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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 125011, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39213831

RESUMO

Thiols function as antioxidants in food, prolonging shelf life and enhancing flavor. Moreover, thiols are vital biomolecules involved in enzyme activity, cellular signal transduction, and protein folding among critical biological processes. In this paper, the fluorescent probe PYL-NBD was designed and synthesized, which utilized the fluorescent molecule pyrazoline, the lysosome-targeted morpholine moiety, and the sensing moiety NBD. Probe PYL-NBD was tailored for the recognition of biothiols through single-wavelength excitation, yielding distinct fluorescence emission signals: blue for Cys, Hcy, and GSH; green for Cys, Hcy. Probe PYL-NBD exhibited rapid reaction kinetics (<10 min), distinct fluorescence response signals, and low detection limits (15.7 nM for Cys, 14.4 nM for Hcy, and 12.6 nM for GSH). Probe PYL-NBD enabled quantitative determination of Cys content in food samples and L-cysteine capsules. Furthermore, probe PYL-NBD had been successfully applied for confocal imaging with dual-channel detection of biothiols in various biological specimens, including HeLa cells, zebrafish, tumor sections, and Arabidopsis thaliana.


Assuntos
Cisteína , Corantes Fluorescentes , Análise de Alimentos , Glutationa , Lisossomos , Espectrometria de Fluorescência , Peixe-Zebra , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Lisossomos/química , Lisossomos/metabolismo , Células HeLa , Cisteína/análise , Animais , Análise de Alimentos/métodos , Glutationa/análise , Espectrometria de Fluorescência/métodos , Homocisteína/análise , Arabidopsis/química , Limite de Detecção , Microscopia Confocal
2.
Bioorg Chem ; 153: 107862, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39362080

RESUMO

Ergosterol peroxide (EP) is a natural steroid compound that has been reported to have significant antitumor activity. However, its poor water solubility and cellular uptake mean that it has weak efficacy against tumor cells. Herein, we designed and synthesized a series of EP derivatives with mitochondrial targeting properties. Of these, compound 15a showed an IC50 value of 0.32 µM against MCF-7 cells, which was 67-fold higher than that of the parental EP (IC50 = 21.46 µM), and was better than cisplatin (IC50 = 4.23 µM), had a selectivity index of 25.28 (IC50MCF-10A/IC50MCF-7). Additionally, compound 15a promoted an increase in intracellular reactive oxygen species levels and a decrease in mitochondrial membrane potential, and blocked the cell cycle in the G0/G1 phase. In a mouse model of breast cancer, 15a showed 89.85 % tumor inhibition at a dose of 20 mg/kg, which is similar to the therapeutic effect of the cisplatin. On the basis of these results, 15a could be considered for further preclinical evaluation for cancer therapy.

3.
Front Endocrinol (Lausanne) ; 15: 1426781, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39371931

RESUMO

In the clinical diagnosis and treatment of pituitary adenomas, MRI plays a crucial role. However, traditional manual interpretations are plagued by inter-observer variability and limitations in recognizing details. Radiomics, based on MRI, facilitates quantitative analysis by extracting high-throughput data from images. This approach elucidates correlations between imaging features and pituitary tumor characteristics, thereby establishing imaging biomarkers. Recent studies have demonstrated the extensive application of radiomics in differential diagnosis, subtype identification, consistency evaluation, invasiveness assessment, and treatment response in pituitary adenomas. This review succinctly presents the general workflow of radiomics, reviews pertinent literature with a summary table, and provides a comparative analysis with traditional methods. We further elucidate the connections between radiological features and biological findings in the field of pituitary adenoma. While promising, the clinical application of radiomics still has a considerable distance to traverse, considering the issues with reproducibility of imaging features and the significant heterogeneity in pituitary adenoma patients.


Assuntos
Adenoma , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Adenoma/diagnóstico por imagem , Adenoma/patologia , Imageamento por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Radiômica
5.
Bioorg Med Chem ; 113: 117934, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39369566

