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1.
J Agric Food Chem ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720452

RESUMO

The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 µg/mL that was superior to that of the agricultural fungicide boscalid (2.2 µg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 µM that was superior to that of boscalid (7.9 µM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.

2.
Colloids Surf B Biointerfaces ; 237: 113866, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38520952

RESUMO

The inhibition of platelet adhesion to collagen in exposed vessels represents an innovative approach to the treatment of atherosclerosis and thrombosis. This study aimed to engineer peptide-based nanoparticles that prevent platelet binding to subendothelial collagen by engaging with collagen with high affinity. We examined the interactions between integrin α2/ glycoprotein VI/ von Willebrand factor A3 domain and collagen, as well as between the synthesized peptide nanoparticles and collagen, utilizing molecular dynamics simulations and empirical assays. Our findings indicated that the bond between von Willebrand factor and collagen was more robust. Specifically, the sequences SITTIDV, VDVMQRE, and YLTSEMH in von Willebrand factor were identified as essential for its attachment to collagen. Based on these sequences, three peptide nanoparticles were synthesized (BPa: Capric-GNNQQNYK-SITTIDV, BPb: Capric-GNNQQNYK-VDVMQRE, BPc: Capric-GNNQQNYK-YLTSEMH), each displaying significant affinity towards collagen. Of these, the BPa nanoparticles exhibited the most potent interaction with collagen, leading to a 75% reduction in platelet adhesion.


Assuntos
Adesividade Plaquetária , Fator de von Willebrand , Fator de von Willebrand/metabolismo , Colágeno/química , Peptídeos/farmacologia , Peptídeos/metabolismo , Plaquetas/metabolismo
3.
Cell Death Dis ; 15(3): 215, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485986

RESUMO

The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma de Células Escamosas , Exossomos , Neoplasias de Cabeça e Pescoço , MicroRNAs , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/patologia , MicroRNAs/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Exossomos/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Linhagem Celular Tumoral , Hipóxia/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Microambiente Tumoral/genética
5.
Cell Death Dis ; 14(8): 517, 2023 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-37573347

RESUMO

Ubiquitination is a reversible process that not only controls protein synthesis and degradation, but also is essential for protein transport, localization and biological activity. Deubiquitinating enzyme (DUB) dysfunction leads to various diseases, including cancer. In this study, we aimed to explore the functions and mechanisms of crucial DUBs in head and neck squamous cell carcinoma (HNSCC). Based on bioinformatic analysis and immunohistochemistry detection, YOD1 was identified to be significantly downregulated in HNSCC specimens compared with adjacent normal tissues. Further analysis revealed that reduced YOD1 expression was associated with the malignant progression of HNSCC and indicated poor prognosis. The results of the in vitro and in vivo experiments verified that YOD1 depletion significantly promoted growth, invasion, and epithelial-mesenchymal transition in HNSCC. Mechanistically, YOD1 inhibited the activation of the ERK/ß-catenin pathway by suppressing the ubiquitination and degradation of TRIM33, leading to the constriction of HNSCC progression. Overall, our findings reveal the molecular mechanism underlying the role of YOD1 in tumor progression and provide a novel potential therapeutic target for HNSCC treatment.


Assuntos
Neoplasias de Cabeça e Pescoço , Ubiquitina-Proteína Ligases , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Ubiquitinação , Enzimas Desubiquitinantes/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Transição Epitelial-Mesenquimal , Fatores de Transcrição/metabolismo , Endopeptidases/metabolismo , Tioléster Hidrolases/metabolismo
6.
Transl Behav Med ; 13(10): 794-803, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37318360

