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1.
Biochem Biophys Res Commun ; 734: 150633, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39243678

RESUMO

The study aimed to develop a prognostic model for Hepatocellular Carcinoma (HCC) based on pan-apoptosis-related genes, a novel inflammatory programmed cell death form intricately linked to HCC progression. Utilizing transcriptome sequencing and clinical data from the TCGA database, we identified six crucial pan-apoptosis-related genes through statistical analyses. These genes were then employed to construct a prognostic model that accurately predicts overall survival rates in HCC patients. Our findings revealed a strong correlation between the model's risk scores and tumor microenvironment (TME) status, immune cell infiltration, and immune checkpoint expression. Furthermore, we screened for drugs with potential therapeutic efficacy in high- and low-risk HCC groups. Notably, PPP2R5B gene knockdown was found to inhibit HCC cell proliferation and clonogenic capacity, suggesting its role in HCC progression. In conclusion, this study presents a novel pan-apoptosis gene-based prognostic risk model for HCC, providing valuable insights into patient TME status and guiding the selection of targeted therapies and immunotherapies.

2.
Food Res Int ; 192: 114850, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39147530

RESUMO

Rice has a long history as a staple food consumed by half of the world's population. Compared with white rice (WR), colored rice (CR) has more nutritional value because it contains rich active ingredients. In this study, the potential mechanism of CR (red rice (RR), green rice (GR), black rice (BR), and purple rice (PR)) for immunomodulation was explored by UPLC-Q-TOF, network pharmacology, and cell experiment. kuromanin, kaempferol-3-O-arabinoside, keracyanin, guajavarin, and hispidulin in CR were the critical components for improving immunity. These ingredients are mainly found in BR. Cell experiments supported that kuromanin plays a role in maintaining immune homeostasis. In the normal environment, it promotes cell proliferation and improves DNA repair; In an inflammatory environment, it binds to AKT1 and reduces the release of inflammatory factors through the MAPK and NFKB signaling pathways. The study provides a guideline for humans to utilize the precise nutrition of CR.


Assuntos
Farmacologia em Rede , Oryza , Oryza/química , Humanos , Cromatografia Líquida de Alta Pressão , Imunomodulação , Proliferação de Células/efeitos dos fármacos , Animais , Transdução de Sinais/efeitos dos fármacos
3.
Medicine (Baltimore) ; 103(29): e38844, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029005

RESUMO

The aim of this study is to assess alterations in heart function and structure in patients diagnosed with non-ST segment elevation acute myocardial infarction (NSTEAMI), unstable angina (UA), and stable angina (SA) 1 year after undergoing off-pump coronary artery bypass grafting (OPCABG) performed without extracorporeal circulation. A total of 182 patients who underwent OPCABG were included and classified into 3 groups based on their preoperative diagnosis: the NSTEAMI group (n = 68), the UA group (n = 64), and the SA group (n = 50). Cardiac ultrasonography data were collected for all groups both preoperatively and 1 year postoperatively. Clinical data were subjected to statistical analysis. In the NSTEAMI group, postoperative observations revealed increases in left ventricular stroke volume and left ventricular end-systolic diameter, along with reductions in left ventricular end-diastolic volume (LVEDV) and left ventricular end-diastolic diameter (LVEDD) 1-year post-surgery. The UA group demonstrated decreases in LVEDV and LVEDD 1-year post-surgery. Similarly, the SA group exhibited an increase in left ventricular ejection fraction (LVEF) and reductions in LVEDV and LVEDD 1-year post-surgery. Comparative analysis of cardiac ultrasonography data revealed that the NSTEAMI group displayed significantly lower left ventricular stroke volume and notably higher left ventricular end-systolic diameter and volume compared to the UA and SA groups 1-year post-surgery. Furthermore, the SA group exhibited significantly elevated LVEF compared to the UA and NSTEAMI groups 1-year post-surgery. Cardiac ultrasonography findings indicate that all 3 groups exhibited improvements in cardiac function and left ventricular structure 1-year post-surgery. However, the NSTEAMI group demonstrated more substantial improvements in comparison to the UA and SA groups.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Idoso , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Ecocardiografia/métodos , Angina Instável/cirurgia , Angina Instável/fisiopatologia , Angina Instável/diagnóstico por imagem , Angina Estável/cirurgia , Angina Estável/fisiopatologia , Angina Estável/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Ponte de Artéria Coronária/métodos
4.
Cancer Sci ; 115(8): 2617-2629, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38847328