RESUMO

Lupeol is a natural pentacyclic triterpenoid with a wide range of biological activities. To improve the water solubility and targeting of lupeol, in the following study, we synthesized 27 lupeol derivatives in the first series by introducing lipophilic cations with lupeol as the lead compound. Through the screening of different cancer cells, we found that some of the derivatives showed better activity than cisplatin against human non-small cell lung cancer A549 cells, among which compound 6c was found to have an IC50 value of 1.83 µM and a selectivity index of 21.02 (IC50MRC-5/IC50A549) against A549 cells. To further improve the antiproliferative activity of the compounds, we replaced the ester linkage of the linker with a carbamate linkage and synthesized a second series of five lupeol derivatives which were screened for activity, among which compound 14f was found to have an IC50 value of 1.36 µM and a selectivity index of 15.60 (IC50MRC-5/IC50A549) against A549 cells. We further evaluated the bioactivity of compounds 6c and 14f and found that both compounds induced apoptosis in A549 cells, promoted an increase in intracellular reactive oxygen species and decrease in mitochondrial membrane potential, and inhibited the cell cycle in the S phase. Of the compounds, compound 14f showed stronger bioactivity than compound 6c. We then selected compound 14f for molecular-level Western blot evaluation and in vivo evaluation in the zebrafish xenograft A549 tumor cell model. Compound 14f was found to significantly downregulate Bcl-2 protein expression and upregulate Bax, Cyt C, cleaved caspase-9, and cleaved caspase-3 protein expression, and 14f was found to be able to inhibit the proliferation of A549 cells in the zebrafish xenograft model. The above results suggest that compound 14f has great potential in the development of antitumor drugs targeting mitochondria.

6.
Zhongguo Zhen Jiu ; 44(9): 1062-6, 2024 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-39318298

RESUMO

The paper summarizes Professor JI Laixi's academic thought on acupuncture and moxibustion. Professor JI Laixi inherits and carries forward the theory and technical system of Shanxi "new nine needles", deepens its academic connotation, and promotes clinical practice. He advocates the integration of Chinese and western medicine, and the inclusion of multiple disciplines, e.g. acupuncture and moxibustion of Chinese medicine and modern anatomy. He takes the lead in proposing a new approach to the treatment of meridian diseases of limbs, "treating the neck region for the diseases of head, treating the abdominal region for the diseases of the lumbar region, and treating the lumbar region for the disease of knees". He proposes the acupoint prescription being standardized and simplified, explores the system of acupoint prescription and establishes the prescriptions for gastric diseases, intestinal diseases and antihypertension.


Assuntos
Terapia por Acupuntura , Moxibustão , Moxibustão/história , Moxibustão/métodos , Humanos , Terapia por Acupuntura/história , China , História do Século XX , Acupuntura/educação , Acupuntura/história , Pontos de Acupuntura
7.
Zhen Ci Yan Jiu ; 49(8): 836-844, 2024 Aug 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39318313

RESUMO

OBJECTIVES: To observe the effect of moxibustion with seed-size moxa cones on the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor-κB(NF-κB) signaling pathway in mice with ulcerative colitis(UC), so as to explore the therapeutic mechanism of moxibustion with seed-size moxa cones on colonic injury in UC. METHODS: Forty male C57BL/6 mice were randomly divided into blank group, model group, moxibustion group, and western medicine group, with 10 mice in each group. The UC mouse model was established by 3% DSS solution by free drinking for 7 consecutive days. Mice in the moxibustion group were treated with seed-size moxa cones at "Zhongwan"(CV12), "Tianshu"(ST25) and "Shangjuxu"(ST37), 3 moxa cones per point, with each cone applied for approximately 30 s, while mice in the western medicine group were orally administered with 300 mg/kg mesalazine solution, which were both conducted once a day for 7 consecutive days. The general condition of mice was observed every 2 days, and the disease activity index (DAI) score was calculated. HE staining was used to observe the morphology of colonic tissue in mice. ELISA was used to detect the serum interleukin(IL)-1ß, tumor necrosis factor(TNF)-α, IL-6, and IL-8 contents. Immunohistochemistry was used to detect the positive expression of TLR4 and MyD88 in colonic tissue of mice. Real-time fluorescence quantitative PCR was used to detect the expression levels of TLR4, MyD88, and NF-κB p65 mRNAs in colonic tissue. RESULTS: Compared with the blank group, varying degrees of soft or watery stools were observed, colon length and body weight were decreased(P<0.01) in mice of the model group, while DAI score, colon weight index, mucosal damage score, colonic pathological score, serum IL-1ß, TNF-α, IL-6, and IL-8 contents, positive expressions of TLR4 and MyD88, and TLR4, MyD88, and NF-κB p65 mRNA expressions in colonic tissue were increased(P<0.01). Compared with the model group, improved fecal characteristics were observed, colon length and body weight were increased(P<0.01) in mice of the moxibustion group and western medicine group, while DAI scores, colon weight indexes, mucosal damage scores, colonic pathological score, serum contents of IL-1ß, TNF-α, IL-6, and IL-8, positive expressions of TLR4 and MyD88, and TLR4, MyD88, and NF-κB p65 mRNA expressions in colonic tissue were decreased(P<0.01, P<0.05). There was no significant difference in the above indicators between the moxibustion group and the western medicine group. CONCLUSIONS: Moxibustion with seed-size moxa cones may alleviate colonic injury in UC mice by regulating the TLR4/MyD88/NF-κB signaling pathway and reducing the release of inflammatory factors.


