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1.
Artigo em Inglês | MEDLINE | ID: mdl-38578592

RESUMO

Facing the increasingly stringent constraints of resources and the environment, the green transformation of enterprises is imperative. This study selects A-share listed companies in Shanghai and Shenzhen from 2014 to 2021 as samples, using the difference-in-differences method to examine the impact of the environmental protection tax reform (EPTR) on the green transformation of enterprises. The results indicate that the EPTR can promote the green transformation of enterprises, achieving this through three channels: raising the cost of pollution, strengthening the rigidity of law enforcement, and breaking the collusion between the government and enterprises. Notably, this promotional effect is more significant in non-state-owned enterprises, companies in the eastern and western regions, firms with low financing constraints, and those with high media attention. Further analysis shows that the EPTR has a positive impact on the green total factor productivity (GTFP) of enterprises, which implies that enterprises are not only proactively pushing for a green transformation at the strategic level but also taking practical actions. This study responds to the problem of the greening of tax system to promote the green development of enterprises from two aspects of enterprise strategic implementation and productivity and explores the impact mechanism from the perspective of institutional logic. It enriches the research on the effectiveness of the EPTR at the micro-level and broadens the research perspective on the impact mechanisms of environmental regulation. The findings of this study provide references for further optimising relevant policies and regulations and also offer insights for other countries and regions seeking sustainable development.

2.
Food Chem ; 447: 138915, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38452539

RESUMO

Peanuts, sourced from various regions, exhibit noticeable differences in quality owing to the impact of their natural environments. This study proposes a fast and nondestructive detection method to identify peanut quality by combining an electronic nose system with a hyperspectral system. First, the electronic nose and hyperspectral systems are used to gather gas and spectral information from peanuts. Second, a module for extracting gas and spectral information is designed, combining the lightweight multi-head transposed attention mechanism (LMTA) and convolutional computation. The fusion of gas and spectral information is achieved through matrix combination and lightweight convolution. A hybrid neural network, named UnitFormer, is designed based on the information extraction and fusion processes. UnitFormer demonstrates an accuracy of 99.06 %, a precision of 99.12 %, and a recall of 99.05 %. In conclusion, UnitFormer effectively distinguishes quality differences among peanuts from various regions, offering an effective technological solution for quality supervision in the food market.


Assuntos
Arachis , Nariz Eletrônico , Meio Ambiente , Alimentos , Redes Neurais de Computação
3.
J Colloid Interface Sci ; 665: 564-572, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38552573

RESUMO

Rechargeable aqueous zinc ion batteries (ZIBs) have emerged as a promising alternative to lithium-ion batteries due to their inherent safety, abundant availability, environmental friendliness and cost-effectiveness. However, the cathodes in ZIBs encounter challenges such as structural instability, low capacity, and sluggish kinetics. In this study, we constructed BiVO4@VO2 (BVO@VO) heterojunction cathode material with bismuth vanadate and vanadium dioxide phases for ZIBs, which demonstrate significant advancements in both aqueous and quasi-solid-state ZIBs. Benefitting from the heterojunction structure, the materials present a high capacity of 262 mAh g-1 at 0.1 A g-1, superb cyclic stability with 96% capacity retention after 1000 cycles at 2 A g-1, and outstanding rate property with a specific capacity of 218 mAh g-1 even at a high rate of 5.0 A g-1. Furthermore, the flexible quasi-solid-state ZIBs incorporating the BVO@VO cathode demonstrate prolonged cyclic life performance with a remarkable specific capacity of 234 mAh g-1 over 100 cycles at a current density of 0.1 A g-1. This study potentially paves the way for the utilization of heterointerface-enhanced zinc ion diffusion for vanadium-based materials in ZIBs, thereby providing a new approach for the design and investigation of high-performance zinc-ion systems.

