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1.
Adv Healthc Mater ; : e2402063, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39380347

RESUMO

Tumor microenvironment, characterized by dense extracellular matrix and severe hypoxia, has caused pronounced resistance to photodynamic therapy (PDT). Herein, it has designed an artificial nitric oxide (NO) nanotractor with a unique "motor-cargo" structure, where a photoswitching upconversion nanoparticle (UCNP) core serves as the optical engine to harvest NIR light and asymmetrically coated mesoporous silica (SiO2) shell acts as a cargo unit to load nitric oxide (NO) fuel molecule (RBS, Roussin's black salt) and PDT photosensitizer (ZnPc, zinc phthalocyanine). Upon illumination by 980 nm light, the UCNP emits blue light to excite RBS salt and release NO gas. On one hand, NO is used as the driving force to propel the particle with a high speed of ≈194 µm s-1 that generates significant rupture stress (over 0.95 kPa) on cell membrane to promote cellular endocytosis and intratumoral penetration. On the other hand, NO enables to alleviate tumor hypoxia by inhibiting cellular respiration as an oxygen conserver. When the excitation is subsequently switched to 808 nm light, the UCNP emits red light, triggering ZnPc to produce large amount of reactive oxygen species for PDT treatment. This study explores Janus-typed nanostructures for cell-particle interaction and gas-assisted phototherapy, opening avenues for versatile bioapplications.

2.
J Fluoresc ; 2024 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-39425836

RESUMO

Construction of efficient chemosensors for highly specific and sensitive detection of mercury ions remains a great challenge. In this work a highly selective and sensitive probe CY was designed and synthesized by using coumarin fluorophore as the matrix and thioacetal moiety as the reactive recognition site for Hg2+. By virtue of the thiophilicity of Hg2+, probe CL could be hydrolyzed to deprotect and the thioacetal was transformed to the acyl group after the addition of Hg2+, the blue-green fluorescence was quenched and meanwhile the solution changed from light green to yellow. The detection limit of probe CY for Hg2+ was as low as 6.8 nM, and it could completely react with Hg2+ within 3 min. Moreover, probe CY exhibited good resistance against interference from competitive metal ions and biothiols, high stability in pH 1-11 and applicability for fluorogenic and chromogenic dual-modal detection of Hg2+ in real water samples over a broad range of pH 5-10.

3.
J Ovarian Res ; 17(1): 206, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39425131

RESUMO

OBJECTIVE: To establish a rat model of pharmacological ovariectomy by GnRH-a injection and to preliminarily investigate the reproductive endocrine effects of Xiangshao granules on pharmacologically ovariectomized rats. METHODS: A rat model of pharmacological ovariectomy was established by injecting female rats with Gonadotropin-releasing hormone agonist(GnRH-a).The rats were randomly divided into four groups: GnRH-a injected saline group (GnRH-a + NS); GnRH-a injected oestradiol group (GnRH-a + E2); GnRH-a injected Xiangshao granule group (GnRH-a + Xiangshao), and the control group of saline-injected rats (NS + NS). The number of rats per group was 6.According to observations of the rats' vaginal smears, modelling was determined as successful. Then corresponding drug gavage intervention was administered for 28 days, and rat body weight and anal temperature were measured every other day to adjust the drug intervention amount according to body weight changes. Plasma sex hormone levels (E2, FSH, LH), uterine weight, uterine index and endometrial histomorphological changes, ovarian weight, and ovarian index and ovarian histomorphological changes were measured in each group after the gavage. RESULTS: (1) Plasma sex hormone levels (E2, FSH, LH) of the GnRH-a + NS, GnRH-a + E2, and GnRH-a + Xiangshao granule groups were significantly lower than the NS + NS group (P < 0.001), while the E2 level of the GnRH-a + E2 group was higher than that of the GnRH-a + Xiangshao granule group (P < 0.05). The FSH level of the GnRH-a + E2 group was significantly lower than that of the GnRH-a + Xiangshao granule group (P < 0.05). The LH level of the GnRH-a + E2 group was significantly lower than those in the GnRH-a + NS and GnRH-a + Xiangshao granule groups (P < 0.001, P = 0.001). The LH and FSH levels of the GnRH-a + NS and GnRH-a + Xiangshao granule groups were not significantly different (P > 0.05). (2) Compared with the NS + NS group, the uterine weight and uterine index, and ovarian weight and ovarian index of GnRH-a injected rats in each model all significantly decreased (P < 0.001). Between the groups, the uterine weight and uterine index, and ovarian weight and ovarian index of GnRH-a + E2 and GnRH-a + Xiangshao granule groups were all significantly higher than those of the GnRH-a + NS group (P < 0.001, P < 0.05). The uterine weight and uterine index, and ovarian weight and ovarian index of the GnRH-a + E2 group increased compared with the GnRH-a + Xiangshao granule group (P < 0.05). (3) Compared with the NS + NS group, the number of primordial follicles of the GnRH-a + NS, GnRH-a + E2, and GnRH-a + Xiangshao granule groups increased significantly and the number of growing follicles and mature follicles significantly decreased. (4) Rats' uterine wall of the NS + NS and various GnRH-a groups was significantly thinner, with the endothelial layer atrophied, while the uterine wall of the GnRH-a + E2 and GnRH-a + Xiangshao granule groups was thicker obviously, with the number of vaginal folds and blood vessels also increasing. Specifically, the uterus and vagina improvements in the GnRH-a + E2 group were more obvious than in GnRH-a + NS and GnRH-a + Xiangshao granule groups. CONCLUSION: GnRH-a injection can reduce the levels of sex hormones E2, FSH, and LH in rats, causing perimenopausal symptoms such as hot flashes, while Xiangshao and E2 granules could significantly improve such symptoms and exert a slight oestrogenic effect, to a lesser extent than E2 does. TRIAL REGISTRATION: Not applicable.


