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1.
J Org Chem ; 89(1): 356-362, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38096380

RESUMO

A novel class of multiple B←N Lewis pair-functionalized polycyclic aromatic hydrocarbons with different BR2 groups (R = Cl or Et) directly attached at positions 1, 6, and 11 of triazatruxene was synthesized. The triazatruxene backbone of 4 displays a bowl shape, and its molecular skeleton shows a highly twisted propeller-like structure with C3 symmetry. The introduction of B←N Lewis pairs not only results in a large decrease in the HOMO-LUMO gap but also lowers the LUMO to -3.00 eV. Both compounds show excellent stability with large Stokes shifts of ≤8234 cm-1 and solvatochromic emission in solvents of different polarities.

2.
Rapid Commun Mass Spectrom ; 38(16): e9849, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38887896

RESUMO

RATIONALE: This study used proteomics-based data-independent acquisition (DIA) technology with the aim of screening for differential expression proteins in type I gastric neuroendocrine neoplasm (g-NEN). METHODS: Differential expression proteins in type I g-NEN and peritumoral tissues were screened using DIA with liquid chromatography/tandem mass spectrometry (DIA-LC/MS/MS). The identified proteins were then functionally analysed using bioinformatics methods. We selected the three most highly expressed proteins, combined with patients' clinical data, for prognostic analysis. RESULTS: Compared with peritumoral tissues, 224 proteins were up-regulated, and 70 were down-regulated. The most significantly enriched biological processes and pathways were vacuolar proton-transporting V-type ATPase complex assembly and metabolism-related pathways. PCSK1, FBXO2, ACSL1, IRS2, and PTPRZ1 expression was markedly up-regulated in type I g-NENs. High IRS2 expression significantly correlated with a shorter time to recurrence. CONCLUSIONS: Our study provides a comprehensive proteomic signature based on DIA-LC/MS/MS and highlights high IRS2 expression as a potential prognostic marker for type I gNENs.


Assuntos
Biomarcadores Tumorais , Tumores Neuroendócrinos , Proteômica , Neoplasias Gástricas , Espectrometria de Massas em Tandem , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/química , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Espectrometria de Massas em Tandem/métodos , Masculino , Feminino , Cromatografia Líquida/métodos , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/química , Prognóstico , Proteômica/métodos , Pessoa de Meia-Idade , Adulto , Idoso , Proteoma/análise , Proteoma/metabolismo , Espectrometria de Massa com Cromatografia Líquida
3.
Org Biomol Chem ; 22(8): 1676-1685, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38299623

RESUMO

We report herein a way to prepare and purify optoelectronic functional 4,9- and 4,10-substituted pyrene isomers. By tuning the size of substituents, the designed 4,9- and 4,10-isomers can be successfully isolated by recycling preparative size-exclusion chromatography (SEC) and/or repeated recrystallization. The structure and purity of the isolated compounds 1-5 have been confirmed by 1H NMR, 13C NMR, and HRMS. The photophysical and electrochemical properties of compounds 1-5 have been studied in detail both experimentally and theoretically. The lowest transitions of these pyrenes, 1-5, are allowed, with moderate to high fluorescence quantum yields and radiative decay rates around 108 s-1. The differences between the electrochemical and photophysical properties of 4,9-, 4,10-, 1,6-, and 2,7-substituted isomers are compared and concluded.

4.
Anal Chem ; 95(41): 15350-15356, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37784219

RESUMO

Lipid droplets (LDs) are crucial organelles used to store lipids and participate in lipid metabolism in cells. The abnormal aggregation and polarity change of LDs are associated with the occurrence of diseases, such as steatosis. Herein, the polarity-sensitive probe TBPCPP with a donor-acceptor-π-acceptor (D-A-π-A) structure was designed and synthesized. The TBPCPP has a large Stokes shift (∼220 nm), excellent photostability, high LD targeting, and considerable two-photon absorption (TPA) cross-section (∼226 GM), enabling deep two-photon imaging (∼360 µm). In addition, the fluorescence lifetime of TBPCPP decreases linearly with increasing solvent polarity. Therefore, with the assistance of two-photon fluorescence lifetime imaging microscopy (TP-FLIM), TBPCPP has successfully achieved not only the visualization of polarity changes caused by LD accumulation in HepG-2 cells but also lipid-specific imaging and visualization of different polarities in lipid-rich regions in zebrafish for the first time. Furthermore, TP-FLIM revealed that the polarity gradually decreases during steatosis in HepG-2 cells, which provided new insights into the diagnosis of steatosis.