4.
J Biochem Mol Toxicol ; 38(2): e23659, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348706

RESUMO

Circ_0081069 plays a key role in tumor growth; however, its effect on radiosensitivity in esophageal squamous cell carcinoma (ESCC) remains unknown. The study is performed to reveal the association of circ_0081069 expression and radiosensitivity in ESCC and the underlying mechanism. Circ_0081069, miR-195-5p, and spindlin 1 (SPIN1) RNA expression were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell viability, proliferation, cell apoptosis, migration, and invasion were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, scratch test, and transwell assays, respectively. The sensitivity of ESCC cells to radiation was investigated by cell colony formation assay. The interactions among circ_0081069, miR-195-5p, and SPIN1 were identified by dual-luciferase reporter assay and RNA Immunoprecipitation assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on radiosensitivity in vivo. Circ_0081069 and SPIN1 expression were upregulated, whereas miR-195-5p was downregulated in ESCC tissues, ESCC cells, and radiation-stimulated ESCC cells. Circ_0081069 silencing inhibited ESCC cell proliferation, invasion, and migration but improved cell apoptosis. In addition, circ_0081069 knockdown enhanced ESCC cell radiosensitivity in vitro and in vivo. Circ_0081069 bound to miR-195-5p and regulated radiosensitivity by binding to miR-195-5p in ESCC cells. Moreover, SPIN1, a target of miR-195-5p, rescued miR-195-5p-mediated effects in ESCC cells. Circ_0081069 was secreted from ESCC cells by being packaged into exosomes. Further, circ_0081069-Exo inhibited radiosensitivity in ESCC cells. Exosome-mediated transfer of circ_0081069 induced SPIN1 production by binding to miR-195-5p, further inhibiting radiosensitivity in ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Exossomos , MicroRNAs , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/radioterapia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Transporte Biológico , Modelos Animais de Doenças , MicroRNAs/genética , Proliferação de Células , Linhagem Celular Tumoral
5.
Curr Med Chem ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38375846

RESUMO

Previous studies described that asthma patients who received corticosteroid therapy have been constrained by the corticosteroid resistance subsequently fostered to severe refractory asthma. In this review, we discussed the implications of TSLP, RXR, the role of STAT5-activating cytokines, and IL-33/NH-cell signaling pathways, and recent clinical evidence on TSLP blockers in steroid-resistant asthma. We have searched several public databases such as Pubmed, Scopus, and Relemed and obtained information pertinent to the TSLP, RXR, TSLP blockers, the STAT5-activating cytokines, and IL-33. We discussed the multiple cell signaling mechanisms underlying steroid resistance. Blocking the TSLP and other key signaling molecules like STAT5 can retrieve the sensitivity of natural helper-cells to corticosteroids. RXR derivatives treatment can modulate the activity of TSLP, which further modulates steroid resistance in severe asthmatic patients and in patients with refractory asthma. We discussed the steroid-resistance mediated by the Th2 cells and Th2-driven eosinophilia upon corticosteroid intake. Thus, this review will be beneficial for clinicians and molecular biologists to explore the inflammatory pathways associated with refractory asthma conditions and develop novel therapies against corticosteroid-resistant asthma.

6.
Toxicol Ind Health ; 40(4): 176-184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38349948

RESUMO

A rapid and sensitive assessment of the toxicity of oxygenated polycyclic aromatic hydrocarbons (OPAHs), widely distributed persistent organic pollutants in the environment, is crucial for human health. In this study, using high-performance liquid chromatography, the separation and detection of four purines, xanthine (X), guanine (G), adenine (A), and hypoxanthine (HX) in cells were performed. The aim was to evaluate the cytotoxicity of three OPAHs, namely 1,4-benzoquinone (1,4-BQ), 1,2-naphthoquinone (1,2-NQ) and 9,10-phenanthrenequinone (9,10-PQ), with higher environmental concentrations, from the perspective of purine nucleotide metabolism in human skin fibroblast cells (HFF-1). The results revealed that the levels of G and A were low in HFF-1 cells, while the levels of HX and X showed a dose-response relationship with persistent organic pollutants concentration. With increased concentration of the three persistent organic pollutants, the purine metabolism in HFF-1 cells weakened, and the impact of the three persistent organic pollutants on purine metabolism in cells was in the order of 9,10-PQ > 1,4-BQ > 1,2-NQ. This study provided valuable insights into the toxic mechanisms of 1,4-BQ, 1,2-NQ and 9,10-PQ, contributing to the formulation of relevant protective measures and the safeguarding of human health.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Orgânicos Persistentes , Cromatografia Líquida de Alta Pressão/métodos , Purinas/análise , Fibroblastos/química
7.
Curr Med Chem ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38299393