RESUMO

Ubiquitin-specific peptidase 15 (USP15), a critical deubiquitinating enzyme, has been demonstrated to improve substrate stabilization by hydrolyzing the bond between the substrate and ubiquitin, and is implicated in multiple carcinogenic processes. Prompted by the information cited from The Cancer Genome Atlas (TCGA) database and the Cancer Proteogenomic Data Analysis Site (cProSite), USP15 is selectively overexpressed in clear cell renal cell carcinoma (ccRCC) samples. We aimed to investigate the function of USP15 on ccRCC malignant features, which was emphasized in its deubiquitination of SHC adaptor protein 1 (SHC1). The overexpression of USP15 promoted the capacity of proliferation, migration, and invasion in ccRCC CAKI1 and 769-P cells, and these malignant biological properties were diminished by USP15 deletion in 786-O cells. USP15 accelerated tumor growth and lung metastasis in vivo. In addition, deubiquitinase USP15 was further identified as a new protector for SHC1 from degradation by the ubiquitination pathway, the post-translational modification. In sequence, transcription factor activating enhancer binding protein 4 (TFAP4) was shown to be partly responsible for USP15 expression at the level of transcription, as manifested by the chromatin immunoprecipitation and pull-down assay. Based on the in vitro and in vivo data, we postulate that USP15 regulated by TFAP4 transcriptionally deteriorates ccRCC malignant biological properties via stabilizing SHC1 by deubiquitination.


Assuntos
Carcinoma de Células Renais , Proliferação de Células , Neoplasias Renais , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Proteases Específicas de Ubiquitina , Ubiquitinação , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Linhagem Celular Tumoral , Animais , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Camundongos , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Camundongos Nus , Masculino
5.
Sci Rep ; 14(1): 13834, 2024 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879709

RESUMO

Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the advancement of diverse malignancies. Nonetheless, the biological role and mechanisms of REEP3 in pancreatic cancer patients, along with its interplay with immune infiltration, remain inadequately elucidated. In this study, we initially analyzed the differential expression of REEP3 between pancreatic cancer tissues and normal pancreas tissues using the Cancer Genome Atlas (TCGA), GTEx and Gene Expression Omnibus (GEO) databases. Subsequently, we utilized Kaplan-Meier analysis, Cox regression and ROC curve to determine the predictive value of REEP3 for the clinical outcomes of pancreatic cancer patients. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), were conducted to explore the potential signaling pathways and biological functions associated with pancreatic cancer. Furthermore, we investigated the PPI network, miRNA, RBP and transcription factor interactions of REEP3 using databases such as GeneMania, STRING, StarBase, KnockTK, ENCODE, Jaspar and hTFtarget. Lastly, the "ssGSEA" algorithm and TIMER database were employed to investigate the correlation between REEP3 expression and immune infiltration as well as immune checkpoints. The expression of REEP3 in pancreatic cancer showed a significantly higher level compared to that in normal tissues. ROC curve analysis indicated that REEP3 holds substantial diagnostic potential for pancreatic cancer patients. Elevated REEP3 expression correlated with unfavorable outcomes in terms of both overall survival and relapse-free survival, establishing it as a notable adverse prognostic marker in pancreatic cancer. Moreover, both univariate and multivariate Cox regression analyses demonstrated that REEP3 maintained an independent association with overall survival. Functional enrichment analyses revealed pathways significantly linked to REEP3, including cytoplasmic translation, wound healing, viral processes, regulation of cellular component size and actin filament organization. Additionally, REEP3 expression displayed a significant positive correlation with CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. REEP3 is a potential diagnostic, prognostic marker and immunotherapeutic target for pancreatic cancer.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Mapas de Interação de Proteínas , Curva ROC
6.
Sensors (Basel) ; 24(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38610313