Assuntos
Medicamentos de Ervas Chinesas , Hormônio Liberador de Gonadotropina , Ovariectomia , Ovário , Animais , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Útero/efeitos dos fármacos , Hormônio Luteinizante/sangue , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Ratos Sprague-Dawley , Reprodução/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos
4.
Magn Reson Med ; 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39428676

RESUMO

PURPOSE: To investigate the feasibility of rapid CEST MRI acquisition for evaluating oxidative phosphorylation (OXPHOS) in human skeletal muscle at 3T, utilizing ultrafast Z-spectroscopy (UFZ) combined with MRI and the Polynomial and Lorentzian line-shape Fitting (PLOF) technique. METHODS: UFZ MRI on muscle was evaluated with turbo spin echo (TSE) and 3D EPI readouts. Five healthy subjects performed in-magnet plantar flexion exercise (PFE) and subsequent changes of amide, PCr, and partial PCr mixed Cr (Cr+) CEST dynamic signals post-exercise were enabled by PLOF fitting. PCr/Cr CEST signal was further refined through pH correction by using the ratios between PCr/Cr and amide signals, named PCAR/CAR, respectively. RESULTS: UFZ MRI with TSE readout significantly reduces acquisition time, achieving a temporal resolution of <50 s for collecting high-resolution Z-spectra. Following PFE, the recovery/decay times (τ) for both PCr and Cr in the gastrocnemius muscle of the calf were notably longer when determined using PCr/Cr CEST compared to those after pH correction with amideCEST, namely τ Cr + $$ {\tau}_{Cr^{+}} $$ = 87.1 ± 15.8 s and τ PCr $$ {\tau}_{PCr} $$ = 98.1 ± 20.4 s versus τ CAR $$ {\tau}_{CAR} $$ = 32.9 ± 19.7 s and τ PCAR $$ {\tau}_{PCAR} $$ = 43.0 ± 13.0 s, respectively. τ PCr $$ {\tau}_{PCr} $$ obtained via 31P MRS ( τ PCr $$ {\tau}_{PCr} $$ = 50.3 ± 6.2 s) closely resemble those obtained from pH-corrected PCr/Cr CEST signals. CONCLUSION: The outcomes suggest potential of UFZ MRI as a robust tool for non-invasive assessment of mitochondrial function in skeletal muscles. pH correction is critical for the reliable OXPHOS measurement by CEST.