RESUMO

BACKGROUND: Gliomas and glioblastomas (GBM) are common primary malignant brain tumors, which are highly malignant and have a poor prognosis. The presence of cancer stem cells with unrestricted proliferative capacity and ability to generate glial neoplastic cells, the diffuse nature of GBM, and other specific factors of GBM contribute to poor results of drug therapy in patients with GBM. Despite the worldwide efforts to improve the treatment, many novel anti-GBM drugs are active just in vitro, in silico, and in preclinical trials, and they sometimes demonstrate poor or no activity in clinical trials. In this paper, we have casually selected and analyzed the most promising evidence-based results related to glioblastoma treatment at FDA and Clinical Trials.gov databases. It was observed that the most prospective trend in the development of anti-GBM drugs is combination therapy vs. monotherapy. Our analysis of clinical trials has allowed us to predict that the most promising combination therapy that has shown the best results in patient's surveillance should include drugs that block different growth-promoting signals in glioblastoma cells and that are activated by the V600E BRAF mutation. One drug should inhibit signals from the BRAF protein, whereas the second drug in combination should inhibit signals from the MEK protein Methods: The content of this review is based on information obtained from PubMed, ClinicalTrials. gov, and the U.S. Food and Drug Administration (https://www.fda.gov/). In ClinicalTrials.gov, we retrieved studies published from January 1, 2015. In the data search, "Glioblastoma" was used as the keyword. A study was deleted if it studied remedies for concomitant tumor diseases, as well as if it did not include descriptions of treatment methods and/or if GBM was not mentioned. The analysis of the effectiveness of treatment was carried out according to the increasing overall survival in GBM patients, compared to the gold standard for this cancer. RESULTS: GBM patients treated with novel immunotherapy agents and drugs acting on epigenetic factors and receptor tyrosine kinase inhibitors have shown encouraging potential for future development in clinic. However, combinations of drugs have led to more significant improvements in the results and an increase in life expectancy of patients. For example, the combination of nivolumab and ipilimumab showed a 72% increase in life expectancy compared to using nivolumab alone (9.8 vs. 16.85). CONCLUSION: Combining anti-GBM drugs appears to be a key direction for increasing treatment effectiveness and overall survival. Radiotherapy of GBM can increase the effect of combination drug therapy.

8.
Curr Med Chem ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38243981

RESUMO

BACKGROUND: Glyphosate-based herbicide (GBH) formulations are organophosphorus pesticides implicated for agricultural use. Several epidemiological reports have reported that the occupational exposure of farmers to glyphosate can cause age-related neurodegeneration. OBJECTIVE: the objective of this study is to examine the neurotoxic effects of glyphosate and its intricate role in triggering several neurodegenerative diseases like dementia, nootropic defects, Parkinson's disease, and neurological teratogenic effects due to its negative effects on the nervous system. Furthermore, the efficacy of phytochemicals against glyphosate-induced neurotoxicity was discussed. METHODS: We have searched public databases such as NLM, Pubmed, google scholar and collected a total of 103 articles including reviews, original articles, and obtained information related to glyphosate-induced neurotoxicity and novel phytochemicals implicated to ameliorate the glyphosate-induced neurotoxicity. We performed a systematic review without comprehensive meta-analysis. RESULTS: the efficacy of several phytochemicals as a nutritional intervention against glyphosate-induced neurotoxicity including Parkinsonism was elucidated by vivid review analysis of neurobehavioral alterations from in vitro and in vivo study models. CONCLUSION: These kinds of research projects will bring awareness about the neurotoxic effects of glyphosate and the protective nutritional intervention strategies against glyphosate-induced neurotoxicity including Parkinsonism for farmers.