Assuntos
Gotículas Lipídicas , Peixe-Zebra , Animais , Gotículas Lipídicas/química , Microscopia de Fluorescência/métodos , Fótons , Lipídeos/análise , Corantes Fluorescentes/química
5.
BMC Surg ; 23(1): 147, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37264328

RESUMO

BACKGROUND: There are only a few epidemiological reports available for reference. The clinicopathological features are not clear, so there is no consensus on treating rectal multiple neuroendocrine neoplasms. This study aims to summarize the clinicopathological characteristics and preliminarily discuss the clinical diagnosis and treatment of rectal multiple neuroendocrine neoplasms. METHODS: This study retrospectively analyzed rectal neuroendocrine neoplasm patients diagnosed and treated at the Fourth Hospital of Hebei Medical University from February 2007 to May 2021. The clinicopathological characteristics of rectal multiple neuroendocrine neoplasms were summarized and analyzed in combination with 14 studies on rectal multiple neuroendocrine neoplasms. RESULTS: The incidence of RM-NENs accounted for 3.8% of all R-NENs in this study. The number of tumors varied to some extent, the size of tumors was basically no more than 10 mm, and there were more G1 grade tumors. In the analysis of 46 cases with known lymph node metastasis, the difference in lymph node metastasis rate between the number of tumors < 8 and ≥ 8 was statistically significant (p = 0.002). CONCLUSIONS: The incidence of rectal multiple neuroendocrine neoplasms accounted for 3.8% of all rectal neuroendocrine neoplasms. For rectal multiple neuroendocrine neoplasms, the lymph node metastasis rate was higher when the number of tumors was ≥ 8. The influence of the number of tumors on lymph node metastasis should be considered in the selection of treatment.


Assuntos
Tumores Neuroendócrinos , Neoplasias Retais , Humanos , Prognóstico , Metástase Linfática , Estudos Retrospectivos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Neoplasias Retais/diagnóstico , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia
6.
Molecules ; 28(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37764402

RESUMO

As a class of highly dynamic organelles, lipid droplets (LDs) are involved in numerous physiological functions, and the changes in polarity of LDs are closely related to a variety of diseases. In this work, we developed two polarity-sensitive fluorescent probes (CC-CH and CC-Cl) based on curcumin analogs. CC-CH and CC-Cl with a donor-acceptor-donor (D-A-D) structure exhibited the property of intramolecular charge transfer (ICT); thus, their fluorescence emissions were significantly attenuated with increasing ambient polarity. Cell experiments indicated that CC-CH and CC-Cl showed excellent photostability, a low cytotoxicity, and a superior targeting ability regarding LDs. After treatment with oleic acid (OA) and methyl-ß-cyclodextrin (M-ß-CD), the polarity changes of LDs in living cells could be visualized by using CC-CH and CC-Cl. In addition, CC-CH and CC-Cl could monitor polarity changes of LDs in different pathological processes, including inflammatory responses, nutrient deprivation, and H2O2-induced oxidative stress. Therefore, CC-CH and CC-Cl are promising potential fluorescent probes for tracking intracellular LD polarity changes.