Assuntos
Colite Ulcerativa , Colo , Camundongos Endogâmicos C57BL , Moxibustão , Fator 88 de Diferenciação Mieloide , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Camundongos , Masculino , Humanos , Colite Ulcerativa/terapia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/genética , NF-kappa B/metabolismo , NF-kappa B/genética , Colo/metabolismo , Modelos Animais de Doenças , Hordeum/química
8.
Biomater Res ; 28: 0079, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39296854

RESUMO

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen species and inflammatory response contribute to secondary damage following ischemic insult. Nanozymes with robust anti-oxidative stress properties possess therapeutic possibility for ischemic insult. However, insufficiency of nanozyme accumulation in the neuronal mitochondria hindered their application. Herein, we constructed polydopamine-coated Prussian blue nanoparticles (PB@PDA NPs) to realize the targeting neuronal mitochondria for ischemic stroke, with the properties of antioxidant and anti-inflammation. After administration, much higher accumulation of PB@PDA NPs in the brain was observed compared to that in the PB NP group. Moreover, PB@PDA NPs effectively attenuated brain infarct than that of PB NPs in neonatal mice following hypoxia-ischemia (HI) insult. PB@PDA NPs mainly colocated with neuronal mitochondria in vivo and in vitro. Apart from attenuating oxidative stress, PB@PDA NPs also suppressed neuronal apoptosis and counteracted inflammation, which effectively promote a short- and long-term functional recovery in HI mice. Further, the therapeutic efficacy of PB@PDA NPs was also found in adult ischemic mice via tail vein injection. Collectively, these findings illustrate that PB@PDA NPs via system injection accumulate in neuronal mitochondria and are beneficial for ischemic stroke.

9.
Heliyon ; 10(17): e36664, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39286182

RESUMO

Acupuncture is an integral component of complementary and alternative medicine that has been reported to enhance sperm motility, improve semen quality, and consequently augment male fertility. However, the precise mechanisms of action and the underlying molecular pathways remain unclear. In the present study, we aimed to elucidate the potential mechanisms through which acupuncture improves reproductive function in a mouse model of cyclophosphamide-induced asthenozoospermia. We collected sperm from the epididymis for semen analysis, collected serum to determine gonadotropin and oxidative stress marker levels, conducted histological examination of testicular tissue using hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and observed mitochondrial morphology using transmission electron microscopy (TEM). We also assessed oxidative stress levels and total iron content in testicular tissue and validated the proteomic and transcriptomic analysis results of testicular tissue using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), protein imprinting analysis, and immunohistochemistry (IHC). Our results indicate that acupuncture enhances sperm quality in asthenozoospermic mice; increases serum testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; and attenuates oxidative damage, iron accumulation, and mitochondrial injury in mouse testicular tissues. Through protein and transcriptomic analyses, we identified 21 key genes, of which cytochrome b-245 heavy chain (CYBB), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 1 (ACSL1), and ferritin mitochondria (FTMT) were closely associated with ferroptosis. RT-qPCR, protein imprinting, and immunofluorescence (IF) analyses collectively indicated that acupuncture reduced ACSL1 and CYBB expression, and increased GPX4 and FTMT expression. Overall, the ferroptosis pathway associated with ACSL1/CYBB/FTMT/GPX4 represents a potential strategy through which acupuncture can improve the reproductive function in asthenozoospermic mice.