9.
J Cancer ; 15(1): 149-165, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164283

RESUMO

This study was aimed to investigate the prognostic value and clinical significance of sarcosine dehydrogenase (SARDH) in hepatocellular carcinoma (HCC) and to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), HPA and CPTAC databases were adopted to analyze the expression of SARDH mRNA and protein between normal liver tissue and HCC, and examine their relationship with clinicopathological features. Kaplan-Meier analysis, Cox regression, as well as nomogram were adopted to explore the prognostic value of SARDH in HCC. Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) together with Gene Set Enrichment Analysis (GSEA) were adopted to analyze the molecular mechanisms and biological functions of SARDH in HCC; while MethSurv, STRING, GeneMANIA, TIMER database data and single-sample gene set enrichment analysis (ssGSEA) algorithm were used for other bioinformatic analysis. Furthermore, immunohistochemistry was used to verify the expression of SARDH. Compared to normal liver tissue, SARDH expression was markedly lower in HCC. A lower SARDH expression was linked with Pathologic T stage (T3&T4), pathologic stage (Stage III&IV), and histologic grade (G3&4), which further indicates worse prognosis. Besides, results of bioinformatic analysis proved that SARDH expression was correlated with immune infiltration. In addition, SARDH hypermethylation was related to a poorer prognosis. SARDH expression was related to several key genes in the Ferroptosis pathway.

10.
World Neurosurg ; 181: e493-e503, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37898275

RESUMO

BACKGROUND: To assist doctors in making better treatment decisions and improve patient prognosis, it is important to determine which therapy modalities are suitable for various forms of idiopathic hypertrophic cranial pachymeningitis (IHCP). METHODS: All cases were received from the hospital medical record system, and some follow-up information was gathered through telephone follow-up. RESULTS: A total of 26 patients, 14 men and 12 women, with ages ranging from 20 to 73 years and a mean of 47.42 years, were included in the research. Regular types were less likely to recur than irregular and nodular types, focal types were less likely to recur than diffuse types, and corticosteroid-refractory types were more likely to recur than corticosteroid-sensitive types. CONCLUSIONS: The extent and shape of the lesion and susceptibility to corticosteroids are potential factors that could influence recurrence. Futhermore, this paper also proposes the fibroblasts as a new therapeutic target which may improve the quality of prognostic survival of patients.


Assuntos
Meningite , Masculino , Humanos , Feminino , Meningite/patologia , Corticosteroides/uso terapêutico , Tomada de Decisões , Fibroblastos/patologia , Hipertrofia/patologia , Imageamento por Ressonância Magnética , Dura-Máter/patologia
11.
Oncologist ; 29(2): e275-e281, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-37874925

RESUMO

BACKGROUND: Retinoblastoma is the most common intraocular malignant tumor occurring among children, with an incidence rate of 1/15 000. This study built a joinpoint regression model to assess the incidence trend of retinoblastoma from 2004 to 2015 and constructed a nomogram to predict the overall survival (OS) in children. MATERIALS AND METHODS: Patients less than 19 years diagnosed with retinoblastoma from 2004 to 2015 were selected from the SEER database. Joinpoint regression analysis (version 4.9.0.0) was performed to evaluate the trends in retinoblastoma incidence rates from 2004 to 2015. Cox Regression Analysis was applied to investigate prognostic risk factors that influence OS. RESULTS: Joinpoint regression revealed that retinoblastoma incidence exhibited no significant increase or decrease from 2004 to 2015. As per the multiple Cox regression, tumor size, laterality, and residence (rural-urban continuum code) were correlated with OS and were used to construct a nomogram. The nomogram exhibited a good C-index of 0.71 (95% CI, 0.63 to 0.79), and the calibration curve for survival probability demonstrated that the predictions corresponded well with actual observations. CONCLUSIONS AND RELEVANCE: A prognostic nomogram integrating the risk factors for retinoblastoma was constructed to provide comparatively accurate individual survival predictions. If validated, this type of assessment could be used to guide therapy in patients with retinoblastoma.