7.
Rapid Commun Mass Spectrom ; 36(18): e9355, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-35840340

RESUMO

BACKGROUND: Gastroesophageal junction adenocarcinoma (GEJA) is a malignant tumor located at the junction of the esophagus and stomach, the incidence of which is increasing year by year, while screening for early biomarkers is limited. Tandem mass tagging (TMT) coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) has been used to screen for differential proteins in various cancers. METHODS: Differential proteins in GEJA and precancerous lesions were screened using TMT-LC/MS/MS, and then proteins that met expectations were selected for trend clustering analysis, combined with GO and KEGG analysis for functional annotation of differential proteins in GEJA. Then, parallel reaction monitoring and immunohistochemistry techniques were used to validate the accuracy of the proteomics data. RESULTS: Our group screened the differential proteins during GEJA progression using proteomics technology, analyzed the expression trends and functional regions involved in the differential proteins during carcinogenesis, and validated the accuracy of the experimental results. CONCLUSIONS: The screening of differential proteins in GEJA carcinogenesis based on TMT-LC/MS/MS technology provides detailed information for the elucidation of GEJA progression process, pathogenesis, early screening and screening of candidate markers.


Assuntos
Adenocarcinoma , Espectrometria de Massas em Tandem , Adenocarcinoma/diagnóstico , Biomarcadores/metabolismo , Carcinogênese , Cromatografia Líquida/métodos , Neoplasias Esofágicas , Junção Esofagogástrica/metabolismo , Humanos , Espectrometria de Massas em Tandem/métodos
8.
Int J Colorectal Dis ; 37(2): 421-428, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34997303

RESUMO

PURPOSE: The detection rate of colorectal neuroendocrine tumours (CR-NETs) is increasing, but their treatment is still controversial. Lymph node metastasis is an important reference index for the selection of treatment. The aim of our study was to investigate the factors associated with lymph node metastasis and prognosis of CR-NETs. METHODS: The case characteristics of patients with colorectal neuroendocrine tumours from January 2011 to December 2020 were retrospectively analysed, including age, gender, tumour size, tumour location, lymph node metastasis, pathological grade and follow-up. RESULTS: A total of 195 cases of CR-NETs were included in this study. When 15 mm was used as the cut-off value, the sensitivity, specificity and area under the curve (AUC) of lymph node metastases were 95.9%, 95.2% and 0.986, respectively. Multivariate analysis suggested that tumour size ≥ 15 mm (OR: 30.517, 95% CI: 1.250 ~ 744.996, p = 0.036) and lymphovascular invasion (OR: 42.796, 95% CI: 2.882 ~ 635.571, p = 0.006) were independent risk factors for lymph node metastasis. Age ≥ 56 (HR: 7.434, 95% CI: 1.334 ~ 41.443, p = 0.022) and distant metastasis (HR: 24.487, 95% CI: 5.357 ~ 111.940, p < 0.001) were independent prognostic factors in multivariable analyses. CONCLUSIONS: When the size of a CR-NET is ≥ 15 mm, the risk of lymph node metastasis is higher, and it is recommended to choose the surgical method carefully. Tumour size and lymphovascular invasion were independent risk factors for lymph node metastasis. Age ≥ 56 and distant metastasis were independent prognostic factors.


Assuntos
Neoplasias Colorretais , Tumores Neuroendócrinos , Neoplasias Colorretais/patologia , Humanos , Linfonodos/patologia , Metástase Linfática , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco
9.
BMC Surg ; 22(1): 248, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761304

RESUMO

BACKGROUND: The aim of this study is to evaluate and compare the safety and efficacy of endoscopic mucosal resection with a cap (EMR-c) with those of endoscopic submucosal dissection (ESD) for rectal neuroendocrine tumors (R-NETs) ≤ 15 mm in diameter, and to analyze the risk factors of incomplete resection. METHODS: A total of 122 patients who underwent EMR-c or ESD for R-NETs at the Fourth Hospital of Hebei Medical University between February 2007 and December 2020 were invovled in this study. The clinical outcomes of two groups were compared and evaluated. RESULTS: A total of 122 patients with 128 R-NETs underwent endoscopic resection (EMR-c, 80; ESD, 48). In terms of duration of operation, EMR-c was significantly shorter than ESD (p < 0.001). Univariate analysis and multivariate analysis suggested that tumor diameter ≥ 8 mm was an independent risk factor for incomplete resection in patients with R-NETs in this study. CONCLUSIONS: Both EMR-c and ESD were safe and effective treatments for R-NETs ≤ 15 mm in diameter. In addition, tumor diameter ≥ 8 mm was an independent risk factor for incomplete resection.


