and simple TTI groups. Effective rates, pure tone hearing threshold, Eustachian tube function score, and complication incidences were compared. RESULTS: The effective rates of the BET+TTI and TTI groups were 93.75 % and 75 %, respectively, with no statistically significant difference (P = 0.29). The pure tone hearing threshold examination at 9 months postoperatively revealed significantly lower mean air-pure tone and air-bone gap in both the BET + TTI and TTI groups than preoperatively. Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) scores at every postoperative visit were significantly higher than preoperative scores in the two groups (all P < 0.05); ETDQ-7 score reduction in the BET + TTI group at 3, 9, and 12 months postoperatively was significantly higher than that in the TTI group. Otorrhea and recurrence both occurred in the BET+TTI and TTI groups, but the BET+TTI group demonstrated a lower incidence. CONCLUSION: BET + TTI is an effective treatment method for postirradiation OME.


Assuntos
Tuba Auditiva , Ventilação da Orelha Média , Neoplasias Nasofaríngeas , Otite Média com Derrame , Humanos , Tuba Auditiva/cirurgia , Otite Média com Derrame/etiologia , Otite Média com Derrame/cirurgia , Masculino , Feminino , Ventilação da Orelha Média/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirurgia , Adulto , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/cirurgia , Audiometria de Tons Puros , Idoso , Estudos Retrospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/cirurgia
10.
Front Oncol ; 14: 1335009, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651156

RESUMO

Background: Based on pharmacoeconomics, drug availability and actual treatment, optimal treatment regimens for Chinese non-small-cell lung carcinoma (NSCLC) patients over 70 years old are needed. Methods: This multicenter, single-arm pilot trial enrolled patients with advanced non-squamous NSCLC who refused systemic chemotherapy. Eligible patients received anlotinib (12 mg/day, d1-14, Q3W) until disease progression, intolerant toxicities, or withdrawal from the study. The primary endpoint was progression-free survival (PFS). Results: Forty-nine patients were screened between January 2019 and September 2021, of whom 40 patients were eligible. The median age was 76 years. With a median follow-up period of 16.20 (95% CI: 8.77, 25.10) months, the median PFS was 5.45 months (95% CI: 3.52-9.23) and the median overall survival was 10.32 months (95% CI: 6.44-12.78). Three patients achieved a partial response and 34 had stable disease, with an objective response rate of 7.5% and a disease control rate of 92.5%. Thirty-three (82.5%; 33/40) patients reported treatment-related adverse events (TRAEs) of any grade, and the incidence rate of grade ≥3 TRAEs was 35% (14/40). The most common grade ≥3 TRAEs were hypertension (4/40; 10.0%), hand-foot syndrome (3/40; 7.5%), and proteinuria (2/40; 5.0%). Conclusion: Anlotinib treatment was feasible and safe in Chinese elderly patients with advanced non-squamous NSCLC who did not receive any systemic chemotherapy.

11.
Turk Neurosurg ; 34(3): 407-414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650553

RESUMO

AIM: To evaluate and compare clinical outcomes between the posterior short-segment pedicle fixation with injured vertebra fixation (PSPFI) and fixation without injured vertebra fixation (PSPF) for thoracolumbar burst fracture (TLBF). MATERIAL AND METHODS: In this retrospective study, a total of 78 patients with TLBF were included and assigned to PSPFI (n=46) and PSPF (n=32) groups. The operative time, blood loss, perioperative complications, Oswestry disability index (ODI), and visual analog pain score (VAS) were examined immediately after surgery, 1 month, 3 months, and 1 year after surgery. Moreover, the postoperative vertebral height correction rate and postoperative Cobb angle correction rate were examined immediately and 1 year after surgery, as well as the corrected vertebral height loss rate and Cobb angle correction loss rate. RESULTS: No significant difference was identified in terms of operative time, blood loss, perioperative complications, ODI, and VAS after surgery (p > 0.05) between the PSPFI and PSPF groups. Moreover, the postoperative vertebral height correction rate and postoperative Cobb angle correction rate showed no difference between the groups as well. However, the PSPFI group had a significantly lower loss rate in terms of corrected vertebral height loss rate and Cobb angle correction loss rate than the PSPF group 1 year after surgery (p < 0.05). CONCLUSION: PSPFI and PSPF achieve similar clinical outcomes. However, posterior short-segment pedicle fixation with injured vertebra significantly maintains vertebral height correction rate and Cobb angle correction rate, which serve as a better choice for the treatment of TLBF.