10.
Adv Mater ; : e2409400, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39267457

RESUMO

Osteochondral injury is a prevalent condition for which no specific treatment is currently available. This study presents a piezoelectric-conductive scaffold composed of a piezoelectric cartilage-decellularized extracellular matrix (dECM) and piezoelectric-conductive modified gelatin (Gel-PC). The piezoelectricity of the scaffold is achieved through the modification of diphenylalanine (FF) assembly on the pore surface, while the conductive properties of scaffold are achieved by the incorporating poly(3,4-ethylenedioxythiophene). In vitro experiments demonstrate that bone marrow mesenchymal stem cells (BMSCs) undergo biphasic division during differentiation. In vivo studies using a Parma pig model of osteochondral defects demonstrate that the piezoelectric-conductive scaffold exhibits superior reparative efficacy. Notably, the generation of electrical stimulation is linked to joint movement. During joint activity, mechanical forces compress the scaffold, leading to deformation and the subsequent generation of an electric potential difference. The positive charges accumulated on the upper layer of the scaffold attract BMSCs, promoting their migration to the upper layer and chondrogenic differentiation. Meanwhile, the negative charges in the lower layer induce the osteogenic differentiation of BMSCs. Overall, this piezoelectric-conducive scaffold provides a promising platform for the effective repair of osteochondral defects.

11.
Cell Biochem Biophys ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237779

RESUMO

Cancer-associated fibroblasts (CAFs) represent one of the major components of the tumor stroma, which might create an immunosuppressive tumor microenvironment by inducing and functionally polarizing protumoral macrophages. Previous studies indicated that exosomes derived from CAFs might transmit regulating signals and boost esophageal squamous cell carcinoma (ESCC) development. This study is designed to explore the role and mechanism of CAFs-derived exosomal microRNA-889-3p (miR-889-3p) in ESCC progression. Macrophage polarization was detected using flow cytometry. miR-889-3p, Tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (iNOS) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, cycle progression, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), scratch assay, and Transwell assays. α-SMA, FAP, CD63, CD81, and signal transducer and activator of transcription 1 (STAT1) protein levels were detected using western blot. Exosomes were characterized using an electron microscope and nanoparticle tracking analysis (NTA). Binding between miR-889-3p and STAT1 was predicted by Starbase, and verified by a dual-luciferase reporter and RNA pull-down. The effect of CAFs-derived exosomal miR-889-3p on ESCC tumor growth in vivo was detected using mice xenograft assay. miR-889-3p level was decreased in LPS-induced M0 macrophages. CAF-derived exosomal miR-889-3p knockdown suppressed ESCC proliferation, migration, and invasion. CAFs might transfer miR-889-3p to M0 macrophages via exosomes. STAT1 was a target of miR-889-3p. Besides, in vivo studies confirmed that CAFs-derived exosomal miR-889-3p can accelerate ESCC tumor growth by regulating STAT1. CAFs-derived exosomal miR-889-3p facilitates esophageal squamous cell carcinoma cell proliferation, migration, and invasion by inhibiting M1 macrophage polarization through down-regulation of STAT1, providing a promising therapeutic target for ESCC.

12.
Ying Yong Sheng Tai Xue Bao ; 35(7): 1935-1943, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39233423

RESUMO

Understanding the responses of ecosystem service trade-offs and synergies in metropolitan areas to the multidimensional expansion of urban space is of great significance for the optimization of regional land spatial pattern and high-quality development. With the Guangfo Metropolitan Area as research region, we used land use data and natural ecological environment data from 2000 to 2020 to measure the expansion characteristics of urban space in the dimensions of scale, distribution, and morphology by using the landscape pattern indices. We further calculated four main ecosystem services: urban cooling, habitat quality, recreation, and water conservation by the InVEST model, quantified the trade-off and synergistic relationship of multiple ecosystem services by the coupling coordination degree model, and explored its response to multidimensional urban spatial expansion by using the multi-scale geographically weighted regression model. The results showed that urban land use scale in the Guangfo Metropolitan Area continued to increase from 2000 to 2020, with an accelerated growth rate from 2010 to 2020. The ave-rage patch area of urban land in the central area and the urban land of small patches in the northeast increased, evolving from a "dual-center" structure to a "single-center" one. The distance between urban land patches in the Guangfo Metropolitan Area was relatively small, indicating a compact distribution of urban land. The distance between newly developed urban land patches was also small, but had gradually increased in recent years. The patch shape of urban land was relatively regular and less complex, but the complexity of the newly added urban land gra-dually increased. The ecosystem service trade-offs and synergies in the Guangfo Metropolitan Area had undergone significant changes, with a decrease in synergies and an increase in trade-off, and extreme trade-offs had gradually become dominant. The response of ecosystem services synergies to changes in urban land use scale was the most intense and had spatial heterogeneity, while the response to the change of distribution and morphological characte-ristics of urban land showed periodic differences.