Assuntos
Neoplasias da Retina , Retinoblastoma , Criança , Humanos , Prognóstico , Nomogramas , Incidência , Retinoblastoma/epidemiologia , Neoplasias da Retina/epidemiologia , Programa de SEER
12.
Phys Med Biol ; 69(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38086076

RESUMO

Objective. Convolutional neural networks (CNNs) have made significant progress in medical image segmentation tasks. However, for complex segmentation tasks, CNNs lack the ability to establish long-distance relationships, resulting in poor segmentation performance. The characteristics of intra-class diversity and inter-class similarity in images increase the difficulty of segmentation. Additionally, some focus areas exhibit a scattered distribution, making segmentation even more challenging.Approach. Therefore, this work proposed a new Transformer model, FTransConv, to address the issues of inter-class similarity, intra-class diversity, and scattered distribution in medical image segmentation tasks. To achieve this, three Transformer-CNN modules were designed to extract global and local information, and a full-scale squeeze-excitation module was proposed in the decoder using the idea of full-scale connections.Main results. Without any pre-training, this work verified the effectiveness of FTransConv on three public COVID-19 CT datasets and MoNuSeg. Experiments have shown that FTransConv, which has only 26.98M parameters, outperformed other state-of-the-art models, such as Swin-Unet, TransAttUnet, UCTransNet, LeViT-UNet, TransUNet, UTNet, and SAUNet++. This model achieved the best segmentation performance with a DSC of 83.22% in COVID-19 datasets and 79.47% in MoNuSeg.Significance. This work demonstrated that our method provides a promising solution for regions with high inter-class similarity, intra-class diversity and scatter distribution in image segmentation.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico por imagem , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador
13.
Am J Orthod Dentofacial Orthop ; 165(3): 272-284.e3, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38108674

RESUMO

INTRODUCTION: Clear aligners (CAs) have recently become popular and widely used orthodontic appliances. Research on CA biomechanics has become a focal point in orthodontics to improve the efficiency of CA treatment and address challenging issues, such as extraction. The biomechanical characteristics of CAs in space closure have been reported. However, previous studies have mainly focused on static biomechanical analysis that cannot demonstrate the dynamic biomechanical changes in CAs during space-closing. Given that these biomechanical changes can be significant and have considerable clinical value, this study aimed to investigate these characteristics. METHODS: Sequential extraction space-closing models were derived from included patient data and refined using modeling and CA design software. A finite element analysis was performed to obtain biomechanical raw data. This study introduced a dual coordinate system and space geometry analysis to demonstrate the biomechanical properties accurately. RESULTS: As space closure progressed, the instantaneous tooth displacements increased, indicating an enhanced space closure force because of the increased strain in the CA extraction area. Meanwhile, the central axis of rotation of the anterior teeth continuously moved toward the labial-apical direction, showing a gradually enhanced vertical and torque control effect. CONCLUSIONS: During space closure, CAs undergo specific biomechanical changes, including increased contraction and control forces on both sides of the gap. These biomechanical effects are beneficial to alleviate the roller coaster effect gradually. Meanwhile, more reasonable staging design strategies can be proposed on the basis of this biomechanical mechanism.