RESUMO

Simultaneous localisation and mapping (SLAM) is crucial in mobile robotics. Most visual SLAM systems assume that the environment is static. However, in real life, there are many dynamic objects, which affect the accuracy and robustness of these systems. To improve the performance of visual SLAM systems, this study proposes a dynamic visual SLAM (SEG-SLAM) system based on the orientated FAST and rotated BRIEF (ORB)-SLAM3 framework and you only look once (YOLO)v5 deep-learning method. First, based on the ORB-SLAM3 framework, the YOLOv5 deep-learning method is used to construct a fusion module for target detection and semantic segmentation. This module can effectively identify and extract prior information for obviously and potentially dynamic objects. Second, differentiated dynamic feature point rejection strategies are developed for different dynamic objects using the prior information, depth information, and epipolar geometry method. Thus, the localisation and mapping accuracy of the SEG-SLAM system is improved. Finally, the rejection results are fused with the depth information, and a static dense 3D mapping without dynamic objects is constructed using the Point Cloud Library. The SEG-SLAM system is evaluated using public TUM datasets and real-world scenarios. The proposed method is more accurate and robust than current dynamic visual SLAM algorithms.

7.
Asian J Surg ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38443248

RESUMO

The differences in the safety and efficacy of anticoagulation between different types of new oral anticoagulants(NOACs) and low molecular weight heparin(LMWH) are still controversial. The main purposes of this study were to analyze safety and efficacy of NOACs versus LMWH for thromboprophylaxis, and perform subgroup analyses stratified by individual NOACs and different populations after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Literature search was performed in PubMed, EMBASE, Cochrane Library, CNKI and Wanfang databases until June 31, 2022. This systematic review and meta-analysis included 46 randomized controlled trials (RCT) with 39, 924 patients. We evaluated the safety and efficacy of thromboprophylaxis between LMWH and NOACs. NOACs were more effective in reducing deep vein thrombosis (DVT) (RR0.59; 95%CI 0.49-0.71) and adverse events (RR: 0.96; 95%CI: 0.93-0.99) than LMWH. The subgroup analyses for different anticoagulants revealed that rivaroxaban (RR:0.49; 95%CI:0.36-0.66), apixaban (RR: 0.54; 95%CI: 0.36-0.81) and edoxaban (RR:0.49; 95%CI: 0.32-0.75) have the lower risk of DVT than LMWH. Apixaban (RR:0.89; 95%CI: 0.80-1.00) had superior prevention of bleeding to LMWH. Edoxaban exhibited a lower risk of VTE (RR: 0.46; 95%CI: 0.33-0.65), advantage events (RR: 0.87; 95%CI: 0.82-0.93), and drug-related adverse events (DRAEs) (RR: 0.64; 95%CI: 0.53-0.76) than LMWH. East Asian population was superior to western population for preventing DVT, advantage events, and DRAE using NOACs. In conclusion, NOACs are more effective than LMWH at preventing DVT and adverse events after arthroplasty. Apixaban has lower bleeding than LMWH, and East Asian populations may benefit more than western population from NOACs.

8.
Dalton Trans ; 53(5): 1977-1988, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38205595

RESUMO

Most platinum group-based cyclometalated neutral and cationic anticancer complexes with the general formula [(C^N)2Ir(XY)]0/+ (neutral complex: XY = bidentate anionic ligand; cationic complex: XY = bidentate neutral ligand) are notable owing to their intrinsic luminescence properties, good cell permeability, interaction with some biomolecular targets and unique mechanisms of action (MoAs). We herein synthesized a series of neutral and cationic amine-imine cyclometalated iridium(III) complexes using Schiff base ligands with sp2-N/sp3-N N^NH2 chelating donors. The cyclometalated iridium(III) complexes were identified by various techniques. They were stable in aqueous media, displayed moderate fluorescence and exhibited affinity toward bovine serum albumin (BSA). The complexes demonstrated promising cytotoxicity against lung cancer A549 cells, cisplatin-resistant lung cancer A549/DDP cells, cervical carcinoma HeLa cells and human liver carcinoma HepG2 cells, with IC50 values ranging from 9.98 to 19.63 µM. Unfortunately, these complexes had a low selectivity (selectivity index: 1.62-1.98) towards A549 cells and BEAS-2B normal cells. The charge pattern of the metal center (neutral or cationic) and ligand substituents showed little influence on the cytotoxicity and selectivity of these complexes. The study revealed that these complexes could target mitochondria, cause depolarization of the mitochondrial membrane, and trigger the production of intracellular ROS. Additionally, the complexes were observed to induce late apoptosis and perturb the cell cycle in the G2/M or S phase in A549 cells. Based on these results, it appears that the anticancer efficacy of these complexes was predominantly attributed to the redox mechanism.