Assuntos
Cidades , Conservação dos Recursos Naturais , Ecossistema , China , Planejamento de Cidades , Urbanização , Monitoramento Ambiental/métodos , Modelos Teóricos
13.
Heliyon ; 10(16): e35867, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39220995

RESUMO

Purpose: To assess the quantitative gray matter volume of the limbic system in growth hormone-secreting pituitary adenoma (GHPAs) patients and its correlation to cognitive function. Method: 91 right-handed patients with pituitary adenomas were retrospectively included from the First Affiliated Hospital of Sun Yat-sen University -48 with GHPAs and 43 with non-functioning pituitary adenomas (NFPAs). Participants underwent serum hormone assessment, regular sellar MRI scanning with T1WI-MPRAGE. Cognitive function was gauged using MoCA and MMSE. Brain region auto-segmentation and gray matter volume calculation were conducted on the Brainsite platform. Results: Compared to NFPAs patients, GHPAs patients had higher gray matter volume (758,285 vs 674,610 mm³, p < 0.001). No significant volumetric differences in both sides of limbic system gray matter while there were evident differences in the relative volumes of limbic system gray matter between groups. GHPAs patients scored lower on MOCA (24.0 (2.18) vs 25.1 (2.28), p < 0.031), with no difference in MMSE. We observed a significant correlation between the relative limbic volume and MOCA scales, while no evident correlation was found between relative limbic volume and serum hormone or tumor aggressiveness. Univariate and multivariate Logistic regression showed that hippocampus and limbic cortex (parahippocampal gyrus and internal olfactory area) of advantageous hemisphere correlated significantly with occurrence of mild cognitive impairment with the C-statistic reaching 0.90. Conclusion: Patients with GHPAs show a relative decrease in limbic gray matter volume, especially in the hippocampus and limbic cortex of the dominant hemisphere, which is associated with mild cognitive impairment.

14.
Anal Chem ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39282891

RESUMO

Herein, CuS colloidal nanocrystals (NCs) with adjustable band gap and good film forming ability have been synthesized as new ECL materials. Furthermore, the band gap and oxygen vacancy (OV) content of CuS NCs are regulated by Al3+ doping, which significantly improves the ECL response of CuS NCs. First, the band gap of CuS-Al NCs decreases after doping with Al3+, which makes it easier for electrons to transition across the band gap. At the same time, the oxygen vacancy of CuS-Al NCs increases, which is conducive to improving the conductivity and promoting charge transfer, thus improving the ECL performance of CuS-Al NCs. Circulating tumor DNA (ctDNA) is an important tumor marker, and its sensitive monitoring is of great significance for tumor diagnosis, treatment, and prognosis detection. Therefore, an ECL biosensor for ultrasensitive detection of circulating tumor DNA (ctDNA) was prepared by using CuS-Al NCs as luminescent material and combining multiple antidromic hybrid chain reaction (anti-HCR) strategy mediated by the target. Compared with the process of target-induced HCR generation, this strategy first forms multiple HCR products and then destroys the already formed HCR products by target-induced destruction, which enhances the sensitivity of target response and improves the reaction efficiency. The constructed biosensor has good detection performance, and the detection limit is as low as 2.74 aM. This work puts forward the luminescence phenomenon of colloidal nanocrystals as new ECL materials, which broadens the application of ECL technology in ultrasensitive biochemical detection.

15.
Molecules ; 29(18)2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39339370

RESUMO

In this study, novel ergosterol peroxide (EP) derivatives were synthesized and evaluated to assess their antiproliferative activity against four human cancer cell lines (A549, HepG2, MCF-7, and MDA-MB-231). Compound 3g exhibited the most potent antiproliferative activity, with an IC50 value of 3.20 µM against MDA-MB-231. This value was 5.4-fold higher than that of the parental EP. Bioassay optimization further identified 3g as a novel glutaminase 1 (GLS1) inhibitor (IC50 = 3.77 µM). In MDA-MB-231 cells, 3g reduced the cellular glutamate levels by blocking the glutamine hydrolysis pathway, which triggered reactive oxygen species production and induced caspase-dependent apoptosis. Molecular docking indicated that 3g interacts with the reaction site of the variable binding pocket by forming multiple interactions with GLS1. In a mouse model of breast cancer, 3g showed remarkable therapeutic effects at a dose of 50 mg/kg, with no apparent toxicity. Based on these results, 3g could be further evaluated as a novel GLS1 inhibitor for triple-negative breast cancer (TNBC) therapy.