Assuntos
Fixação Interna de Fraturas , Vértebras Lombares , Fraturas da Coluna Vertebral , Vértebras Torácicas , Humanos , Estudos Retrospectivos , Masculino , Fraturas da Coluna Vertebral/cirurgia , Feminino , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Fixação Interna de Fraturas/métodos , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Adulto Jovem , Fusão Vertebral/métodos
12.
J Ovarian Res ; 17(1): 79, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38610028

RESUMO

OBJECTIVE: IR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies. METHODS: We retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR scores as a phenotypic marker. Gene refinement was executed through the LASSO, SVM, and Boruta feature selection algorithms. qPCR was carried out on selected samples to confirm findings. We predicted both miRNA and lncRNA targets using the ENCORI database, which facilitated the construction of a ceRNA network. Lastly, a drug-target network was derived from the CTD. RESULTS: Thirteen genes related to insulin resistance in PCOS were identified via WGCNA analysis. LASSO, SVM, and Boruta algorithms further isolated CAPN2 as a notably upregulated gene, corroborated by biological verification. The ceRNA network involving lncRNA XIST and hsa-miR-433-3p indicated a possible regulatory link with CAPN2, supported by ENCORI database. Drug prediction analysis uncovered seven pharmacological agents, most being significant regulators of the endocrine system, as potential candidates for addressing insulin resistance in PCOS. CONCLUSIONS: This study highlights the pivotal role of CAPN2 in insulin resistance within the context of PCOS, emphasizing its importance as both a critical biomarker and a potential therapeutic target. By identifying CAPN2, our research contributes to the expanding evidence surrounding the CAPN family, particularly CAPN10, in insulin resistance studies beyond PCOS. This work enriches our understanding of the mechanisms underlying insulin resistance, offering insights that bridge gaps in the current scientific landscape.


Assuntos
Resistência à Insulina , MicroRNAs , Síndrome do Ovário Policístico , RNA Longo não Codificante , Humanos , Feminino , Resistência à Insulina/genética , Síndrome do Ovário Policístico/genética , RNA Longo não Codificante/genética , Algoritmos , Biologia Computacional , Calpaína/genética
13.
Comput Struct Biotechnol J ; 23: 1051-1064, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38455068

RESUMO

Gastric cancer (GC) poses a significant health challenge worldwide, necessitating the identification of predictive biomarkers to improve prognosis. Dysregulated lipid metabolism is a well-recognized hallmark of tumorigenesis, prompting investigation into apolipoproteins (APOs). In this study, we focused on apolipoprotein D (APOD) following comprehensive analyses of APOs in pan-cancer. Utilizing data from the TCGA-STAD and GSE62254 cohorts, we elucidated associations between APOD expression and multiple facets of GC, including prognosis, tumor microenvironment (TME), cancer biomarkers, mutations, and immunotherapy response, and identified potential anti-GC drugs. Single-cell analyses and immunohistochemical staining confirmed APOD expression in fibroblasts within the GC microenvironment. Additionally, we independently validated the prognostic significance of APOD in the ZN-GC cohort. Our comprehensive analyses revealed that high APOD expression in GC patients was notably associated with unfavorable clinical outcomes, reduced microsatellite instability and tumor mutation burden, alterations in the TME, and diminished response to immunotherapy. These findings provide valuable insights into the potential prognostic and therapeutic implications of APOD in GC.