RESUMO

Provider physical activity referrals are recommended for cancer survivors, though barriers exist to clinical system integration. To develop and test ActivityChoice, an electronic referral (eReferral) clinic implementation program referring cancer survivors to physical activity programs of their choice. In Phase 1, we conducted semi-structured interviews with Cancer Center clinicians (n = 4) and cancer-focused physical activity program leaders (n = 3) assessing adaptations needed to implement an eReferral previously designed for another context. In Phase 2, we pilot-tested clinician-delivered referrals to survivors in two 12-week Plan, Do, Study, Act (PDSA) cycles. We examined feasibility using descriptive statistics (clinicians' adoption and engagement, patient referrals, and physical activity program enrollment) and acceptability through semi-structured interviews with enrolled clinicians (n = 4) and referred patients (n = 9). ActivityChoice included a secure referral webform, text message/email referral confirmations, clinician training/booster sessions, visual reminders, and referrals to in-person or virtual group physical activity programs. Results for each PDSA cycle respectively included: 41% (n = 7) and 53% (n = 8) of clinicians adopted ActivityChoice; 18 and 36 patients were referred; 39% (n = 7) and 33% (n = 12) of patients enrolled in programs, and 30% (n = 4) and 14% (n = 5) of patients deferred enrollment. Patients and clinicians appreciated the referrals and choices. A printed handout describing both programs was added to the clinic workflow for Cycle 2, which yielded more referrals, but lower program enrollment rates. Clinic-based eReferrals to choices of physical activity programs were feasible and acceptable by clinicians and patients. Added clinic workflow support may facilitate referrals.


Physical activity can improve the health, quality of life, and longevity among cancer survivors. Patients want to receive physical activity referrals and guidance from their cancer care team, but clinicians lack the knowledge, resources, time, and methods to counsel and refer their patients to community-based physical activity programs. One solution is to create a comprehensive electronic referral (eReferral) system giving cancer care clinicians the tools to support and refer their patients. We developed a simple eReferral that allows clinicians to refer patients to existing, evidence-based physical activity programs led by qualified exercise professions, LIVESTRONG at the YMCA (in-person) and Fit Cancer (virtual). We pilot tested the system with clinicians in two 12-week cycles. Clinicians were excited about the program and like the options they had to offer patients while providing suggestions on how we could better integrate it into their work environment. Patients appreciated the referral from their trusted cancer care clinician and appreciated choices of an in-person and virtual program to accommodate their preferences. To improve patient referrals and enrollment in physical activity programs, a more detailed printed handout that explains the benefits of physical activity in survivorship and describes each of the programs in detail may be helpful.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Exercício Físico , Encaminhamento e Consulta , Neoplasias/terapia
7.
Front Plant Sci ; 14: 1174697, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37384364

RESUMO

Plant litter is not only the major component of terrestrial ecosystem net productivity, the decomposition of which is also an important process for the returns of elements, including sodium (Na) and aluminum (Al), which can be beneficial or toxic for plant growth. However, to date, the global characteristics and driving factors of Na and Al concentrations in freshly fallen litter still remain elusive. Here, we evaluated the concentrations and drivers of litter Na and Al with 491 observations extracted from 116 publications across the globe. Results showed that (1) the average concentrations of Na in leaf, branch, root, stem, bark, and reproductive tissue (flowers and fruits) litter were 0.989, 0.891, 1.820, 0.500, 1.390, and 0.500 g/kg, respectively, and the concentrations of Al in leaf, branch, and root were 0.424, 0.200 and 1.540 g/kg, respectively. (2) mycorrhizal association significantly affected litter Na and Al concentration. The highest concentration of Na was found in litter from trees associated with both arbuscular mycorrhizal fungi (AM) and ectomycorrhizal fungi (ECM), followed by litter from trees with AM and ECM. Lifeform, taxonomic, and leaf form had significant impacts on the concentration of Na and Al in plant litter of different tissues. (3) leaf litter Na concentration was mainly driven by mycorrhizal association, leaf form and soil phosphorus concentration, while leaf litter Al concentration was mainly controlled by mycorrhizal association, leaf form, and precipitation in the wettest month. Overall, our study clearly assessed the global patterns and influencing factors of litter Na and Al concentrations, which may help us to better understand their roles in the associated biogeochemical cycles in forest ecosystem.