Assuntos
Antineoplásicos , Proliferação de Células , Ergosterol , Glutaminase , Simulação de Acoplamento Molecular , Neoplasias de Mama Triplo Negativas , Humanos , Glutaminase/antagonistas & inibidores , Glutaminase/metabolismo , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/farmacologia , Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Ensaios Antitumorais Modelo de Xenoenxerto , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
16.
Anal Bioanal Chem ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39191938

RESUMO

Biothiols, characterized by their unique sulfhydryl (-SH) groups, possess excellent antioxidant properties, effectively neutralizing the damage to cellular structures caused by reactive oxygen species (ROS) in living organisms. Additionally, lysosomes play a crucial role in decomposing damaged biomolecules through the action of their internal enzymes, regulating the cellular redox state, and mitigating oxidative stress. To facilitate rapid monitoring of intracellular biothiols, particularly within lysosomes, we constructed a lysosome-targeted biothiol fluorescent probe, PHL-DNP, in this study. PHL-DNP exhibited excellent photophysical properties in an aqueous test system, including strong fluorescence enhancement response, excellent selectivity, and low detection limits (Cys 16.5 nM, Hcy 16.8 nM, GSH 21.3 nM, Cap 26.6 nM). These attributes enabled easy and efficient qualification of Cys on test strips and accurate determination of the effective content of captopril tablets. Notably, PHL-DNP demonstrated low cytotoxicity and precise lysosomal targeting. Through bioimaging, PHL-DNP not only monitored changes in biothiol levels under oxidative stress but also assessed biothiols in complex biological systems such as live HeLa cells, zebrafish, tumor tissue sections, and radish roots. This provides a promising tool for quantitative analysis of biothiols, disease marker detection, and drug testing.

17.
Nutrients ; 16(16)2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39203923

RESUMO

(1) Background: Although daily time-use is associated with diet quality and cardiorespiratory fitness (CRF) in children, their interdependence remains unexplored. This study first examined the associations between reallocating daily movement time and diet quality and CRF, and second the mediating role of diet quality in the relationship between daily time-use and CRF. (2) Methods: This study included 1131 Chinese children (aged 8 to 10 years; median [interquartile range]: 8.5 [8.3, 8.8]) at baseline (September 2022) and 1268 children at the 9-month follow-up (June 2023) from the OptiChild study. Daily durations of moderate-to-vigorous physical activity (MVPA), sleep, and sedentary behavior (e.g., screen time) were self-reported or proxy-reported by parents. Diet quality was assessed via the Diet Quality Questionnaire (DQQ), which uses a 24 h dietary recall and is categorized according to the Global Dietary Recommendations (GDR) score and Food Group Diversity Score (FGDS). The CRF was measured using VO2max after the 20 m shuttle run test. Longitudinal associations between daily time-use, diet quality, and CRF were calculated using isotemporal substitution models. Mediation analyses were used to determine whether diet quality mediated the associations between daily time-use and CRF. (3) Results: Reallocation of 30 min from screen time to MVPA resulted in significant improvements in the GDR score (ß baseline = 0.11, p = 0.024; ß follow-up = 0.26, p < 0.001), FGDS (ß baseline = 0.11, p = 0.006; ß follow-up = 0.19, p < 0.001), and CRF (ß baseline = 0.40, p < 0.001; ß follow-up = 0.26, p = 0.001). Diet quality partially mediated the associations between MVPA, screen time, and CRF. Substituting 30 min of screen time for MVPA led to diet quality mediating a proportion of the association with CRF (GDR score: 11.4%, FGDS: 6.6%). (4) Conclusions: These findings underscore the importance of optimizing daily time-use of MVPA and screen time and improving diet quality to promote physical fitness in school-aged children.