14.
J Cancer ; 15(6): 1762-1769, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370381

RESUMO

Background: The potential relation of methyltransferase-like gene polymorphisms and epithelial ovarian cancer (EOC) remains unclear. Methods: Five SNPs (METTL5 rs3769767 A>G, METTL16 rs1056321 T>C, METTL5 rs10190853 G>A, METTL5 rs3769768 G>A and METTL16 rs11869256 A>G) of methyltransferase-like genes was selected trough NCBI dbSNP database. Two hundred and eighty-eight cases and 361 controls were enrolled from three hospitals in South China to conduct the case-control study. Genomic DNA was abstracted from peripheral blood and genotyped through a TapMan assay. Stratified analysis was conducted to explore the association of rs10190853, rs3769768, rs11869256 genotype and EOC susceptibility. The combination analysis was adopted to evaluate the relation between inferred haplotypes of the METTL5, METTL16 genes and EOC risk. Multifactor dimensionality reduction (MDR) analysis was performed to verify the interaction of SNPs. Results: Among the five analyzed SNPs, METTL5 rs3769768 AA exhibited a significant association with increased EOC risk, while METTL5 rs10190853 GA, METTL16 rs11869256 GA was certified to decrease the susceptibility of EOC. The stratified analysis further revealed the harmful effect of METTL5 rs3769768 AA in EOC patients. On the contrary, METTL16 rs11869256 AG/GG and METTL5 rs10190853 AA showed the reduced risk of EOC in patients of specific subgroups. Combination analysis identified that haplotypes AAA highly connected with reduced risk of EOC. MDR analysis revealed that these SNPs existed no specific interactions. Conclusion: METTL5 rs3769768 was related to increased risk of EOC. METTL5 rs10190853 and METTL16 rs11869256 decreased the susceptibility in EOC. METTL5 and METTL16 could be potential target of molecular therapy and prognosis markers.

15.
Research (Wash D C) ; 7: 0324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405130

RESUMO

Mitochondrial fission promotes glioma progression. The function and regulation mechanisms of lncRNAs in glioma mitochondrial fission are unclear. The expression of LINC00475 and its correlation with clinical parameters in glioma were analyzed using bioinformatics. Then, in vitro and in vivo assays were performed to explore the function of spliced variant LINC00475 (LINC00475-S) in gliomas. To explore the mechanisms, RNA-seq, MeRIP, RIP, pulldown-IP, dCas9-ALKBH5 editing system, LC/MS, and Western blotting were utilized. LINC00475 was confirmed to be overexpressed and with higher frequencies of AS events in gliomas compared to normal brain tissue and was associated with worse prognosis. In vitro and animal tumor formation experiments demonstrated that the effect of LINC00475-S on proliferation, metastasis, autophagy, and mitochondrial fission of glioma cells was significantly stronger than that of LINC00475. Mechanistically, METTL3 induced the generation of LINC00475-S by splicing LINC00475 through m6A modification and subsequently promotes mitochondrial fission in glioma cells by inhibiting the expression of MIF. Pull-down combined LC/MS and RIP assays identified that the m6A recognition protein HNRNPH1 bound to LINC00475 within GYR and GY domains and promoted LINC00475 splicing. METTL3 facilitated HNRNPH1 binding to LINC00475 in an m6A-dependent manner, thereby inducing generation of LINC00475-S. METTL3 facilitated HNRNPH1-mediated AS of LINC00475, which promoted glioma progression by inducing mitochondrial fission. Targeting AS of LINC00475 and m6A editing could serve as a therapeutic strategy against gliomas.

16.
Sheng Wu Gong Cheng Xue Bao ; 40(2): 496-506, 2024 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-38369836

RESUMO

The conventional peptide substrates of SARS-CoV-2 main protease (Mpro) are frequently associated with high cost, unstable kinetics, and multistep synthesis. Hence, there is an urgent need to design affordable and stable Mpro substrates for pharmacological research. Herein, we designed a functional Mpro substrate based on a dimerization-dependent red fluorescent protein (ddRFP) for the evaluation of Mpro inhibitors in vitro. The codon-optimized DNA fragment encoding RFP-A1 domain, a polypeptide linker containing Mpro cleavage sequence (AVLQS), and the RFP-B1 domain was subcloned into the pET-28a vector. After transformation into Escherichia coli Rosetta(DE3) cells, the kanamycin resistant transformants were selected. Using a low temperature induction strategy, most of the target proteins (ddRFP-M) presented in the supernatant fractions were collected and purified by a HisTrapTM chelating column. Subsequently, the inhibition of Mpro by ensitrelvir and baicalein was assessed using ddRFP-M assay, and the biochemical properties of ddRFP-M substrate were analyzed. Our results showed that the fluorogenic substrate ddRFP-M was successfully prepared from E. coli cells, and this biosensor exhibited the expected specificity, sensitivity, and reliability. In conclusion, the production of the fluorogenic substrate ddRFP-M provides an expedient avenue for the assessment of Mpro inhibitors in vitro.


