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1.
Opt Express ; 32(6): 10429-10443, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571255

RESUMO

With the deepening of research and the further differentiation of damage types, and to compensate for both linear and nonlinear damage in visible light communication systems (VLCs), we propose a novel discrete wavelet transform-assisted convolutional neural network (DWTCNN) equalizer that combines the advantages of wavelet transform and deep learning methods. More specifically, wavelet transform is used in DWTCNN to decompose the signal into diverse coefficient series and employ an adaptive soft-threshold method to eliminate redundant information in the signal. The coefficients are then reconstructed to achieve complete signal compensation. The experimental results show that the proposed DWTCNN equalizer can significantly reduce nonlinear impairment and improve system performance with the bit error rate (BER) under the 7% hard-decision forward error correction (HD-FEC) limit of 3.8 × 10-3. We also experimentally compared DWTCNN with the Long Short-Term Memory (LSTM) and entity extraction neural network (EXNN) equalizer, the Q factor has been improved by 0.76 and 0.53 dB, and the operating ranges of the direct current (DC) bias have increased by 4.76% and 23.5%, respectively.

2.
BMC Musculoskelet Disord ; 25(1): 726, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256670

RESUMO

PURPOSE: The objective of this systematic review and metaanalysis is to compare the efficacy and safety of decompression alone versus decompression plus fusion in single-level lumbar spinal stenosis with spondylolisthesis. METHODS: A comprehensive search of the PubMed, Embase, Cochrane Library, and Ovid Medline databases was conducted to find randomized control trials (RCTs) or cohort studies that compared decompression alone and decompression plus fusion in single-level lumbar spinal stenosis with spondylolisthesis. Operation time; reoperation; postoperative complications; postoperative Oswestry disability index(ODI) scores and scores related to back and leg pain were collected from eligible studies for meta-analysis. RESULTS: We included 3 randomized controlled trials and 9 cohort studies with 6182 patients. The decompression alone group showed less operative time(P < 0.001) and intraoperative blood loss(p = 0.000), and no significant difference in postoperative complications was observed in randomized controlled trials(p = 0.428) or cohort studies(p = 0.731). There was no significant difference between the other two groups in reoperation(P = 0.071), postoperative ODI scores and scores related to back and leg pain. CONCLUSIONS: In this study, we found that the decompression alone group performed better in terms of operation time and intraoperative blood loss, and there was no significant difference between the two surgical methods in rate of reoperation and postoperative complications, ODI, low back pain and leg pain. Therefore, we come to the conclusion that decompression alone is not inferior to decompression and fusion in patients with single-level lumbar spinal stenosis with spondylolisthesis.


Assuntos
Descompressão Cirúrgica , Vértebras Lombares , Fusão Vertebral , Estenose Espinal , Espondilolistese , Humanos , Descompressão Cirúrgica/métodos , Descompressão Cirúrgica/efeitos adversos , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação/estatística & dados numéricos , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Estenose Espinal/diagnóstico , Estenose Espinal/etiologia , Estenose Espinal/cirurgia , Espondilolistese/complicações , Espondilolistese/diagnóstico , Espondilolistese/cirurgia , Resultado do Tratamento
3.
Horm Metab Res ; 55(8): 573-579, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36990459

RESUMO

MicroRNAs (miRNAs) have been discovered to play critical role in regulating prostate cancer (PC) progression. The function role of miR-629 in tumor progression of PC has not been studied. Here, we found that miR-629 was markedly upregulated in PC as determined using the cancer genome atlas (TCGA) dataset, clinical tissues, and cell lines. Functional analysis (MTT assays, colony formation assays, soft agar growth assay and BrdU incorporation assay) indicated that overexpression of miR-629 was drastically promoted, while miR-629-in significantly suppressed cell proliferation. LATS2 was predicted as a direct target of miR-629 and was confirmed by western blot and dual luciferase assay. Through downregulation of large tumor suppressor 2 (LATS2) by overexpression of miR-629, the p21 mRNA and protein were decreased while the Cyclin D3 mRNA and protein were enhanced, suggesting promoting of cell proliferation process. Additionally, knockdown of LATS2 reversed the inhibitory effect by miR-629-in in PC. Our study indicated that miR-629 might serve as a new promising target for PC treatment.