5.
Phytomedicine ; 134: 155995, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39270591

RESUMO

BACKGROUND: Instead of completely suppressing blood vessels inside tumors, vascular normalization therapy is proposed to normalize and prune the abnormal vasculature in tumor microenvironment (TME) to acquire a normal and stable blood flow and perfusion. The theoretical basis for the use of "blood-activating and stasis-resolving" formulas in Traditional Chinese Medicine to treat cancer is highly consistent with the principle of vascular normalization therapy, suggesting the potential application of these traditional formulas in vascular normalization therapy. PURPOSE: To study the underlying mechanisms of a classical "blood-activating and stasis-resolving" formula, Taohong Siwu decoction (TSD), in enhancing the efficacy of chemotherapy for breast cancer treatment. STUDY DESIGN: HUVECs and transgenic zebrafish embryos were used as the major model in vitro. A 4T1 mouse breast cancer model was applied to study tumor vasculature normalization of TSD and the combination effects with DOX. RESULTS: Our data showed that TSD exhibited anti-angiogenic potential in HUVECs and transgenic zebrafish embryos. After 20 days treatment, TSD significantly normalized the tumor vasculature by remodeling vessel structure, reducing intratumoral hypoxia and vessel leakage, and promoting vessel maturation and blood perfusion in 4T1 breast tumor-bearing mice. Moreover, the anti-tumor efficacy of doxorubicin liposome in 4T1 breast tumors was significantly improved by TSD, including the suppression of tumor cell proliferation, angiogenesis, hypoxia, and the increase of cell apoptosis, which is likely through the vascular normalization induced by TSD. TSD also shifted the macrophage polarization from M2 to M1 phenotype in TME during the combination therapy, as evidenced by the reduced number of CD206+ macrophages and increased number of CD86+ macrophages. Additionally, TSD treatment protected against doxorubicin-induced cardiotoxicity in animals, as evidenced by the reduced cardiomyocytes apoptosis and improved heart function. CONCLUSION: This study demonstrated for the first time that TSD as a classical Chinese formula can enhance the drug efficacy and reduce the side effects of doxorubicin. These findings can support that TSD could be used as an adjuvant therapy in combination with conventional chemotherapy for the future breast cancer treatment.


Assuntos
Doxorrubicina , Medicamentos de Ervas Chinesas , Células Endoteliais da Veia Umbilical Humana , Neovascularização Patológica , Peixe-Zebra , Animais , Doxorrubicina/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Feminino , Camundongos , Neovascularização Patológica/tratamento farmacológico , Camundongos Endogâmicos BALB C , Animais Geneticamente Modificados , Microambiente Tumoral/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos
6.
World J Clin Oncol ; 15(8): 961-964, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39193158

RESUMO

Gastrointestinal cancer (GIC) is a common and widespread form of tumor, with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions. However, many patients are already in the late stages when first diagnosed with such cancer, resulting in a poor prognosis. Thus, it is necessary to explore new methods and research directions in order to improve the treatment of GIC. Given the specific nature of the gastrointestinal tract, research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells. Interestingly, six transmembrane epithelial antigens of the prostates (STEAPs) have been found to be significantly linked to the progression of malignant tumors, associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function. This paper explores the mechanism of STEAPs in the inflammatory response of GIC, providing a theoretical basis for the prevention and early intervention of GIC. The basic properties of the STEAP family as metal reductase are also explained. When it comes to intervention for GIC prevention, STEAPs can affect the activity of Fe3+, Cu2+ reductase and regulate metal ion uptake in vivo, participating in inflammation-related iron and copper homeostasis. Thus, the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.

7.
Nat Commun ; 15(1): 7419, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198388

RESUMO

Sequential lytic cycles driven by cascading transcriptional waves underlie pathogenesis in the apicomplexan parasite Toxoplasma gondii. This parasite's unique division by internal budding, short cell cycle, and jumbled up classically defined cell cycle stages have restrained in-depth transcriptional program analysis. Here, unbiased transcriptome and chromatin accessibility maps throughout the lytic cell cycle are established at the single-cell level. Correlated pseudo-timeline assemblies of expression and chromatin profiles maps transcriptional versus chromatin level transition points promoting the cell division cycle. Sequential clustering analysis identifies functionally related gene groups promoting cell cycle progression. Promoter DNA motif mapping reveals patterns of combinatorial regulation. Pseudo-time trajectory analysis reveals transcriptional bursts at different cell cycle points. The dominant burst in G1 is driven largely by transcription factor AP2XII-8, which engages a conserved DNA motif, and promotes the expression of 44 ribosomal proteins encoding regulon. Overall, the study provides integrated, multi-level insights into apicomplexan transcriptional regulation.