Assuntos
Técnicas Biossensoriais , COVID-19 , Proteases 3C de Coronavírus , Humanos , Dimerização , Proteína Vermelha Fluorescente , SARS-CoV-2/genética , Escherichia coli/genética , Corantes Fluorescentes , Reprodutibilidade dos Testes , Peptídeos , Inibidores de Proteases , Simulação de Acoplamento Molecular
17.
J Matern Fetal Neonatal Med ; 37(1): 2294701, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38177060

RESUMO

OBJECTIVE: This study aimed to analyze the effect of low-molecular-weight heparin (LMWH) on the decidualization of stromal cells in early pregnancy and explore the effect of LMWH on pregnancy outcomes. METHODS: Recurrent spontaneous abortion (RSA) mouse model (CBA/J × DBA/2) and normal pregnant mouse model (CBA/J × BALB/c) were established. The female mice were checked for a mucus plug twice daily to identify a potential pregnancy. When a mucus plug was found, conception was considered to have occurred 12 h previously. The pregnant mice were divided randomly into a normal pregnancy control group, an RSA model group, and an RSA + LMWH experimental group (n = 10 mice in each group). Halfway through the 12th day of pregnancy, the embryonic loss of the mice was observed; a real-time quantitative polymerase chain reaction was used to detect the messenger ribonucleic acid (mRNA) expressions of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) in the decidua of the mice. Additionally, the decidual tissues of patients with RSA and those of normal women in early pregnancy who required artificial abortion were collected and divided into an RSA group and a control group. Decidual stromal cells were isolated and cultured to compare cell proliferation between the two groups, and cellular migration and invasion were detected by membrane stromal cells. Western blotting was used to detect the protein expressions of proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteinase- (MMP) 2, and MMP-7 in stromal cells treated with LMWH. RESULTS: Compared with the RSA group, LMWH significantly reduced the pregnancy loss rate in the RSA mice (p < 0.05). Compared with the RSA group, the LMWH + RSA group had significantly higher expression levels of PRL and IGFBP1 mRNA (p < 0.01). LMWH promoted the proliferation, migration, and invasion of human decidual stromal cells; compared with the control group, the expression levels of MMP-2, MMP-7, cyclin D1, and PCNA proteins in the decidual stromal cells of the LMWH group increased (p < 0.05). CONCLUSIONS: The use of LMWH can improve pregnancy outcomes by enhancing the proliferation and migration of stromal cells in early pregnancy and the decidualization of stromal cells.


Assuntos
Aborto Habitual , Decídua , Gravidez , Humanos , Feminino , Animais , Camundongos , Heparina de Baixo Peso Molecular/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , Ciclina D1/metabolismo , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Células Estromais/metabolismo , Aborto Habitual/metabolismo , RNA Mensageiro/metabolismo
18.
Cancer ; 130(6): 973-984, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38018448

RESUMO

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. IKZF3 (IKAROS family zinc finger 3) is a hematopoietic-specific transcription factor, and it has been validated that it is involved in leukemia. However, the role of IKZF3 single-nucleotide polymorphisms (SNPs) remains unclear. In this case-control study, the authors investigated the association of IKZF3 SNPs with ALL in children. METHODS: Six IKZF3 reference SNPs (rs9635726, rs2060941, rs907092, rs12946510, rs1453559, and rs62066988) were genotyped in 692 patients who had ALL (cases) and in 926 controls. The associations between IKZF3 polymorphisms and ALL risk were determined using odds ratios (ORs) and 95% confidence intervals (CIs). The associations of rs9635726 and rs2060941 with the risk of ALL were further estimated by using false-positive report probability (FPRP) analysis. Functional analysis in silico was performed to evaluate the probability that rs9635726 and rs2060941 might influence the regulation of IKZF3. RESULTS: The authors observed that rs9635726C>T (adjusted OR, 1.49; 95% CI, 1.06-2.11; p = .023) and rs2060941G>T (adjusted OR, 1.51; 95% CI, 1.24-1.84; p = .001) were related to and increased risk of ALL in the recessive and dominant models, respectively. Furthermore, the associations of both rs9635726 (FPRP = .177) and rs2060941 (FPRP < .001) with ALL were noteworthy in the FPRP analysis. Functional analysis indicated that rs9635726 and rs2060941 might repress the transcription of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. CONCLUSIONS: This study revealed that IKZF3 polymorphisms were associated with increased ALL susceptibility in children and might influence the expression of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. IKZF3 polymorphisms were suggested as a biomarker for childhood ALL.