Assuntos
Antineoplásicos , Carcinoma , Complexos de Coordenação , Neoplasias Pulmonares , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Células HeLa , Irídio/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/metabolismo , Ligantes , Quelantes/farmacologia , Mitocôndrias/metabolismo , Neoplasias Pulmonares/metabolismo , Carcinoma/metabolismo , Apoptose , Linhagem Celular Tumoral
9.
BMC Urol ; 24(1): 1, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166868

RESUMO

BACKGROUND: There are few studies on cryptorchidism in adults, and its treatment is still controversial. METHODS: To summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed. RESULTS: All testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach's triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery. CONCLUSION: Our study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient's reproductive hormone secretion function.


Assuntos
Criptorquidismo , Laparoscopia , Masculino , Humanos , Lactente , Criptorquidismo/cirurgia , Criptorquidismo/diagnóstico , Orquidopexia/métodos , Estudos Retrospectivos , Análise do Sêmen , Laparoscopia/métodos , Testículo , Resultado do Tratamento , Hormônios
10.
Environ Sci Pollut Res Int ; 31(3): 4269-4279, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38097840

RESUMO

Microbiologically influenced corrosion (MIC) is one of the reasons leading to the service failure of pipelines buried in the soil. In this work, the effect of sulfate-reducing bacteria (SRB) on the corrosion behavior of Q235 carbon steel in groundwater was investigated by electrochemical methods, surface analysis, and biological analysis. The results show that SRB utilizes iron as electron donor to sustain the vital activities of organic carbon-starved groundwater during the 14-day experimental period. The microbial community composition analysis at the genus level demonstrate that the diversity and richness decrease after corrosion, and the dominant SRB species has changed from Desulfovibrio to Desulfosporosinus. Moreover, the impedance of the carbon steel in the presence of biofilm was 1 order of magnitude higher than that of other periods in the electrochemical test, indicating that the biofilm and formed ferrous sulfide layer impeded the occurrence of corrosion. Although the 3D topography indicated that the surface of carbon steel was more uneven and pits were increased in the presence of SRB, the average weight loss (0.0396 ± 0.0050 g) was much higher than that without SRB (0.0139 ± 0.0007 g). These results implied that the growth of SRB makes the corrosion process of Q235 carbon steel more complicated.


Assuntos
Desulfovibrio , Água Subterrânea , Microbiota , Aço/química , Corrosão , Carbono/farmacologia , Biofilmes , Sulfatos/farmacologia
11.
Inorg Chem ; 62(51): 21379-21395, 2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38096360

RESUMO

The synthesis and biological evaluation of stable 16-electron half-sandwich complexes have remained scarce. We herein present the different coordination modes (16-electron or 18-electron) between half-sandwich iridium(III) complexes and ruthenium(II) complexes derived from the same amine-imine ligands chelating hybrid sp3-N/sp2-N donors. The 16-electron iridium(III) and 18-electron ruthenium(II) complexes with different counteranions were obtained and identified by various techniques. The promising cytotoxicity of these complexes against A549 lung cancer cells, cisplatin-resistant A549/DPP cells, cervical carcinoma HeLa cells, and human hepatocellular liver carcinoma HepG2 cells was observed with IC50 values ranging from 5.4 to 16.3 µM. Moreover, these complexes showed a certain selectivity (selectivity index: 2.1-3.7) toward A549 cells and BEAS-2B normal cells. The variation of metal center, counteranion, 16/18-electron coordination mode, and ligand substituents showed little influence on the cytotoxicity and selectivity of these complexes. The mechanism of action study showed that these complexes could target mitochondria, induce the depolarization of the mitochondrial membrane, and promote the generation of intracellular reactive oxygen species (ROS). Further, the induction of cell apoptosis and the perturbation of the cell cycle in the G0/G1 phase were also observed for these complexes. Overall, it seems that the redox mechanism dominated the anticancer efficacy of these complexes.