Assuntos
Cromatina , Proteínas de Protozoários , Regulon , Ribossomos , Análise de Célula Única , Toxoplasma , Toxoplasma/genética , Toxoplasma/metabolismo , Cromatina/metabolismo , Cromatina/genética , Regulon/genética , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/genética , Ribossomos/metabolismo , Ribossomos/genética , Regulação da Expressão Gênica , Regiões Promotoras Genéticas/genética , Ciclo Celular/genética , Humanos , Motivos de Nucleotídeos/genética , Transcriptoma , Proteínas Ribossômicas/metabolismo , Proteínas Ribossômicas/genética
8.
Hum Genomics ; 18(1): 74, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956740

RESUMO

BACKGROUND: Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. METHODS: We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. RESULTS: Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. CONCLUSION: The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.


Assuntos
Biomarcadores Tumorais , Glioma , Microambiente Tumoral , Humanos , Glioma/genética , Glioma/imunologia , Glioma/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Prognóstico , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Nomogramas , Feminino , Masculino , Perfilação da Expressão Gênica , Pessoa de Meia-Idade
9.
Hum Brain Mapp ; 45(11): e26784, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39031955

RESUMO

Early brain development is characterized by the formation of a highly organized structural connectome, which underlies brain's cognitive abilities and influences its response to diseases and environmental factors. Hence, quantitative assessment of structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the connectome from diffusion MRI data involves complex computations. For the perinatal period, these computations are further challenged by the rapid brain development, inherently low signal quality, imaging difficulties, and high inter-subject variability. These factors make it difficult to chart the normal development of the structural connectome. As a result, there is a lack of reliable normative baselines of structural connectivity metrics at this critical stage in brain development. In this study, we developed a computational method based on spatio-temporal averaging in the image space for determining such baselines. We used this method to analyze the structural connectivity between 33 and 44 postmenstrual weeks using data from 166 subjects. Our results unveiled clear and strong trends in the development of structural connectivity in the perinatal stage. We observed increases in measures of network integration and segregation, and widespread strengthening of the connections within and across brain lobes and hemispheres. We also observed asymmetry patterns that were consistent between different connection weighting approaches. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. Our proposed method also showed considerable agreement with an alternative technique based on connectome averaging. The new computational method and results of this study can be useful for assessing normal and abnormal development of the structural connectome early in life.


Assuntos
Encéfalo , Conectoma , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Feminino , Conectoma/métodos , Masculino , Adulto , Imagem de Tensor de Difusão/métodos , Vias Neurais/diagnóstico por imagem , Vias Neurais/crescimento & desenvolvimento , Imagem de Difusão por Ressonância Magnética/métodos , Processamento de Imagem Assistida por Computador/métodos , Adulto Jovem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/crescimento & desenvolvimento
10.
Mikrochim Acta ; 191(8): 485, 2024 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060720

RESUMO

Rare earth (RE)-doped CaS phosphors have been widely used as light-emitting components in various fields. Nevertheless, the application of nanosized CaS particles is still significantly limited by their poor water resistance and weak luminescence. Herein, a lattice-matching strategy is developed by growing an inert shell of cubic NaYF4 phase on the CaS luminescent core. Due to their similarity in crystal structure, a uniform core-shell heterostructure (CaS:Ce3+@NaYF4) can be obtained, which effectively protects the CaS:Ce3+ core from degradation in aqueous environment and enhances its luminescence intensity. As a proof of concept, a label-free aptasensor is further constructed by combining core-shell CaS:Ce3+@NaYF4 and Au nanoparticles (AuNPs) for the ultrasensitive detection of kanamycin antibiotics. Based on the efficient FRET process, the detection linear range of kanamycin spans from 100 to 1000 nM with a detection limit of 7.8 nM. Besides, the aptasensor shows excellent selectivity towards kanamycin antibiotics, and has been successfully applied to the detection of kanamycin spiked in tap water and milk samples, demonstrating its high potential for sensing applications.