8.
Cell Signal ; 108: 110725, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37230199

RESUMO

BACKGROUND: Both microRNA-21-5p (miR-21) and the tumor microenvironment, including hypoxia and cancer-associated fibroblasts (CAFs), play a vital role in head and neck squamous cell carcinoma (HNSCC), but whether there is an interaction and the specific regulatory mechanism between them in the process of metastasis is still unclear. In this study, we aimed to elucidate the connection and regulatory mechanism of miR-21, hypoxia, and CAFs in HNSCC metastasis. METHODS: The underlying mechanisms of hypoxia inducible factor 1 subunit alpha (HIF1α) regulating miR-21 transcription, promoting exosome secretion, CAFs activation, tumor invasion, and lymph node metastasis were determined through quantitative real-time PCR, immunoblotting, transwell, wound healing, immunofluorescence, ChIP, electron microscopy, nanoparticle tracking analysis, dual-luciferase reporter assay, co-culture model and xenografts experiments. RESULTS: MiR-21 promoted the invasion and metastasis of HNSCC in vitro and in vivo, whereas HIF1α knockdown inhibited these processes. HIF1α upregulated transcription of miR-21 and promoted the release of exosomes from HNSCC cells. Exosomes derived from hypoxic tumor cells were rich in miR-21, which induced NFs activation towards CAFs by targeting YOD1. Knockdown the expression level of miR-21 in CAFs prevented lymph node metastasis in HNSCC. CONCLUSION: Hypoxic tumor cell-derived exosomal miR-21 might be a therapeutic target to prevent or delay HNSCC invasion and metastasis.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias de Cabeça e Pescoço , MicroRNAs , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Fibroblastos Associados a Câncer/metabolismo , MicroRNAs/metabolismo , Metástase Linfática/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral
9.
Mol Med Rep ; 27(5)2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37026508

RESUMO

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that a data panel portraying cell migration and invasion assay data shown in Fig. 7C was strikingly similar to a panel that had appeared in another article by different authors at a different research institute, which had been submitted for publication earlier than the submission date of this article. Moreover, a large number of overlapping data panels were identified comparing the data in Figs. 4A and B and 7C and D. Owing to the fact that the contentious data in Fig. 7C in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 14: 2127-2134, 2016; DOI: 10.3892/mmr.2016.5477].

10.
Cell Death Dis ; 14(2): 149, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36813772

RESUMO

Long non-coding RNAs (LncRNAs) are implicated in malignant progression of human cancers. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known lncRNA, has been reported to play crucial roles in multiple malignancies including head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of MALAT1 in HNSCC progression remain to be further investigated. Here, we elucidated that compared with normal squamous epithelium, MALAT1 was notably upregulated in HNSCC tissues, especially in which was poorly differentiated or with lymph nodes metastasis. Moreover, elevated MALAT1 predicted unfavorable prognosis of HNSCC patients. The results of in vitro and in vivo assays showed that targeting MALAT1 could significantly weaken the capacities of proliferation and metastasis in HNSCC. Mechanistically, MALAT1 inhibited von Hippel-Lindau tumor suppressor (VHL) by activating EZH2/STAT3/Akt axis, then promoted the stabilization and activation of ß-catenin and NF-κB which could play crucial roles in HNSCC growth and metastasis. In conclusion, our findings reveal a novel mechanism for malignant progression of HNSCC and suggest that MALAT1 might be a promising therapeutic target for HNSCC treatment.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste , Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína Supressora de Tumor Von Hippel-Lindau , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , NF-kappa B/genética , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética
11.
Eur J Med Res ; 28(1): 5, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597158