Assuntos
Aparelhos Ortodônticos Removíveis , Técnicas de Movimentação Dentária , Humanos , Análise de Elementos Finitos , Incisivo , Aparelhos Ortodônticos , Fenômenos Biomecânicos
14.
Artigo em Inglês | MEDLINE | ID: mdl-38103500

RESUMO

Intermuscular bones (IBs) are mineralized spicules that negatively impact the quality and value of fish products. Runx2b is a crucial modulator in promoting bone formation through regulating osteoblast differentiation. Previous studies suggested that loss of runx2b gene completely inhibited IBs formation in zebrafish. However, how the whole transcriptome, including mRNA and non-coding RNA (ncRNA), affects the IBs development in runx2b-/- zebrafish are not known. The aim of this study was to identify the regulatory networks of differentially expressed (DE) lncRNAs, miRNAs, and mRNAs in zebrafish with and without IBs (runx2b+/+ fish and runx2b-/- fish) utilizing high-throughput sequencing techniques. All together there are 1051 mRNAs, 456 lncRNAs, and 18 miRNAs differentially expressed were found between these two strains. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) has highlighted significant pathways linked to the development of IBs, specifically the TGF-beta and Wnt signaling pathways, and a number of genes concentrated on these two signaling pathways related to the formation of IBs. Further, 1989 competing endogenous RNA (ceRNA) networks were created according to the correlation among mRNAs, miRNAs and lncRNAs. The ceRNA networks results revealed 52 ceRNA pairs related to the IBs formation, consisting of 52 mRNAs, 37 lncRNAs, and 6 miRNAs. Of these, we found that dre-miR-2189 was the key element of ceRNA pairs, interacting with 19 mRNAs and 11 lncRNAs, and MSTRG.13175.1 could regulate sp7 expression by interacting with dre-miR-2189 to function in osteogenic differentiation. Subsequent experiments at the cellular level also revealed the interaction mechanism. The outcomes indicated a crucial role of miRNAs and lncRNAs in the development of fish IBs, which offer new views into the functions of ncRNAs involved in IBs formation.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Redes Reguladoras de Genes , MicroRNAs/genética , Osteogênese/genética , 60414 , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
15.
Opt Express ; 31(25): 42677-42686, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38087636

RESUMO

Microresonator-based high-speed single-mode quantum cascade lasers are ideal candidates for on-chip optical data interconnection and high sensitivity gas sensing in the mid-infrared spectral range. In this paper, we propose a high frequency operation of single-mode doughnut-shaped microcavity quantum cascade laser at ∼4.6 µm. By leveraging compact micro-ring resonators and integrating with grounded coplanar waveguide transmission lines, we have greatly reduced the parasitics originating from both the device and wire bonding. In addition, a selective heat dissipation scheme was introduced to improve the thermal characteristics of the device by semi-insulating InP infill regrowth. The highest continuous wave operating temperature of the device reaches 288 K. A maximum -3 dB bandwidth of 11 GHz and a cut-off frequency exceeding 20 GHz in a microwave rectification technique are obtained. Benefiting from the notch at the short axis of the microcavity resonator, a highly customized far-field profile with an in-plane beam divergence angle of 2.4° is achieved.

16.
PLoS One ; 18(11): e0283705, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37910519

RESUMO

Fructosamine-3-kinase (FN3K) is involved in the deglycation of Nrf2, a significant regulator of oxidative stress in cancer cells. However, the intricate functional aspects of FN3K and Nrf2 in breast cancers have not been explored vividly. The objectives of this study are to design the human FN3K protein using homology modeling followed by the screening of several anticancer molecules and examining their efficacy to modulate FN3K activity, Nrf2-mediated antioxidant signalling. Methods pertinent to homology modeling, virtual screening, molecular docking, molecular dynamics simulations, assessment of ADME properties, cytotoxicity assays for anticancer molecules of natural/synthetic origin in breast cancer cells (BT-474, T-47D), and Western blotting were used in this study. The screened anticancer molecules including kinase inhibitors of natural and synthetic origin interacted with the 3-dimensional structure of the catalytic domain in human FN3K protein designed through homology modeling by significant CDOCKER interaction energies. Subsequently, gefitinib, sorafenib, neratinib, tamoxifen citrate, and cyclosporine A enhanced the expression of FN3K in BT-474 cell lines with simultaneous alteration in Nrf2-driven antioxidant signalling. Oxaliplatin significantly downregulated FN3K expression and modulated Nrf2-driven antioxidant signalling when compared to cisplatin and other anticancer drugs. Hence, the study concluded the potential implications of existing anticancer drugs to modulate FN3K activity in breast cancers.