Assuntos
Ressecção Endoscópica de Mucosa , Tumores Neuroendócrinos , Neoplasias Retais , Humanos , Mucosa Intestinal/patologia , Mucosa Intestinal/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
10.
Angew Chem Int Ed Engl ; 61(21): e202202005, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35257452

RESUMO

Facile tailoring of photosensitizers (PSs) with advanced and synergetic properties is highly expected to broaden and deepen photodynamic therapy (PDT) applications. Herein, a catalyst-free thiol-yne click reaction was employed to develop the sulfur atom-based PSs by using the in situ formed sulfur "heavy atom effect" to enhance the intersystem crossing (ISC), while such an effect can be remarkably magnified by the polymerization. The introduction of a tetraphenylpyrazine-based aggregation-induced emission (AIE) unit was also advantageous in PS design by suppressing their non-radiative decay to facilitate the ISC in the aggregated state. Besides, the resulting sulfur atom electron donor, together with a double-bond π bridge and AIE electron acceptor, created a donor-π-acceptor (D-π-A) molecular system with good two-photon excitation properties. Combined with the high singlet oxygen generation efficiency, the fabricated polymer nanoparticles exhibited an excellent in vitro two-photon-excited PDT towards cancer cells, therefore possessing a huge potential for the deep-tissue disease therapy.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Polimerização , Oxigênio Singlete , Enxofre
11.
J Am Chem Soc ; 141(38): 15111-15120, 2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31436971

RESUMO

Acrylonitriles with aggregation-induced emission (AIE) characteristics have been found to show promising applications in two-photon biomedical imaging. Generally, elaborate synthetic efforts are required to achieve different acrylonitriles with distinct functionalities. In this work, we first reported the synthesis of two different group-functionalized AIE-active acrylonitriles (TPAT-AN-XF and 2TPAT-AN) obtained simply by mixing the same reactants at different temperatures using a facile and transition metal-free synthetic method. These two AIE luminogens (AIEgens) exhibit unique properties such as bright red emission in the solid state, large Stokes shift, and large two-photon absorption cross section. Water-soluble nanoparticles (NPs) of 2TPAT-AN were prepared by a nanoprecipitation method. In vitro imaging data show that 2TPAT-AN NPs can selectively stain lysosome in live cells. Besides one-photon imaging, remarkable two-photon imaging of live tumor tissues can be achieved with high resolution and deep tissue penetration. 2TPAT-AN NPs show high biocompatibility and are successfully utilized in in vivo long-term imaging of mouse tumors with a high signal-to-noise ratio. Thus, the present work is anticipated to shed light on the preparation of a library of AIE-active functionalized acrylonitriles with intriguing properties for biomedical applications.


Assuntos
Acrilonitrila/química , Corantes Fluorescentes/química , Imagem Óptica , Fótons , Acrilonitrila/síntese química , Corantes Fluorescentes/síntese química , Estrutura Molecular
12.
Reprod Biol Endocrinol ; 17(1): 50, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262321

RESUMO

BACKGROUND: The placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET). METHODS: This study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated with IVF-ET procedures. Four human placental villi from first-trimester samples were obtained through fetal bud aspiration from patients subjected to IVF-ET due to oviductal factors. An additional four control human placental villi were derived from a group of subjects who spontaneously conceived a twin pregnancy. We analyzed their transcriptomes by microarray. Then, RT-qPCR and immunohistochemistry were utilized to analyze several dysregulated genes to validate the microarray results. Biological functions and pathways were analyzed with bioinformatics tools. RESULTS: A total of 3405 differentially regulated genes were identified as significantly dysregulated (> 2-fold change; P < 0.05) in the IVF-ET placenta in the first trimester: 1910 upregulated and 1495 downregulated genes. Functional enrichment analysis of the differentially regulated genes demonstrated that the genes were involved in more than 50 biological processes and pathways that have been shown to play important roles in the first trimester in vivo. These pathways can be clustered into coagulation cascades, immune response, transmembrane signaling, metabolism, cell cycle, stress control, invasion and vascularization. Nearly the same number of up- and downregulated genes participate in the same biological processes related to placental development and maintenance. Procedures utilized in IVF-ET altered the expression of first-trimester placental genes that are critical to these biological processes and triggered a compensatory mechanism during early implantation in vivo. CONCLUSION: These data provide a potential basis for further analysis of the higher frequency of adverse perinatal outcomes following IVF-ET, with the ultimate goal of developing safer IVF-ET protocols.