Assuntos
Antibacterianos , Fluoretos , Ouro , Canamicina , Limite de Detecção , Nanopartículas Metálicas , Leite , Ítrio , Fluoretos/química , Antibacterianos/análise , Antibacterianos/química , Leite/química , Ítrio/química , Ouro/química , Nanopartículas Metálicas/química , Canamicina/análise , Canamicina/química , Aptâmeros de Nucleotídeos/química , Animais , Poluentes Químicos da Água/análise , Luminescência , Água Potável/análise , Técnicas Biossensoriais/métodos , Água/química , Transferência Ressonante de Energia de Fluorescência/métodos
11.
Microorganisms ; 12(6)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38930593

RESUMO

Ochrobactrum anthropi (O. anthropi) is found in water, soil, plants and animals. Even though it has low virulence, it has increasingly been found to cause a number of infectious diseases in people with low immunity. The identification of O. anthropi mainly uses biochemical methods, such as the API 20NE or Vitek-2. The typing studies of O. anthropi have mainly utilized PFGE, rep-PCR, AFLP, 16s rDNA sequencing, RecA-PCR RFLP, and MALDI-TOF MS. This study aims to evaluate the polymorphisms of variable-number tandem-repeats (VNTRs) within genomic DNA of O. anthropi strains. The tandem repeats (TRs) in genomic DNA are discovered using Tandem Repeat Finder software (version 4.09). Twelve different VNTRs are designated and assigned to the nomenclature. The primers for PCR of 12 loci are designed. The PCR product size is converted to the number of tandem repeats in every locus. The relatedness of 65 O. anthropi strains from geographically different countries are analyzed by means of 12-variable-number tandem-repeat analysis(MLVA-12). A total of 51 different genotypes are found in 65 O. anthropi strains. These strains, which were collected from the same environmental samples, hospitals, and countries, are clustered within the same or closely genotypes. The MLVA-12 assay has a good discriminatory power for species determination, typing of O. anthropi, and inferring the origin of bacteria.

12.
Int J Pharm ; 660: 124310, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38848796

RESUMO

Breast cancer has now replaced lung cancer as the most prevalent malignant tumor worldwide, posing a serious health risk to women. We have recently designed a promising option strategy for the treatment of breast cancer. In this work, cyclodextrin metal-organic frameworks with high drug-carrying properties were endo-crosslinked by 3,3'dithiodipropionyl chloride to form cubic phase gel nanoparticles, which were drug-loaded and then coated by MCF-7 cell membranes. After intravenous injection, this multifunctional nanomedicine achieved dramatically homologous targeting co-delivery of honokiol and indocyanine green to the breast tumor. Further, the disulfide bonds in the nanostructures achieved glutathione-responsive drug release, induced tumor cells to produce reactive oxygen species and promoted apoptosis, resulting in tumor necrosis, and at the same time, inhibited Ki67 protein expression, which enhanced photochemotherapy, and resulted in a 94.08 % in vivo tumor suppression rate in transplanted tumor-bearing mice. Thereby, this nanomimetic co-delivery system may have a place in breast cancer therapy due to its simple fabrication process, excellent biocompatibility, efficient targeted delivery of insoluble drugs, and enhanced photochemotherapy.


Assuntos
Compostos de Bifenilo , Neoplasias da Mama , Liberação Controlada de Fármacos , Glutationa , Verde de Indocianina , Lignanas , Estruturas Metalorgânicas , Fotoquimioterapia , Verde de Indocianina/administração & dosagem , Verde de Indocianina/química , Animais , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Células MCF-7 , Fotoquimioterapia/métodos , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/química , Estruturas Metalorgânicas/química , Glutationa/metabolismo , Lignanas/administração & dosagem , Lignanas/química , Lignanas/farmacologia , Camundongos Endogâmicos BALB C , Ciclodextrinas/química , Camundongos , Apoptose/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Espécies Reativas de Oxigênio/metabolismo , Camundongos Nus , Portadores de Fármacos/química , Compostos Alílicos , Fenóis
13.
Neuroimage ; 297: 120669, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38852805