RESUMO

BACKGROUND: Cervical lymph node metastasis from unknown primary sites is a challenging clinical issue with a changing therapy model and unpredictable outcomes, which leads to the difficulty in selecting optimal treatments. Thus, it is valuable to analyze the clinical characteristics and outcomes of the patients who receive different management styles. METHODS: All patients with cervical lymph node metastasis from unknown primary sites were reviewed and no primary lesions were found. In addition, this work was funded by the Clinical Trial Fund Project of Tianjin Medical University Cancer Institute and Hospital (No. C1716). Specifically, we used univariate, multiple regression analysis to evaluate the factors associated with prognosis. RESULTS: 365 patients met the inclusion criteria, and the 2- and 5-year survival rates were 77.0% and 33.4%, respectively, with a median survival of 45 months. Gender, age, pathological type, nodal status, and necessary cervical lymph node dissection affected locoregional control. Distant metastasis was common in individuals with a pathological type of adenocarcinoma, poor differentiation, and advanced nodal status. Furthermore, patients who received induction chemotherapy had a better prognosis than those treated with postoperative chemotherapy. Multiple regression analysis showed that pathological grade, treatment models, and distant metastasis were associated with overall survival (OS) and progression-free survival (PFS). In addition, local recurrence exerted a significant influence on OS. Induction chemotherapy and postsurgical radiotherapy seemed to improve the prognosis of patients at the advanced stage compared with simple surgery and postsurgical chemotherapy. CONCLUSIONS: Pathological grade, treatment models, and distant metastasis were independent risk factors for prognosis. Induction chemotherapy or postoperative radiotherapy benefited patients at the advanced stage, and patients with adenocarcinoma, poor differentiation, and advanced nodal status should undergo induction chemotherapy in light of the increased risk of distant metastasis.


Assuntos
Adenocarcinoma , Neoplasias Primárias Desconhecidas , Neoplasias do Colo do Útero , Humanos , Feminino , Metástase Linfática/patologia , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/cirurgia , Estudos Retrospectivos , Linfonodos/patologia , Excisão de Linfonodo , Prognóstico , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Taxa de Sobrevida , Recidiva Local de Neoplasia
12.
Int J Biol Macromol ; 227: 193-202, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549027

RESUMO

As nanotechnology is applied clinical medicine, nanoparticle-based therapy is emerging as a novel approach for the treatment of atherosclerosis. Ligand-receptor interaction affects the effectiveness of nanoparticle targeting therapy. In this study, the biomimetic peptide (BP-KFFVLK-WYKDGD) ligand specifically targeting the lysophosphatidylcholine (LPC) receptor in atherosclerotic plaques was constructed. The corresponding ligand-receptor interaction under different pH values was investigated by molecular dynamics simulation and experimental measurements. Results show that the interaction force between the peptide and LPC is greater than that of the peptide and human umbilical vein endothelial cell, clearly demonstrating the specific targeting of the peptide ligand to the LPC receptor. The ligand-receptor binding of peptide and LPC dominantly depends on Coulomb and van der Waals interactions. The YKDG amino acids of the peptide are the main fragment that binds to LPC. Compared with neutral environment at pH 7.4, the interaction forces between the peptide and oxidized low-density lipoprotein (oxLDL) decreased by 18.22 % and 45.87 % under acidic environments at pH 6.5 and 5.5, respectively, because of the change in oxLDL secondary structure and the release of LPC from oxLDL. Nevertheless, the peptide still has a strong binding capacity with oxLDL for the treatment of atherosclerosis.