Assuntos
MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
4.
Pharm Biol ; 61(1): 416-426, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36786302

RESUMO

CONTEXT: Morroniside (MOR) possesses antiosteoporosis (OP) effects, but its molecular target and relevant mechanisms remain unknown. OBJECTIVE: We investigated the effects of MOR on glucocorticoid-induced OP and osteoblastogenesis and its underlying mechanisms. MATERIALS AND METHODS: The effects of MOR (10-100 µM) on the proliferation and differentiation of MC3T3-E1 cells were studied in vitro. The glucocorticoid-induced zebrafish OP model was treated with 10, 20 and 40 µM MOR for five days to evaluate its effects on vertebral bone density and related osteogenic markers. In addition, molecular targets prediction and molecular docking analysis were carried out to explore the binding interactions of MOR with the target proteins. RESULTS: In cultured MC3T3-E1 cells, 20 µM MOR significantly increased cell viability (1.64 ± 0.12 vs. 0.95 ± 0.16; p < 0.01) and cell differentiation (1.57 ± 0.01 vs. 1.00 ± 0.04; p < 0.01) compared to the control group. MOR treatment significantly ameliorated vertebral bone loss in the glucocorticoid-induced OP zebrafish model (0.86 ± 0.02 vs. 0.40 ± 0.03; p < 0.01) and restored the expression of osteoblast-specific markers, including ALP, Runx2 and Col-І. Ligand-based target prediction and molecular docking revealed the binding interaction between MOR and the glucose pockets in sodium-glucose cotransporter 2 (SGLT2). DISCUSSION AND CONCLUSIONS: These findings demonstrated that MOR treatment promoted osteoblastogenesis and ameliorated glucocorticoid-induced OP by targeting SGLT2, which may provide therapeutic potential in managing glucocorticoid-induced OP.


Assuntos
Glucocorticoides , Osteoporose , Animais , Glucocorticoides/toxicidade , Peixe-Zebra , Linhagem Celular , Simulação de Acoplamento Molecular , Transportador 2 de Glucose-Sódio/efeitos adversos , Transportador 2 de Glucose-Sódio/metabolismo , Diferenciação Celular , Osteogênese , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Sódio/efeitos adversos , Sódio/metabolismo , Osteoblastos
5.
Opt Express ; 30(15): 26701-26715, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236857

RESUMO

Herein, we propose a novel entity extraction neural network (EXNN) with a newly designed sampling convolution kernel approach and a deep learning-based structure to differentiate noise in visible light communication (VLC) systems. In particular, EXNN is used to extract linear and nonlinear distortion in a received signal as an entity and compensate for the signal by removing it. First, we designed a deep learning structure tailored for VLC systems, used experimentation to validate our algorithm's usability, and determined an appropriate range for the hyper-parameters that govern the PAM-8 system. Second, we compared our approach with existing finite impulse response (FIR) linear and Volterra nonlinear compensation algorithms via experiments. Below the hard-decision forward error correction (HD-FEC) threshold limit of 3.8×10-3, experimental results show that the use of the EXNN increased the operating range of the direct current (DC) bias and the voltage by ∼33.3% and by ∼50% under optimal conditions, respectively. Furthermore, under corresponding optimal power conditions, the proposed approach improved the Q factor of the VLC system by 0.36 and 1.57 dB compared with the aforementioned linear and nonlinear equalizers, respectively. To the best of our knowledge, this is the first time that a deep learning operator has been custom-designed for the VLC system and we have named the completely redesigned network with this sampling convolution kernel operator as EXNN.

6.
Biochem Biophys Res Commun ; 525(2): 498-504, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32111353

RESUMO

BACKGROUND: Many studies had identified that MicroRNAs (miRNAs) could affect bone metabolism by regulating the expression of various proteins. This study explored the effect and mechanism of miR-532-3p on osteogenic differentiation. METHODS: We analyzed the content of miR-532-3p in osteoporosis patients, osteoporosis rats, and osteogenic induced MC3T3-E1 cells. MiR-532-3p mimic or inhibitor utilized to alter intracellular miR-532-3p content. MTT method executed to detect the effect of miR-532-3p on osteoblast proliferation. Real-time qPCR, Western blot, alkaline phosphatase staining, and alizarin red staining utilized to ascertain the influence of miR-532-3p on osteogenic differentiation. Then, databases and a dual-luciferase reporter gene assay used to verify the target of miR-532-3p. Furthermore, the lentiviral vector was utilized to overexpress interesting target gene expression and checked whether the target gene was involved in the regulation of osteogenic differentiation by miR-532-3p. RESULTS: MiR-532-3p expression boosted in low bone mineral density (BMD) patients and rats. In MC3T3-E1 cells, miR-532-3p expression gradually decreased as osteogenic induction matures. MiR-532-3p mimic negatively regulated succinate dehydrogenase (SDH) activity, alkaline phosphatase (ALP) activity, mineralization ability, the osteogenic-associated gene (Col1A1, Runx2, ALP, OPN, and OCN) and E-26 transformation specific-1 (ETS1) expression of MC3T3-E1 cells. Things are the opposite of the miR-532-3p inhibitor. ETS1 identified as the miR-532-3p target gene, and miR-532-3p could inhibit its expression. Besides, improved ETS1 expression could rescue the suppressive effect of miR-532-3p mimic on osteogenic differentiation. CONCLUSION: miR-532-3p can suppress osteogenic differentiation by downregulating ETS1 expression.