Assuntos
Transferência Embrionária , Fertilização in vitro , Placenta/metabolismo , Primeiro Trimestre da Gravidez/genética , Transcriptoma , Adulto , Vilosidades Coriônicas/metabolismo , Desenvolvimento Embrionário/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Gravidez , Resultado da Gravidez , Transdução de Sinais/genética
13.
Beilstein J Org Chem ; 14: 2074-2081, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30202460

RESUMO

A novel functional [2]rotaxane containing two alkenyl bonds was designed, synthesized and characterized by 1H, 13C NMR spectroscopy and HRESI mass spectrometry. The introduction of alkenyl bonds endowed the [2]rotaxane a fascinating ability to react with versatile functional groups such as alkenyl and thiol functional groups. The reversible shuttling movement of the macrocycle between two different recognition sites on the molecular thread can be driven by external acid and base. This kind of rotaxane bearing functional groups provides a powerful platform for preparing stimuli-responsive polymers.

14.
Adv Mater ; 36(3): e2308977, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37968865

RESUMO

Lung cancer is the second most prevalent cancer and the leading cause of cancer-related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments. Novel therapeutics have been exploited to address complicated resistance mechanisms of lung cancer and the advancement of nanomedicine is extremely promising in terms of overcoming drug resistance. Nanomedicine equipped with multifunctional and tunable physiochemical properties in alignment with tumor genetic profiles can achieve precise, safe, and effective treatment while minimizing or eradicating drug resistance in cancer. Here, this work reviews the discovered resistance mechanisms for lung cancer chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy, and outlines novel strategies for the development of nanomedicine against drug resistance. This work focuses on engineering design, customized delivery, current challenges, and clinical translation of nanomedicine in the application of resistant lung cancer.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Neoplasias , Humanos , Nanomedicina , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos
15.
Adv Sci (Weinh) ; 11(2): e2306230, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37953442

RESUMO

Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B-responsive polymeric nanoparticle prodrug system is employed for co-delivery of PTX and CAP, resulting in a polymeric nano-drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co-delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.


Assuntos
Paclitaxel , Neoplasias Gástricas , Humanos , Inibidores da Angiogênese , Catepsina B , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases , Polímeros , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Neoplasias Gástricas/tratamento farmacológico
16.
Adv Mater ; 36(18): e2311500, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38299748

RESUMO

The application of nanomedicines for glioblastoma (GBM) therapy is hampered by the blood-brain barrier (BBB) and the dense glioblastoma tissue. To achieve efficient BBB crossing and deep GBM penetration, this work demonstrates a strategy of active transcellular transport of a mitochondrion-disturbing nanomedicine, pGBEMA22-b-pSSPPT9 (GBEPPT), in the GBM tissue through mitocytosis. GBEPPT is computer-aided designed and prepared by self-assembling a conjugate of an amphiphilic block polymer and a drug podophyllotoxin (PPT). When GBEPPT is delivered to the tumor site, overexpressed γ-glutamyl transpeptidase (GGT) on the brain-blood endothelial cell, or the GBM cell triggered enzymatic hydrolysis of γ-glutamylamide on GBEPPT to reverse its negative charge to positive. Positively charged GBEPPT rapidly enter into the cell and target the mitochondria. These GBEPPT disturb the homeostasis of mitochondria, inducing mitocytosis-mediated extracellular transport of GBEPPT to the neighboring cells via mitosomes. This intracellular-to-intercellular delivery cycle allows GBEPPT to penetrate deeply into the GBM parenchyma, and exert sustainable action of PPT released from GBEPPT on the tumor cells along its penetration path at the tumor site, thus improving the anti-GBM effect. The process of mitocytosis mediated by the mitochondrion-disturbing nanomedicine may offer great potential in enhancing drug penetration through malignant tissues, especially poorly permeable solid tumors.