Assuntos
Antineoplásicos , Carcinoma , Complexos de Coordenação , Rutênio , Humanos , Antineoplásicos/farmacologia , Células HeLa , Iminas , Irídio/farmacologia , Rutênio/farmacologia , Complexos de Coordenação/farmacologia , Aminas/farmacologia , Ligantes , Elétrons , Apoptose , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo
12.
BMC Surg ; 23(1): 349, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974183

RESUMO

BACKGROUND: Laparoscopic pancreaticoduodenectomy(LPD) has become the goal of lots of minimally invasive surgical centers in recent years. Postoperative pancreatic fistula(POPF) is still the barrier to attaining the above goal. Thus, improving anastomosis techniques to reduce the rate of POPF has been a hotspot of surgery. Blumgart pancreaticojejunostomy is considered one of the best anastomosis procedures, with low rates of POPF. However, the original Blumgart pancreaticojejunostomy method is not easy for laparoscopic operation. In consequence, we modified a Blumgart pancreaticojejunostomy technique with a simple and practicable procedure and applied to LPD. METHODS: We collected and retrospectively analyzed the perioperative clinical data of patients who underwent modified Blumgart anastomosis from February 2017 to September 2022. The above patients included 53 cases in open pancreaticojejunostomy(OPD) and 58 cases in LPD. After propensity score matching, 44 cases were included for comparison in each group. RESULTS: After propensity score matching, the average time for pancreaticojejunostomy was about 30 min in the LPD group. The Clinically relevant POPF(CR-POPF) rate was 9.1%. The length of postoperative hospitalization was 13.1 days. Compared with the OPD group, The CR-POPF rate in the LPD group are not significant differences. But the postoperative length of hospital stay was significantly shorter in the LPD group. Besides, there were no other severely postoperative complications between two groups. CONCLUSION: The modified Blumgart anastomosis technique applied to LPD in our Center not only has simple and convenient properties but also low rate of CR-POPF. And this method may be a good choice for surgeons to begin to carry out LPD.


Assuntos
Laparoscopia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/métodos , Estudos Retrospectivos , Anastomose Cirúrgica/métodos , Pancreaticojejunostomia/métodos , Fístula Pancreática/etiologia , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia
13.
J Med Chem ; 66(21): 14633-14652, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37885208

RESUMO

Epidermal growth factor receptor (EGFR)-activating mutation is an important oncogenic driver of nonsmall cell lung cancer (NSCLC) patients. Osimertinib has been the first-line treatment for EGFR-mutated NSCLC. However, the tertiary C797S mutation leads to Osimertinib resistance by blocking the covalent binding of Cys797 to Osimertinib. To date, there are no approved inhibitors for the treatment of Osimertinib resistance. Herein, we identified a novel lead compound S8 targeting EGFRL858R/T790M/C797S by structure-based virtual screening and synthesized a series of novel compounds. Representative compound C34 showed potent inhibitory activity against EGFRL858R/T790M/C797S with an IC50 of 5.1 nM and significantly inhibited the proliferation of the H1975-TM cell line harboring EGFRL858R/T790M/C797S with an IC50 of 0.05 µM. Additionally, compound C34 demonstrated good pharmacokinetic properties with an oral bioavailability of 30.72% and significantly inhibited tumor growth in the H1975-TM xenograft tumor model. This study provides a novel thiazole derivative as an EGFR inhibitor to overcome C797S-mediated resistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/metabolismo , Receptores ErbB/metabolismo , Mutação , Resistencia a Medicamentos Antineoplásicos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/química , Compostos de Anilina/farmacologia , Linhagem Celular Tumoral
14.
Orthop Surg ; 15(12): 3279-3287, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37853985