Assuntos
Aterosclerose , Lisofosfatidilcolinas , Humanos , Lisofosfatidilcolinas/metabolismo , Ligantes , Biomimética , Lipoproteínas LDL/metabolismo , Peptídeos/farmacologia
13.
Sci Total Environ ; 857(Pt 3): 159686, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36302428

RESUMO

Plant litter decomposition is not only the major source of soil carbon and macronutrients, but also an important process for the biogeochemical cycling of trace elements such as iron (Fe), manganese (Mn), zinc (Zn), and copper (Cu). The concentrations of plant litter trace elements can influence litter decomposition and element cycling across the plant and soil systems. Yet, a global perspective of the patterns and driving factors of trace elements in plant litter is missing. To bridge this knowledge gap, we quantitatively assessed the concentrations of four common trace elements, namely Fe, Mn, Zn, and Cu, of freshly fallen plant litter with 1411 observations extracted from 175 publications across the globe. Results showed that (1) the median of the average concentrations of litter Fe, Mn, Zn, and Cu were 0.200, 0.555, 0.032, and 0.006 g/kg, respectively, across litter types; (2) litter concentrations of Fe, Zn, and Cu were generally stable regardless of variations in multiple biotic and abiotic factors (e.g., plant taxonomy, climate, and soil properties); and (3) litter Mn concentration was more sensitive to environmental conditions and influenced by multiple factors, but mycorrhizal association and soil pH and nitrogen concentration were the most important ones. Overall, our study provides a clear global picture of plant litter Fe, Mn, Zn, and Cu concentrations and their driving factors, which is important for improving our understanding on their biogeochemical cycling along with litter decomposition processes.


Assuntos
Manganês , Oligoelementos , Manganês/análise , Zinco/análise , Cobre/análise , Oligoelementos/análise , Solo/química , Ferro/análise , Plantas , Íons
14.
Front Oncol ; 12: 909723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36203449

RESUMO

Objective: We analysed the diagnostic performance of thyroglobulin in fine-needle aspiration (FNA-Tg) in the suspicious lateral cervical lymph nodes (CLNs) in patients with papillary thyroid cancer (PTC), proposed the best cutoff value and discussed the factors that may affect the diagnostic value of FNA-Tg. Methods: In the present study, a retrospective analysis of 403 patients with PTC with 448 suspected lateral CLNs metastasis from October 2019 to May 2021 was performed. The cutoff value according to the receiver operating characteristic (ROC) curve was determined, and the Wilcoxon rank-sum test was used to evaluate the correlation between FNA-Tg and factors. Results: According to the ROC curve, the cutoff value of FNA-Tg was 3.69 ng/ml (sensitivity, 92.48%; specificity, 75.00%). Patients who underwent total thyroidectomy were excluded. Compared with US and FNAC, the diagnostic performance of FNA-Tg was the greatest, especially for small CLNs (diameter ≤ 1 cm), cystic CLNs, and patients with Hashimoto's thyroiditis (HT). Moreover, FNA-Tg levels were correlated with the presence of HT (p = 0.003), the anti-thyroglobulin antibody (Tg-Ab) (p < 0.001), the ratio of metastatic lateral CLNs (p = 0.004) and Tg assay kits (p < 0.001). Conclusions: FNA-Tg measurement is sensitive enough for diagnosing lateral CLN metastases from PTC, but its diagnostic value is compromised by a number of factors.

15.
Colloids Surf B Biointerfaces ; 219: 112836, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36115264

RESUMO

Polypeptide nano-carriers with deformation and sustained-release function have gained an attention in anti-tumor treatment. A multifunctional polypeptide with different motifs was discussed and the contribution of each motif to targeted drug release was analyzed by control studies. The transformation and drug release processes of polypeptides were investigated by molecular dynamics method to reveal their dynamics mechanism, and corresponding experiments were performed to verify the simulation results. We observed that the polypeptides could form NPs under the hydrophobic interaction between self-assembly motifs and the electrostatic repulsion between targeting motifs. Affected by the ligand-receptor interaction, the targeting motifs overcame the electrostatic repulsion to approach the ligand proteins, leading to the promotion of the binding of fibrous motifs and the transformation of NPs into NFs for better retention of drugs in the tumor tissues. In addition, the polypeptides with strong hydrophobicity exhibited excellent sustained-release efficiency. These insights allow drawing general conclusions contributed to the design of transformable polypeptide NPs: The decrease in the hydrophobicity of self-assembly motifs is beneficial for the enrichment of doxorubicin in tumor tissues, as well as the similar result can be obtained with the improvement of the hydrophobicity of fibrous motifs and the capability of target.