RESUMO

The relationship between brain entropy (BEN) and early brain development has been established through animal studies. However, it remains unclear whether the BEN can be used to identify age-dependent functional changes in human neonatal brains and the genetic underpinning of the new neuroimaging marker remains to be elucidated. In this study, we analyzed resting-state fMRI data from the Developing Human Connectome Project, including 280 infants who were scanned at 37.5-43.5 weeks postmenstrual age. The BEN maps were calculated for each subject, and a voxel-wise analysis was conducted using a general linear model to examine the effects of age, sex, and preterm birth on BEN. Additionally, we evaluated the correlation between regional BEN and gene expression levels. Our results demonstrated that the BEN in the sensorimotor-auditory and association cortices, along the 'S-A' axis, was significantly positively correlated with postnatal age (PNA), and negatively correlated with gestational age (GA), respectively. Meanwhile, the BEN in the right rolandic operculum correlated significantly with both GA and PNA. Preterm-born infants exhibited increased BEN values in widespread cortical areas, particularly in the visual-motor cortex, when compared to term-born infants. Moreover, we identified five BEN-related genes (DNAJC12, FIG4, STX12, CETN2, and IRF2BP2), which were involved in protein folding, synaptic vesicle transportation and cell division. These findings suggest that the fMRI-based BEN can serve as an indicator of age-dependent brain functional development in human neonates, which may be influenced by specific genes.


Assuntos
Encéfalo , Conectoma , Entropia , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Recém-Nascido , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Conectoma/métodos , Lactente , Recém-Nascido Prematuro/fisiologia
14.
Int J Nanomedicine ; 19: 3737-3751, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699684

RESUMO

Background: Chemo-photodynamic combination therapy has demonstrated significant potential in the treatment of cancer. Triptolide (TPL), a naturally derived anticancer agent, when combined with the photosensitizer Chlorin e6 (Ce6), has shown to provide enhanced anti-tumor benefits. However, the development of stimuli-responsive nanovehicles for the co-delivery of TPL and Ce6 could further enhance the efficacy of this combination therapy. Methods: In this study, we synthesized a pH/ROS dual-responsive mPEG-TK-PBAE copolymer, which contains a pH-sensitive PBAE moiety and a ROS-sensitive thioketal (TK) linkage. Through a self-assembly process, TPL and Ce6 were successfully co-loaded into mPEG-TK-PBAE nanoparticles, hereafter referred to as TPL/Ce6 NPs. We evaluated the pH- and ROS-sensitive drug release and particle size changes. Furthermore, we investigated both the in vitro suppression of cellular proliferation and induction of apoptosis in HepG2 cells, as well as the in vivo anti-tumor efficacy of TPL/Ce6 NPs in H22 xenograft nude mice. Results: The mPEG-TK-PBAE copolymer was synthesized through a one-pot Michael-addition reaction and successfully co-encapsulated both TPL and Ce6 by self-assembly. Upon exposure to acid pH values and high ROS levels, the payloads in TPL/Ce6 NPs were rapidly released. Notably, the abundant ROS generated by the released Ce6 under laser irradiation further accelerated the degradation of the nanosystem, thereby amplifying the tumor microenvironment-responsive drug release and enhancing anticancer efficacy. Consequently, TPL/Ce6 NPs significantly increased PDT-induced oxidative stress and augmented TPL-induced apoptosis in HepG2 cells, leading to synergistic anticancer effects in vitro. Moreover, administering TPL/Ce6 NPs (containing 0.3 mg/kg of TPL and 4 mg/kg of Ce6) seven times, accompanied by 650 nm laser irradiation, efficiently inhibited tumor growth in H22 tumor-bearing mice, while exhibiting lower systemic toxicity. Conclusion: Overall, we have developed a tumor microenvironment-responsive nanosystem for the co-delivery of TPL and Ce6, demonstrating amplified synergistic effects of chemo-photodynamic therapy (chemo-PDT) for hepatocellular carcinoma (HCC) treatment.