RESUMO

OBJECTIVE: The Ward triangle is an important area used clinically to diagnose and assess osteoporosis and its fracture risk in the proximal femur. The main objective of this study was to investigate the rules of development and maturation of the trabeculae of Ward's triangle to provide a basis for the prevention and treatment proximal femur fracture. METHODS: From January 2018 to December 2019, individuals from 4 months to 19 years old who underwent hip growth and development assessments at the Third Hospital of Hebei Medical University were selected retrospectively. The outpatient electronic medical record system was used to collect information such as age, gender, imaging images, and clinical diagnosis. The development score and maturity characteristics of the trabecular bone were analyzed using hip radiograph data. Correlation analysis was performed to identify the relationship among age, neck-shaft angle and development and maturity score of the trabecular bone. RESULTS: A total of 941 patients were enrolled in this study, including 539 males and 402 females. Primary compression trabeculae were all present at 1 year of age and matured at 7 years of age and older; primary tension trabeculae were all present at 4 years of age and matured at 18 years of age. Secondary compression trabeculae were present at 4 years of age and matured at 18 years of age. In addition, the neck-shaft angle progressively decreases from 4 months to 14 years of age but barely changes between 15 and 19 years of age. CONCLUSION: In short, the development and maturation of the trabeculae in the ward' triangle followed a specific temporal pattern that was related to the neck-shaft angle. Therefore, these findings can help us understand structure and mechanical characteristics of proximal femoral trabeculae, and improve our understanding of the mechanism and treatment of proximal femoral fractures.


Assuntos
Osteoporose , Fraturas Proximais do Fêmur , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Densidade Óssea , Osso Esponjoso , Estudos Retrospectivos , Fêmur/diagnóstico por imagem
15.
Inorg Chem ; 62(37): 15118-15137, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37671819

RESUMO

The biological efficacy of half-sandwich platinum group organometallic complexes of the formula [(η5-Cpx)/(η6-arene)M(XY)Cl]0/+ (XY = bidentate ligands; Cpx = functionalized cyclopentadienyl; M = Ir, Rh, Ru, Os) has received considerable attention due to the significance of the metal center, chelating ligand, and Cpx/arene moieties in defining their anticancer potency and selectivity. With a facile access to the BIAN-derived imine-amine ligands using alkylaluminum as the reductant, we herein described the preparation and characterization of 16 half-sandwich Ir(III), Rh(III), and Ru(II) complexes chelating the hybrid sp2-N/sp3-N donor ligand. A nonplanar five-member metallacycle was confirmed by X-ray single-crystal structures of Ir1-Ir3, Ir7, Rh1, Ru1, and Ru4. The attempt to prepare imine-amido complexes using a base as the deprotonating agent led to the mixture of imine-amine complexes, within which the leaving group Cl- was displaced, and 16-electron imine-amido complexes without Cl-. The half-sandwich imine-amine complexes in this system underwent rapid hydrolysis in aqueous solution, exhibited weak photoluminescence, and showed the ability of binding to CT-DNA and BSA. The cytotoxicity of all imine-amine complexes against A549 lung cancer cell lines, HeLa cervical cancer cell lines, and 4T1 mouse breast cancer cells was determined by an MTT assay. The IC50 values of these complexes were in a range of 5.71-67.28 µM. Notably, most of these complexes displayed improved selectivity toward A549 cancer cells versus noncancerous BEAS-2B cells in comparison with the corresponding α-diimine complexes chelating the sp2-N/sp2-N donor ligand, which have been shown no selectivity in our previous report. The anticancer selectivity of these complexes appeared to be related to the redox-based mechanism including the catalytic oxidation of NADH to NAD+, reactive oxygen species (ROS) generation, and depolarization of the mitochondrial membrane. Further, inducing apoptosis of these complexes in A549 cancer cells and BEAS-2B normal cells also correlated with their anticancer selectivity, indicating the apoptosis mode of cell death in this system. In addition, these complexes could enter A549 cells via energy-dependent pathway and were able to impede the in vitro migration of A549 cells.