Assuntos
Antineoplásicos , Fator 2 Relacionado a NF-E2 , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Simulação de Dinâmica Molecular , Antioxidantes , Simulação de Acoplamento Molecular , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Antineoplásicos/farmacologia
17.
Curr Pharm Des ; 29(34): 2738-2751, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37916622

RESUMO

INTRODUCTION: Dose reconstructed based on linear accelerator (linac) log-files is one of the widely used solutions to perform patient-specific quality assurance (QA). However, it has a drawback that the accuracy of log-file is highly dependent on the linac calibration. The objective of the current study is to represent a new practical approach for a patient-specific QA during Volumetric modulated arc therapy (VMAT) using both log-file and calibration errors of linac. METHODS: A total of six cases, including two head and neck neoplasms, two lung cancers, and two rectal carcinomas, were selected. The VMAT-based delivery was optimized by the TPS of Pinnacle^3 subsequently, using Elekta Synergy VMAT linac (Elekta Oncology Systems, Crawley, UK), which was equipped with 80 Multi-leaf collimators (MLCs) and the energy of the ray selected at 6 MV. Clinical mode log-file of this linac was used in this study. A series of test fields validate the accuracy of log-file. Then, six plans of test cases were delivered and log-file of each was obtained. The log-file errors were added to the corresponding plans through the house script and the first reconstructed plan was obtained. Later, a series of tests were performed to evaluate the major calibration errors of the linac (dose-rate, gantry angle, MLC leaf position) and the errors were added to the first reconstruction plan to generate the second reconstruction plan. At last, all plans were imported to Pinnacle and recalculated dose distribution on patient CT and ArcCheck phantom (SUN Nuclear). For the former, both target and OAR dose differences between them were compared. For the latter, γ was evaluated by ArcCheck, and subsequently, the surface dose differences between them were performed. RESULTS: Accuracy of log-file was validated. If error recordings in the log file were only considered, there were four arcs whose proportion of control points with gantry angle errors more than ± 1°larger than 35%. Errors of leaves within ± 0.5 mm were 95% for all arcs. The distinctness of a single control point MU was bigger, but the distinctness of cumulative MU was smaller. The maximum, minimum, and mean doses for all targets were distributed between -6.79E-02-0.42%, -0.38-0.4%, 2.69E-02-8.54E-02% respectively, whereas for all OAR, the maximum and mean dose were distributed between -1.16-2.51%, -1.21-3.12% respectively. For the second reconstructed dose: the maximum, minimum, and mean dose for all targets was distributed between 0.0995~5.7145%, 0.6892~4.4727%, 0.5829~1.8931% separately. Due to OAR, maximum and mean dose distribution was observed between -3.1462~6.8920%, -6.9899~1.9316%, respectively. CONCLUSION: Patient-specific QA based on the log-file could reflect the accuracy of the linac execution plan, which usually has a small influence on dose delivery. When the linac calibration errors were considered, the reconstructed dose was closer to the actual delivery and the developed method was accurate and practical.


Assuntos
Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Calibragem , Garantia da Qualidade dos Cuidados de Saúde/métodos
18.
Curr Med Chem ; 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38018189