Assuntos
Apoptose , Clorofilídeos , Diterpenos , Neoplasias Hepáticas , Camundongos Nus , Fenantrenos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Espécies Reativas de Oxigênio , Animais , Humanos , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Células Hep G2 , Neoplasias Hepáticas/tratamento farmacológico , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/administração & dosagem , Porfirinas/farmacocinética , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/farmacocinética , Diterpenos/administração & dosagem , Concentração de Íons de Hidrogênio , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Apoptose/efeitos dos fármacos , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Compostos de Epóxi/administração & dosagem , Nanopartículas/química , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Liberação Controlada de Fármacos , Proliferação de Células/efeitos dos fármacos , Polietilenoglicóis/química , Terapia Combinada
15.
Phys Rev Lett ; 132(11): 116201, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38563913

RESUMO

Intriguing topological polar structures in oxide nanofilms have drawn growing attention owing to their immense potential applications in nanoscale electronic devices. Here, we report a novel route to mechanically manipulate polar structures via flexoelectricity in wrinkled thin films. Our results present a flexoelectric polar transition from a nonpolar state to uniaxial polar stripes, biaxial meronlike or antimeronlike polar structures, and polar labyrinths by varying wrinkle morphologies. The evolution mechanisms and the outstanding mechanical tunability of these flexoelectric polar patterns were investigated theoretically and numerically. This strategy based on flexoelectricity for generating nontrivial polar structures will no longer rely on the superlattice structure and can be widely applicable to all centrosymmetric or noncentrosymmetric materials, providing a broader range of material and structure candidates for polar topologies.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38656402

RESUMO

The combination of shikonin (SKN) and gefitinib (GFB) can reverse the drug resistance of lung cancer cells by affecting energy metabolism. However, the poor solubility of SKN and GFB limits their clinical application because of low bioavailability. Wheat germ agglutinin (WGA) can selectively bind to sialic acid and N-acetylglucosamine on the surfaces of microfold cells and enterocytes, and is a targeted biocompatible material. Therefore, we created a co-delivery micelle system called SKN/GFB@WGA-micelles with the intestinal targeting functions to enhance the oral absorption of SKN and GFB by promoting mucus penetration for nanoparticles via oral administration. In this study, Caco-2/HT29-MTX-E12 co-cultured cells were used to simulate a mucus/enterocyte dual-barrier environment, and HCC827/GR cells were used as a model of drug-resistant lung cancer. We aimed to evaluate the oral bioavailability and anti-tumor effect of SKN and GFB using the SKN/GFB@WGA-micelles system. In vitro and in vivo experimental results showed that WGA promoted the mucus penetration ability of micelles, significantly enhanced the uptake efficiency of enterocytes, improved the oral bioavailability of SKN and GFB, and exhibited good anti-tumor effects by reversing drug resistance. The SKN/GFB@WGA-micelles were stable in the gastrointestinal tract and provided a novel safe and effective drug delivery strategy.

17.
Heliyon ; 10(6): e27953, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545178

RESUMO

Background and objectives: The neutrophil-to-lymphocyte ratio (NLR) is a widely recognized marker of inflammation in peripheral blood. However, its specific role in neuronal intranuclear inclusion disease (NIID) has not been reported. This study aims to investigate the relationship between NIID and NLR. Methods: A multicenter database was collected, including 157 NIID patients from seven hospitals (The Affiliated Hospital of Xuzhou Medical University, Yantai Yuhuangding Hospital, Tengzhou Central People's Hospital,The Affiliated Brain Hospital of Nanjing Medical University, Liaocheng People's Hospital,The Second Hospital of Shandong University, Inner Mongolia People's Hospital, Xuanwu Hospital Capital Medical University,The First Affiliated Hospital of USTC), along with 157 age- and gender-matched healthy control subjects. White blood cell counts (including neutrophils, lymphocytes, monocytes, eosinophils, and basophils) were obtained, and the NLR was calculated. Additionally, cognitive impairment was assessed using clinical evaluation scores. Results: NIID patients exhibited significantly higher NLR values compared to the healthy control group (p < 0.001). The plasma NLR levels in NIID patients showed a weak positive correlation with disease duration (r = 0.219, p = 0.016). However, no significant correlations were found between NLR and age of onset or cognitive impairment (p > 0.05). Conclusion: There is a significant association between NLR and NIID, suggesting a potential role of peripheral blood inflammation in the pathogenesis of NIID.