Assuntos
Ródio , Rutênio , Animais , Camundongos , Humanos , Ródio/farmacologia , Rutênio/farmacologia , Irídio/farmacologia , Ligantes , Aminas , Células HeLa
16.
BMC Genomics ; 24(1): 466, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596544

RESUMO

BACKGROUND: Plants possess mitochondrial genomes that are large and complex compared to animals. Despite their size, plant mitochondrial genomes do not contain significantly more genes than their animal counterparts. Studies into the sequence and structure of plant mitochondrial genomes heavily imply that the main mechanism driving replication of plant mtDNA, and offer valuable insights into plant evolution, energy production, and environmental adaptation. RESULTS: This study presents the first comprehensive analysis of Agrostis stolonifera's mitochondrial genome, characterized by a branched structure comprising three contiguous chromosomes, totaling 560,800 bp with a GC content of 44.07%. Annotations reveal 33 unique protein-coding genes (PCGs), 19 tRNA genes, and 3 rRNA genes. The predominant codons for alanine and glutamine are GCU and CAA, respectively, while cysteine and phenylalanine exhibit weaker codon usage biases. The mitogenome contains 73, 34, and 23 simple sequence repeats (SSRs) on chromosomes 1, 2, and 3, respectively. Chromosome 1 exhibits the most frequent A-repeat monomeric SSR, whereas chromosome 2 displays the most common U-repeat monomeric SSR. DNA transformation analysis identifies 48 homologous fragments between the mitogenome and chloroplast genome, representing 3.41% of the mitogenome's total length. The PREP suite detects 460 C-U RNA editing events across 33 mitochondrial PCGs, with the highest count in the ccmFn gene and the lowest in the rps7 gene. Phylogenetic analysis confirms A. stolonifera's placement within the Pooideae subfamily, showing a close relationship to Lolium perenne, consistent with the APG IV classification system. Numerous homologous co-linear blocks are observed in A. stolonifera's mitogenomes and those of related species, while certain regions lack homology. CONCLUSIONS: The unique features and complexities of the A. stolonifera mitochondrial genome, along with its similarities and differences to related species, provide valuable insights into plant evolution, energy production, and environmental adaptation. The findings from this study significantly contribute to the growing body of knowledge on plant mitochondrial genomes and their role in plant biology.


Assuntos
Agrostis , Genoma Mitocondrial , Animais , Uso do Códon , Filogenia , Edição de RNA
17.
Head Neck ; 45(9): 2161-2172, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37466293

RESUMO

BACKGROUND: Cysteine-rich protein 2 (CSRP2) is discovered as oncogene. The study aims to investigate the clinical significance and potential mechanism of CSRP2 in head and neck squamous cell carcinoma (HNSCC). METHODS: CSRP2 expression was explored by immunohistochemistry tissue microarrays and Western blotting in HNSCC. The effect of CSRP2 on the cancer stemness and epithelial-to-mesenchymal transition (EMT) of HNSCC cells was investigated by sphere formation, wound healing, and transwell assays. The vitro and vivo experiments revealed that CSRP2 modulated cancer stemness and EMT phenotypes in HNSCC. RESULTS: CSRP2 was overexpressed in HNSCC patients and presented poor prognosis. CSRP2 knockdown inhibited the migration and invasion ability of the HNSCC cells. And CSRP2 expression was closely associated with CSCs markers, EMT-transcription factor, new oncoprotein, and immune checkpoint. CONCLUSION: The overexpression of CSRP2 indicates poor prognosis and plays a key role in maintaining the cancer cell stemness and EMT.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/genética , Fatores de Transcrição/genética , Fenótipo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas Musculares/farmacologia , Proteínas Nucleares/genética , Proteínas com Domínio LIM/genética
18.
Mol Breed ; 43(7): 57, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37457120

RESUMO

In wheat, TaMYC8 is a negative regulator of cadmium (Cd)-responsive ethylene signaling. In this study, we functionally characterized TabHLH094, a basic helix-loop-helix (bHLH) transcription factor (TF) that inhibits the transcriptional activity of TaMYC8. The TabHLH094 protein was found in the nucleus of tobacco epidermal cells and exhibited transcriptional activation activity. Real-time quantitative PCR (RT-qPCR) indicated that TabHLH094 exhibited root-specific, Cd-responsive expression in wheat seedlings. Overexpression of TabHLH094 enhanced the tolerance of wheat seedlings to Cd exposure. The protein-protein interaction between TabHLH094 and TaMYC8 was verified by glutathione S-transferase (GST) pulldown, coimmunoprecipitation (Co-IP), yeast two-hybrid (Y2H), and bimolecular fluorescence complementation (BiFC) analyses. TabHLH094 was found to reduce the ability of TaMYC8 to bind to the TaERF6 promoter. Furthermore, TabHLH094 could also reduce aminocyclopropanecarboxylate oxidase (ACO) and ACC synthase (ACS) activities, both of which are necessary for ethylene biosynthesis. Taken together, these results indicate that TabHLH094 mediates Cd tolerance by regulating the transcriptional activity of TaMYC8 and decreasing ethylene production. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01404-1.