16.
Gland Surg ; 11(6): 1047-1056, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35800750

RESUMO

Background: The optimal extent of lymph node (LN) dissection in the management of N1b papillary thyroid microcarcinoma (PTMC) is still under debate in clinical practice, so we aimed to identify the risk factors associated with multilevel lateral lymph node metastasis (LLNM) with regard to the extent of LN dissection. Methods: The clinical data of 182 N1b PTMC patients between January 2019 and June 2021 at Tianjin Medical University Cancer Institute and Hospital were retrospectively reviewed. The frequency pattern and distribution of LLNM were analyzed for risk factors. We assessed the diagnostic value of preoperative ultrasonography (USG) for identifying levels II-V metastasis in PTMC patients. Results: The proportion of multilevel LLNM in N1b PTMC was 72.1%, and the most common pattern was metastasis at two levels (41.2%). Capsule invasion [odds ratio (OR) =6.861, 95% confidence interval (CI): 1.462-32.190, P=0.015], upper pole [OR =2.125, 95% CI: 1.010-4.473, P=0.047], central LN ratio [OR =7.315, 95% CI: 1.309-40.877, P=0.023], thyroid-stimulating hormone (TSH) >1.5 mIU/mL [OR =2.773, 95% CI: 1.269-6.060, P=0.011], and extranodal extension (ENE) [OR =2.632, 95% CI: 1.207-5.739, P=0.015] were independent risk factors for multilevel metastasis. In addition, unltrasonography had high sensitivity and specificity in the diagnosis of metastasis at level V (75.0%, 78.4%) and multilevel LLNM (67.2%, 64.8%). Conclusions: Modified radical neck dissection (MRND) in N1b PTMC patients may be reserved for patients with simultaneous 3-level LLNM or clinically evident metastasis at level V. Preoperative USG may have certain suggestive significance in the diagnosis of multilevel LLNM in primary PTMC.

17.
Int J Biol Macromol ; 209(Pt A): 785-793, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429517

RESUMO

Drug-loaded pH-responsive nanoparticles are potential drug carriers in nanotherapeutics delivery because they can remain stable in normal tissues but can disassemble and release drug molecules in tumors. In this study, the mechanisms of self-assembly and disassembly were investigated by analyzing the characteristics of three kinds of biomimetic peptides with different components and sequences. The structural parameters and energy changes during self-assembly and disassembly were calculated by molecular dynamics simulation. Transmission electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy were used to observe morphological changes and measure the strength of hydrophobic and hydrophilic interactions between peptides. Results show that the hydrophobic and hydrophilic interactions play crucial roles in the self-assembly and disassembly processes of peptides. The structure of the peptide clusters after self-assembly became tighter as the difference between hydrophobic and hydrophilic interactions increased, whereas a decrease in this difference led to the increased disassembly of the peptides. In general, polyethylene glycol chain modification was necessary in disassembly, and peptides with straight structures had stronger disassembly ability than that with branched structures with the same components. The morphology of peptide clusters can be controlled under different pH values by changing the composition and structure of the peptides for enhanced drug retention and sustained release.


Assuntos
Biomimética , Simulação de Dinâmica Molecular , Portadores de Fármacos/química , Interações Hidrofóbicas e Hidrofílicas , Peptídeos/química
18.
Nanoscale ; 14(10): 3899-3906, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35212699