Assuntos
Glioblastoma , Mitocôndrias , Polímeros , Mitocôndrias/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Linhagem Celular Tumoral , Polímeros/química , Animais , Barreira Hematoencefálica/metabolismo , Podofilotoxina/química , Podofilotoxina/farmacologia , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Antineoplásicos/química , Antineoplásicos/farmacologia , gama-Glutamiltransferase/metabolismo , Portadores de Fármacos/química
17.
Adv Mater ; 36(15): e2312528, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240412

RESUMO

Genetic manipulations and pharmaceutical interventions to disturb lipid metabolism homeostasis have emerged as an attractive approach for the management of cancer. However, the research on the utilization of bioactive materials to modulate lipid metabolism homeostasis remains constrained. In this study, heptakis (2,3,6-tri-O-methyl)-ß-cyclodextrin (TMCD) is utilized to fabricate homomultivalent polymeric nanotraps, and surprisingly, its unprecedented ability to perturb lipid metabolism homeostasis and induce pyroptosis in tumor cells is found. Through modulation of the density of TMCD arrayed on the polymers, one top-performing nanotrap, PTMCD4, exhibits the most powerful cholesterol-trapping and depletion capacity, thus achieving prominent cytotoxicity toward different types of tumor cells and encouraging antitumor effects in vivo. The interactions between PTMCD4 and biomembranes of tumor cells effectively enable the reduction of cellular phosphatidylcholine and cholesterol levels, thus provoking damage to the biomembrane integrity and perturbation of lipid metabolism homeostasis. Additionally, the interplays between PTMCD4 and lysosomes also induce lysosomal stress, activate the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasomes, and subsequently trigger tumor cell pyroptosis. To sum up, this study first introduces dendronized bioactive polymers to manipulate lipid metabolism and has shed light on another innovative insight for cancer therapy.


Assuntos
Amidas , Ciclopropanos , Neoplasias , Piroptose , Humanos , Metabolismo dos Lipídeos , Homeostase , Colesterol , Neoplasias/tratamento farmacológico , Polímeros/metabolismo
18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(12): 1668-71, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24517067

RESUMO

OBJECTIVE: To observe changes of cholecystokinin octapeptide (CCK-8), calcitonin gene related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP) in each tissue of the digestive system of allergic asthma (AA) model rats. METHODS: The pulmonary disease (AA) rat model was duplicated by 1% ovalbumin. Its effect on the pathological morphology of the six main parts of the digestive system (stomach, duodenum, jejunum, ileum, colon and rectum) and related regulating factors such as CCK8, CGRP, SP, and VIP were observed. RESULTS: The pathological morphology of the lung was synchronously changed as that of the colon of model rats. But there was no obvious change in the stomach, duodenum, jejunum, ileum, or rectum. Significant changes occurred in CCK8 (79 961.4 +/- 12 577.9, 48 519.5 +/- 12 240.7), CGRP (41 950.1 +/- 12 600.1, 38 059.8 +/- 11 942.4), and SP (88 243.9 +/- 32 177.2, 47 417.8 +/- 16 462.4), and VIP (20 711.4 +/- 7 334.6, 43 208.1 +/- 13 433.8) of the lung tissue and the colon tissue of model rats (P < 0. 05, P < 0.01). But there was no significant change in the aforesaid substances of the stomach, duodenum, jejunum, ileum and rectum (P > 0.05). CONCLUSIONS: Pulmonary disease might affect the colon, inducing pathological changes of the colon tissue and changes of related regulating factors such as CCK8, CGRP, SP, and VIP. It showed no significant effect on the stomach, duodenum, jejunum, ileum and rectum.