Assuntos
Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Estudos de Casos e Controles , Genótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Fator de Transcrição Ikaros/genética , Predisposição Genética para Doença
19.
Front Oncol ; 13: 1248280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023157

RESUMO

Background: In the field of minimally invasive surgery, the two-port laparoscopic surgery is on the rise. This study investigated the safety and efficacy of two-port laparoscopic surgery (TLS) for resecting sigmoid colon and upper rectal cancers compared with conventional laparoscopic surgery (CLS). Methods: The clinical data of patients undergoing laparoscopic sigmoid colon cancer and upper rectal cancer resection at the Department of General Surgery of the First Affiliated Hospital of Gannan Medical College between July 2019 and January 2022 were retrospectively collected. Grouped according to different laparoscopic surgery. Based on the inclusion and exclusion criteria,A total of 81 patients were enrolled, of the 25 patients from the TLS group,and of the 56 patients from the CLS group. We mainly compared whether there were statistical differences between the two groups in terms of operative time, intraoperative bleeding, incision length, time to first ambulation, time to first flatus, time to first defecation, postoperative complication rate, and other surgical outcomes. Results: There was no statistical difference between the two groups in terms of baseline clinical characteristics (P > 0.05). In terms of the surgical outcomes, there were statistical differences in the total incision length (TLS: 6.21 ± 0.67 cm, CLS: 8.64 ± 1.08 cm, P < 0.001)), time to first ambulation (TLS: 2.0 ± 0.7 d, CLS:3.1 ± 0.9 d, P < 0.001), time to first flatus (TLS: 2.5 ± 0.8 d, CLS: 3.0 ± 0.8 d, P = 0.028), time to first defecation (TLS: 3.8 ± 1.3 d, CLS: 5.1 ± 2.1 d, P = 0.010), and time for liquid diet (TLS: 4.3 ± 1.4 d, CLS: 5.3 ± 1.9 d, P = 0.021). There was no statistical difference between the two groups in terms of the pathology (P > 0.05). Conclusion: In terms of safety, TLS in sigmoid colon and upper rectal cancer resection is comparable to CLS. However, its incision is smaller and more aesthetic, and it causes lesser trauma than CLS. Additionally, it is also superior to CLS in postoperative recovery.

20.
Front Oncol ; 13: 1203002, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023199

RESUMO

Objective: PIWIL1 polymorphisms' role in pediatric acute lymphoblastic leukemia (ALL) relapse susceptibility remains undiscovered. Methods: A case-control designed and multiple logistic regression model was performed to evaluate the overall risk of pediatric ALL and five single-nucleotide polymorphisms (SNPs) of PIWIL1 gene (rs35997018 C>T, rs1106042 A>G, rs7957349 C>G, rs10773771 C>T, and rs10848087 A>G) in 785 cases and 1,323 controls, which were genotyped by TaqMan assay. The odds ratio (OR) and its 95% confidence interval (CI) were used to estimate the relationship. Stratified analysis was used to investigate the correlation of rs1106042 and rs10773771 genotypes and pediatric ALL relapse susceptibility in terms of age, sex, number of white blood cells (WBC), immunophenotyping, gene fusion type, karyotype, primitive/naïve lymphocytes, and minimal residual disease (MRD) in bone marrow. Finally, the haplotype analysis was performed to appraise the relationship between inferred haplotypes of PIWIL1 and pediatric ALL risk. Results: Among the five analyzed SNPs, rs1106042 A>G was related to increased ALL risk, and rs10773771 C>T was related to decreased ALL risk. Compared to the GG genotype, the rs1106042 GA/AA had a deleterious effect on children of age <120 months, who were female and male, had high or average number of WBC, pro-B ALL, pre-B ALL, T-ALL, low- and middle-risk ALL, E2A-PBX fusion gene, non-gene fusion, abnormal diploid, high hyperdiploid, hypodiploid, and normal diploid. Moreover, rs1106042 A>G harmfully affected primitive/naïve lymphocytes and MRD on days 15-19, day 33, and week 12. On the contrary, rs10773771 TC/CC exhibited a protective effect on ALL children with the TEL-AML fusion gene. Haplotype analysis demonstrated that haplotypes CAGT, TACC, TACT, and TAGT were significantly associated with increased pediatric ALL relapse susceptibility. Conclusion: PIWIL1 rs1106042 A>G was related to increased ALL risk, and rs10773771 C>T was linked to decreased ALL risk in eastern Chinese children. Rs1106042 GA/AA may predict poor prognosis.

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