18.
Ying Yong Sheng Tai Xue Bao ; 35(2): 480-488, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523106

RESUMO

The construction of urban ecological green wedges, which can mitigate the heat island effect through cooling and ventilation effects, is an important way to enhance the adaptation of cities to climate change. Dynamic monitoring and periodic assessment of both the conservation status and cooling effect of ecological green wedges is a key to ensure the heat mitigation benefits. Based on multi-source remote sensing data, we systematically analyzed the land use changes of six ecological green wedges in Wuhan in 2013 and 2020 using the methods of Markov transfer matrix, land use dynamics, and comprehensive index of land use degree, and evaluated the changes in surface temperature of the ecological green wedges and their cooling island effect. Results showed that the ecological green wedges in Wuhan generally had a large amount of construction land encroaching on ecological land from 2013 to 2020, with the water decreased the most. With the continuous deterioration of ecological green wedges, their land surface temperatures showed rising trends, together with significant weakening trends in cooling island effects. Among all the six wedges, the Dadonghu, Tangxun, and Wuhu exhibited relatively better ecological conservation, slighter land use change and lower overall development degree. Qinglinghu and Houguanhu demonstrated average levels of conservation. Fuhe experienced the most severe change under the significant influence of the westward policy of Wuhan City, with the proportion of water decreasing by 7.1%, warming up by 3.00 ℃, and the largest reduction in cooling distance for the cooling island effect, amounting to about 210 m. The results provided scientific evidence for the urban heat island mitigation-oriented planning and management of ecological green wedges for Wuhan City.


Assuntos
Temperatura Alta , Água , Cidades , Temperatura , China , Monitoramento Ambiental/métodos
19.
Int J Biol Macromol ; 264(Pt 2): 130692, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460646

RESUMO

In this study, a multi-functional packaging film was fabricated, utilizing the natural polysaccharide chitosan (CS) as the base material, integrating natural blueberry anthocyanin (AN) as pH-responsive indicator, and reinforced with cellulose nanocrystals (CNCs). The implications of addition levels of CNCs on the characteristics of the films were systematically investigated, resulting in that CS-AN-CNCs 9 % film exhibited optimal performance. Specifically, the film showed a substantial enhancement in maximum tensile strength from 15 MPa to 35 MPa; On the other hand, the swelling degree properties, the oxygen permeability and water vapor permeability decreased from 159.2 % to 92.0 %, from 51.7 g/(m2d) to 12.2 g/(m2d), from 31.6 × 10-12 g/(m·s·Pa) to 1.6 × 10-12 g/(m·s·Pa), respectively. Moreover, the CS-AN-CNCs 9 % film exhibited antioxidant, antibacterial, coupled with a color metrically responsive to pH variations, displaying great potential in indicating the shrimp freshness and delaying spoilage. Another notable advantage of the-prepared packaging material lies in its completely biodegradability, therefore meeting the requirement of environmental protection. Therefore, the prepared CS-AN-CNCs film as an intelligent packaging solution with potential applications in food preservation and freshness monitoring applications.


Assuntos
Quitosana , Nanopartículas , Animais , Antocianinas , Celulose , Embalagem de Medicamentos , Crustáceos , Embalagem de Alimentos , Concentração de Íons de Hidrogênio
20.
Acta Pharm Sin B ; 14(3): 1111-1131, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38486983

RESUMO

Conventional photodynamic therapy (PDT) approaches face challenges including limited light penetration, low uptake of photosensitizers by tumors, and lack of oxygen in tumor microenvironments. One promising solution is to internally generate light, photosensitizers, and oxygen. This can be accomplished through endogenous production, such as using bioluminescence as an endogenous light source, synthesizing genetically encodable photosensitizers in situ, and modifying cells genetically to express catalase enzymes. Furthermore, these strategies have been reinforced by the recent rapid advancements in synthetic biology. In this review, we summarize and discuss the approaches to overcome PDT obstacles by means of endogenous production of excitation light, photosensitizers, and oxygen. We envision that as synthetic biology advances, genetically engineered cells could act as precise and targeted "living factories" to produce PDT components, leading to enhanced performance of PDT.

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