Assuntos
Asma/metabolismo , Colo/metabolismo , Pulmão/metabolismo , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Sincalida/metabolismo , Substância P/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo
19.
BMC Prim Care ; 24(1): 257, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037007

RESUMO

BACKGROUND: By investigating the knowledge, medication, occurrence of complications, and risks among elderly non-valvular atrial fibrillation (NVAF) patients in Shanghai communities, and providing standardized comprehensive management and follow-up, we aim to explore the impact of standardized community management on improving disease awareness, standardizing atrial fibrillation (AF) treatment, reducing the risk of complications occurrence, and addressing risk factors for AF patients. METHODS: This research selected elderly atrial fibrillation patients from Zhuanqiao Community Health Service Center, Minhang District, Shanghai from July 2020 to October 2022. Their personal health records and examination results were reviewed, and the incidence of AF, awareness, medication, and complications were investigated. Age-adjusted Charlson Comorbidity Index (aCCI), CHA2DS2-VASc score, and HAS-BLED score were used to evaluate disease burden, thromboembolic risk, and bleeding risk, respectively. The patients were subjected to standardized community management, and the compliance rate of disease awareness, treatment, resting heart rate, blood pressure, fasting blood glucose, and body mass index (BMI) were assessed at the baseline, 6 months and 1 year after management. RESULTS: A total of 243 NVAF patients were included, with an average aCCI score of (4.5 ± 1.1). Among them, 28% of the patients were aware of their AF, and 18.1% of the patients were aware of the hazards of AF. Of the patients, 11.9% used anticoagulant drugs, including 6.6% and 5.3% for warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), respectively. 7% of patients used antiplatelet drugs. 26.7% of the patients used heart rate control drugs. 10.3% of the patients experienced thromboembolic events, and 0.8% of the patients experienced bleeding events. 93.0% of the patients were at high risk of thromboembolism, and 24.7% of the patients were at high risk of bleeding. Compared with the baseline, there were significant statistical differences (P < 0.001) in disease awareness, awareness of the hazards of AF, use of anticoagulant drugs and heart rate control drugs, and control of risk factors among NVAF patients after standardized community management. Moreover, with the extension of management time, there was a linear increase in the awareness of NVAF, awareness of the hazards of AF, utilization rate of anticoagulant drugs, utilization rate of heart rate control drugs, blood pressure, blood glucose, and BMI compliance rate (P < 0.001). CONCLUSION: Currently, the awareness, treatment, and control of risk factors for AF in elderly NVAF patients in Shanghai community are not satisfactory. Standardized community management helps to improve the diagnosis, treatment, and control of risk factors in AF.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia , Humanos , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/efeitos adversos , Administração Oral , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , China/epidemiologia , Fatores de Risco , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemorragia/epidemiologia , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle
20.
Medicine (Baltimore) ; 102(17): e33684, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37115045

RESUMO

Few studies have explored the association between organizational justice and mental health, particularly in collectivist countries. Hence, the aim of the present study was to evaluate the impact of organizational justice on psychological distress and to discuss the findings in collectivist culture. A cross-sectional survey was conducted among nurses from public hospitals in western of China, July 2022, which followed the STROBE guidelines. This study used Chinese versions of the Organizational Justice Scale and Kesseler Psychological Distress Scale to assess the perceptions of organizational justice and mental health levels, respectively. A total of 663 nurses completed the questionnaires. The psychological distress of university-educated and low-income nurses was poor. There was a moderately positive relationship between organizational justice and psychological distress (R = 0.508, P < .01), indicating that the greater level of organizational injustice, the poorer mental health. Hierarchical regression analysis showed that organizational justice was an strong predictor of psychological distress, accounting for approximately 20.5% of the psychological distress. The findings of this study highlight the importance of interpersonal injustice and distributive injustice on psychological distress specific in Chinese culture, suggesting that nursing management or leaders should notice that the most being taken seriously by nurses is their recognition and respect for subordinate, meanwhile, alerting nurses, in some sense, a negative relationship with leaders as a kind of workplace bullying could harm their mental health. The promulgation of organizational justice policy to protect employees from the government and the real role of employee labor union organizations are urgently needed.


Assuntos
Enfermeiras e Enfermeiros , Cultura Organizacional , Humanos , Estudos Transversais , Justiça Social/psicologia , Inquéritos e Questionários , Hospitais Públicos , Local de Trabalho/psicologia
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