Assuntos
Aptidão Cardiorrespiratória , Dieta , Exercício Físico , Comportamento Sedentário , Humanos , Criança , Masculino , Feminino , Análise de Mediação , Fatores de Tempo , Sono/fisiologia , Tempo de Tela , China , Dieta Saudável
18.
Acta Trop ; 258: 107355, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39122103

RESUMO

Migratory birds play an important role in the cross-regional transmission of zoonotic pathogens. Assessing the presence of zoonotic pathogens carried by migratory birds is critical for disease control. However, information about Blastocystis infection in the migratory birds is very limited. Thus, we conducted this study with the aim to explore the occurrence, prevalence and subtyping of Blastocystis in four breeds of migratory birds in northeastern China. From October 2022 to April 2023, a total of 427 fresh fecal samples were obtained from four breeds of migratory birds in five nature reserves in northeastern China, and screened for Blastocystis by PCR amplification. Twenty-one (4.92 %) of the studied samples were confirmed Blastocystis-positive, and two known zoonotic subtypes ST6 and ST7 were founded, with ST7 being the major subtype. Until now, we firstly reported the infection status and subtyping of Blastocystis in the migratory Greater White-Fronted Goose, White Stork, Oriental White Stork and Bean Goose in China. More importantly, these findings present further data on the genetic diversity and transmission routes of Blastocystis and further arouse public health concerns about this organism.


Assuntos
Migração Animal , Doenças das Aves , Aves , Infecções por Blastocystis , Blastocystis , Fezes , Animais , Blastocystis/genética , Blastocystis/classificação , Blastocystis/isolamento & purificação , China/epidemiologia , Infecções por Blastocystis/veterinária , Infecções por Blastocystis/epidemiologia , Infecções por Blastocystis/parasitologia , Doenças das Aves/parasitologia , Doenças das Aves/epidemiologia , Aves/parasitologia , Fezes/parasitologia , Prevalência , Filogenia , Variação Genética , Reação em Cadeia da Polimerase , DNA de Protozoário/genética
19.
Molecules ; 29(16)2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39202985

RESUMO

The equilibrium state of hydrogen sulfide (H2S), a gaseous signaling molecule produced by lysosomal metabolites, in vivo is crucial for cellular function. Abnormal fluctuations in H2S concentration can interfere with the normal function of lysosomes, which has been closely linked to the pathogenesis of a variety of diseases. In view of this, a novel fluorescent probe Lyso-DPP based on 1,3,5-triarylpyrazolines was developed for the precise detection of H2S in lysosomes by using the hydrophilic morpholine moiety as a lysosomal targeting unit, and 2,4-dinitroanisole as a fluorescence-quenching and H2S-responsive unit. The probe cleverly combines the advantages of simple synthesis, sensitive blue fluorescence turn-on with a limit of detection, LOD, of 97.3 nM, good stability, and fast response time (10 min), which makes Lyso-DPP successful in portable monitoring of meat freshness in the form of test strips. Moreover, the excellent biocompatibility and precise targeting capability of the probe Lyso-DPP make it perform well in the monitoring of H2S in lysosomes, living cells, and zebrafish. This work not only provides new technical tools for food quality control but also paves up new ideas for early diagnosis and treatment of H2S-related diseases.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio , Lisossomos , Peixe-Zebra , Sulfeto de Hidrogênio/análise , Lisossomos/metabolismo , Corantes Fluorescentes/química , Humanos , Animais , Inocuidade dos Alimentos , Imagem Óptica/métodos , Limite de Detecção
20.
Heliyon ; 10(14): e34536, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39148980

RESUMO

Background: Mycobacterium abscessus (M. abscessus) infection is rare in children who were previously healthy, particularly in infants. We present the first report of a family outbreak of M. abscessus infection among immunocompetent infant triplets. Methods: We reviewed triplets' demographic data, laboratory tests and imaging examinations to describe their clinical features. We performed whole-exome sequencing to rule out primary immunodeficiency disorders. We used DNA sequencing for M. abscessus subspecies identification. Results: The fraternal triplets (triples A, B and C) presented with a 10-day history of cough. Triple A also experienced a brief episode of fever, and triple B had tachypnea. Chest CT scans showed pulmonary masses and nodules in triples A and C, and cavities in triple B. Cultures of sputum and bronchoalveolar lavage fluid from all triplets yielded M. abscessus. Further subspecies identification showed that isolates from triples A and C were M. abscessus subsp. massiliense, and isolates from triple B were M. abscessus subsp. abscessus (MAA). After eight months of combination therapy, the pulmonary lesions of the triplets improved significantly. Conclusion: Our study confirms that M. abscessus pulmonary disease can occur in immunocompetent infants. We hypothesize that the simultaneous infection of the triplets may be associated with their prematurity and extensive environmental exposure. This study highlights the importance to include M. abscessus infection in the differential diagnosis of pulmonary masses and/or cavities, regardless of the age of onset or the presence of underlying pathology or susceptible genes.

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