RESUMO

BACKGROUND: Chemoresistance by stemness in HPV-induced cervical carcinogenesis has significant implications for the overall disease-specific survival of the patients. To date, there are no reports related to the implications of significant aspects of inflammation and microbiome-- mediated epigenetics in cervical cancers. OBJECTIVE: The current systematic review delineates the significant aspects of the inflammation-related pathophysiology, cervical cancer diagnosis based on the HPV-indued stemness, and microbiome- mediated epigenetic markers to develop personalized therapies to target the stemness-acquired indefinitely dividing cancer stem cells. METHODS: We performed a systematic review without a meta- analysis. We searched several public databases, such as Pubmed, ReleMed, National Library of Medicine, and Scopus, related to inflammation, metabolomics, microbiome-mediated epigenetic markers, and HPV-induced stemness. RESULTS AND CONCLUSION: The review significantly described the correlation between microbial inflammation and stem cell stochasticity of HPV-Induced cervical cancer and the expression of epigenetics- based biomarkers through microbiome and metabolome to foster the cervical cancer progression. These are major risk factors that can cause cervical dysplasia with substantial therapy resistance in cervical cancer patients. The qualitative and quantitative examination of the spatial transcriptomic expression of these stemness markers in the dividing cervical cancer stem cells has significant implications in the clinical sector to develop early personalized medicine to prevent cervical precancerous lesions depending on the prognosis of the cervical cancer patients. Mainly, the combinatorial regimen of current therapeutic modalities, along with microbiome-related therapies with future landscape of epigenetics-modulated therapies, may enhance overall disease-specific survival by modulating the stochastic dynamics of basal epithelial cells across the cervical region.

19.
Curr Med Chem ; 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38018190

RESUMO

Conventional therapeutic modalities against the cancers such as surgery, chemotherapy (CT) and radiotherapy (RT) have limited efficacy due to drug resistance, and adverse effects. Recent developments in nanoscience emphasized novel approaches to overcome the aforementioned limitations and subsequently improve overall clinical outcomes in cancer patients. Photodynamic therapy (PDT), photothermal therapy (PTT), and radiodynamic therapy (RDT) can be used as cancer treatments due to their high selectivity, low drug resistance, and low toxicity. Mitocans are the therapeutic molecules that can produce anti-cancer effects by modulating mitochondria functions and they have significant implications in cancer therapy. Mitochondria- targeted therapy is a promising strategy in cancer treatment as these organelles play a crucial function in the regulation of apoptosis and metabolism in tumor cells and are more vulnerable to hyperthermia and oxidative damage. The aim of this review is used to explore the targeting efficacy of mitocans in the nanotherapeutic formulation when combined with therapies like PDT, PTT, RDT. We searched several databases include Pubmed, relemed, scopus, google scholar, Embase and collected the related information to the efficacy of mitocans in nanotherapeutics when combined with photo-radiotherapy to target chemo/radio-resisant tumor cells. In this review, we vividly described research reports pertinent to the selective delivery of chemotherapy molecules into specific sub-organelles which can significantly improve the efficiency of cancer treatment by targeting tumor cell metabolism. Furthermore, the rational design, functionalization and application of various mitochondrial targeting units, including organic phosphine/sulfur salts, quaternary ammonium salts, transition metal complexes, and mitochondria-targeted cancer therapy such as PDT, PTT, RDT, and others were summarized. Mainly, the efficacy of these modalities against mtDNA and additional nanotherapeutic strategies with photosensitizers, or radiotherapy to target mitochondrial metabolism in tumor cells with chemo/radio-resistance were delineated. This review can benefit nanotechnologists, oncologists, and radiation oncologists to develop rational designs and application of novel mitochondrial targeting drugs mainly to target metabolism in chemo/radio-resistant cancer cells in cancer therapy.

20.
Healthcare (Basel) ; 11(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37893833

RESUMO

In recent years, there has been the notable emergency of artificial intelligence (AI) as a transformative force in multiple domains, including orthodontics. This review aims to provide a comprehensive overview of the present state of AI applications in orthodontics, which can be categorized into the following domains: (1) diagnosis, including cephalometric analysis, dental analysis, facial analysis, skeletal-maturation-stage determination and upper-airway obstruction assessment; (2) treatment planning, including decision making for extractions and orthognathic surgery, and treatment outcome prediction; and (3) clinical practice, including practice guidance, remote care, and clinical documentation. We have witnessed a broadening of the application of AI in orthodontics, accompanied by advancements in its performance. Additionally, this review outlines the existing limitations within the field and offers future perspectives.

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