RESUMO

A binding-induced fibrillogenesis (BIF) peptide mimics the fibrillogenesis of fibronectin, forming fibrous networks for disease theranostics. However, the mechanism of fast fibrillogenesis of the BIF peptide remains unclear. In this study, the fibrillogenesis processes of the BIF peptide in the absence and presence of receptors, i.e. Ca2+, are carefully studied. The BIF peptide, lauric acid-FFVLK-HSDVHK (LAFH) can self-assemble into nanoparticles (NPs) in solution and further transform into a fibrous structure, the fibrillogenesis of which could be accelerated by the addition of Ca2+. In detail, the fibrillogenesis of LAFH NPs without Ca2+ is achieved through a nucleation-elongation mechanism, in which homogeneous secondary nucleation is involved, followed by detachment of the newly formed fibers from pre-formed nanofibers (NFs). The fibrillogenesis of LAFH NPs in the presence of Ca2+ starts with an Ostwald ripening process, followed by a heterogeneous secondary nucleation, in which LAFH NPs bind to pre-formed LAFH NFs via Ca2+. The phenomenon of heterogeneous secondary nucleation including the attachment and shape change of LAFH NPs on pre-formed LAFH NFs is first revealed by TEM observation. These findings contribute to the understanding of the fast BIF process, supporting the mechanism study at the cellular level.


Assuntos
Nanofibras , Nanopartículas , Peptídeos/química
19.
Hand (N Y) ; 17(2): 346-353, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-32506966

RESUMO

Background: Benign tumors of the hand present in a wide array of histological subtypes and compose most of the bony tissue tumors in the hand. This study evaluates the characteristics and treatment of benign bone tumors in light of one institution's experience. Methods: Histologically confirmed benign tumors of the hand were retrospectively identified using International Classification of Diseases codes from 1992 to 2015. A medical chart review was conducted to collect patient characteristics and tumor epidemiology and treatment. Results: A total of 155 benign bone tumors were identified. The median age of patients at the time of surgery was 39.9 ± 12.8 years. All bone tumors were located in the digits, and most were treated by intralesional curettage (n = 118, 76%). Pathologic fractures occurred in 79 bone tumors (51%). Conclusion: Enchondromas (n = 118, 76%) were the most common bone tumor in this series, whereas giant cell tumors were the most destructive and also had the highest recurrence rate (40%). Awareness of tumor features may help physicians with diagnosis, and awareness of recurrence rates is important when counseling patients.


Assuntos
Neoplasias Ósseas , Condroma , Adulto , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Condroma/patologia , Condroma/cirurgia , Curetagem , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
Hand (N Y) ; 17(3): 519-528, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-32666834

RESUMO

Background: Benign soft-tissue tumors of the hand are more common than both their benign bone and malignant soft-tissue counterparts. This study evaluates the characteristics and treatment of benign soft tissue tumors in light of 1 institution's experience. Methods: Histologically confirmed benign soft-tissue tumors of the hand were retrospectively identified using International Classification of Disease codes from 1992 to 2015. A medical chart review was conducted to collect patient demographics, tumor epidemiology, and treatment. Results: A total of 199 soft-tissue tumors were identified. The median patient age at time of treatment was 47.4 ± 14.7 years in age. The majority of tumors were located in the digits (n = 168, 84%) and treated by excision (n = 191, 96%). Localized type tenosynovial giant cell tumors (n = 71, 36%) were the most common and had the highest rates of recurrence (8.5%) in this series. Other frequent histologies included hemangioma, schwannoma, and glomus tumors. Conclusion: Awareness and understanding of tumor characteristics may help physicians with diagnosis and treatment. There is an extensive variety of tumors, but the principles of clinical and imaging diagnosis are common to all of them. Marginal excision for the treatment pain, improvement of function, and cosmetic correction applies to all these tumors independent of the histology.


Assuntos
Tumor de Células Gigantes de Bainha Tendinosa , Neoplasias de Tecidos Moles , Tumor de Células Gigantes de Bainha Tendinosa/diagnóstico , Tumor de Células Gigantes de Bainha Tendinosa/epidemiologia , Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Mãos/patologia , Mãos/cirurgia , Humanos , Estudos Retrospectivos , Neoplasias de Tecidos Moles/epidemiologia , Neoplasias de Tecidos Moles/cirurgia
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