19.
J Health Popul Nutr ; 42(1): 73, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496103

RESUMO

BACKGROUND: Vitamin D deficiency is one of the most prevalent health problems worldwide in all age groups, whereas vitamin D status of Chinese college students was seldom studied in China. The purpose of this study was to explore the vitamin D status in Chinese college freshmen and its influencing factors, providing evidence for nutrition strategy application. METHODS: Information including demographic status, diet habit, physical activity, and ultraviolet ray (UV) protection was collected by online questionnaire. Serum 25(OH)D3 concentrations were measured using a liquid chromatograph mass spectrometer. Multivariate linear regression analyses were used to explore the comprehensive influence of diet, physical activity and UV protection on serum 25(OH)D3 levels. RESULTS: Totally 1667 freshmen from 26 provinces, autonomous districts or municipalities, were recruited, with a mean age of 18.6 ± 0.9 years. The mean serum 25(OH)D3 levels were 18.1 ± 6.3 ng/mL and the proportion of vitamin D deficiency and insufficiency was 67.5% and 27.8%, respectively. Multivariate linear regression indicated that higher intake of milk and yogurt, calcium or vitamin D supplementation, and longer time of outdoor activity were positively linked to higher serum 25(OH)D3, while higher intake of candy and higher UV protection index were negatively associated with serum 25(OH)D3, after adjusted for age, gender, region of original residence, latitudes, longitude and BMI. CONCLUSIONS: Vitamin D deficiency is very common in Chinese college students. Milk and yogurt intake and outdoor activity should be encouraged while candy intake should be limited for preventing vitamin D deficiency. Public health policies should focus on these changeable lifestyles and consider well-balanced guidelines on UV protection and vitamin D supplementation.


Assuntos
Deficiência de Vitamina D , Vitamina D , Humanos , Adolescente , Adulto Jovem , Adulto , Dieta , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/prevenção & controle , Exercício Físico , Estudantes , Suplementos Nutricionais
20.
Environ Sci Technol ; 57(29): 10882-10890, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37436147

RESUMO

Gaseous elemental mercury (Hg0) extraction from industrial flue gases is undergoing intense research due to its unique properties. Selective adsorption that renders Hg0 to HgO or HgS over metal oxide- or sulfide-based sorbents is a promising method, yet the sorbents are easily poisoned by sulfur dioxide (SO2) and H2O vapor. The Se-Cl intermediate derived from SeO2 and HCl driven by SO2 has been demonstrated to stabilize Hg0. Thus, a surface-induced method was put forward when using γ-Al2O3 supported selenite-chloride (xSeO32--yCl-, named xSe-yCl) for mercury deposition. Results confirmed that under 3000 ppm SO2 and 4% H2O, Se-2Cl exhibited the highest induced adsorption performance at 160 °C and higher humidity can accelerate the induction process. Driven by SO2 under the wet interface, the in situ generated active Se0 has high affinity toward Hg0, and the introduction of Cl- enabled the fast-trapping and stabilization of Hg0 due to its intercalation in the HgSe product. Additionally, the long-time scale-up experiment showed a gradient color change of the Se-2Cl-induced surface, which maintained almost 100% Hg0 removal efficiency over 180 h with a normalized adsorption capacity of 157.26 mg/g. This surface-induced method has the potential for practical application and offers a guideline for reversing the negative effect of SO2 on gaseous pollutant removal.


Assuntos
Poluentes Atmosféricos , Poluentes Ambientais , Mercúrio , Dióxido de Enxofre , Mercúrio/análise , Cloretos , Óxidos , Adsorção , Poluentes Atmosféricos/análise
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