Assuntos
Osteoblastos/citologia , Proteína Proto-Oncogênica c-ets-1/genética , Animais , Densidade Óssea , Diferenciação Celular , Linhagem Celular , Regulação para Baixo , Feminino , Humanos , Camundongos , Osteoblastos/metabolismo , Osteogênese , Ratos Sprague-Dawley , Regulação para Cima
7.
Bioorg Med Chem ; 27(20): 114938, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31488358

RESUMO

4-Anilinoquinazoline derivatives function as tyrosine kinase inhibitors (TKIs). Novel TKIs are needed for cancer mutations and drug-resistant cells. We designed and synthesized 4-anilinoquinazoline derivatives with substitutions at quinazoline positions 6, 7 and 4 using a binding model with multi-target receptor tyrosine kinases, and assessed their antitumor activity against five human tumor cell lines (HepG2, A549, MCF-7, DU145, SH-SY5Y). The majority of the compounds inhibited the proliferation of all the cancer cell types, with some compounds displaying selective inhibition. Compounds 21, 25, 27, and 37 displayed IC50 values of 7.588, 8.619, 6.936, and 8.516 µM, respectively, for A549 cells, which were much lower than that of Gefitinib (14.803 µM). Compound 32 displayed an IC50 value of 2.756 µM for DU145 cells. The representative compound 40 had unexceptionable broad-spectrum inhibition for all cancer cell types, and demonstrate inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFR-ß), and epidermal growth factor receptor (EGFR) with IC50 values of 46.4, 673.6 and 384.8 nM, respectively, which were similar to those of Sorafenib for VEGFR-2 and PDGFR-ß (140.6 and 582.7 nM, respectively). Molecular docking results supported the molecular level assay results. Data for production of reactive oxygen species and assessment of matrix metalloproteinase corroborated the strong anti-proliferative effect of compound 40. The compound also displayed robust antitumor efficacy and relativity lower toxicity in a xenograft model. These attributes were similar to those of Sorafenib. Compound 40 drug warrants further study as a candidate.


Assuntos
Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Compostos de Anilina/síntese química , Compostos de Anilina/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Espécies Reativas de Oxigênio/análise , Receptores Proteína Tirosina Quinases/metabolismo , Relação Estrutura-Atividade
8.
Biochem Biophys Res Commun ; 502(3): 299-306, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29772237

RESUMO

Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) are critically involved in tumor progression. In current study, we reported a novel lncRNA signature correlated with bladder cancer development. Particularly, the lncRNA long stress-induced noncoding transcript 5 (LSINCT5) is significantly upregulated in human bladder cancer cell lines and tumor specimens. Meanwhile, high LSINCT5 expression correlates with poor prognosis, enhances tumor sphere formation and invasion in vitro. In vivo xenograft tumor growth is also elevated by LSINCT5 overexpression. Mechanistic investigations showed that LSINCT5 could physically interact with NCYM, a de novo gene product from the MYCN cis-antisense RNA and inhibit GSK3ß activity leading to enhanced Wnt/ß-catenin signaling activation and epithelial mesenchymal transition (EMT). Taken together, our findings have created a novel LSINCT5 mediated process which facilitates bladder cancer progression and may provide a potential target for therapeutic intervention.


Assuntos
Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Animais , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Técnicas de Silenciamento de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Longo não Codificante/antagonistas & inibidores , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Regulação para Cima , Neoplasias da Bexiga Urinária/patologia , Via de Sinalização Wnt , beta Catenina/metabolismo
9.
J Labelled Comp Radiopharm ; 61(2): 42-53, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28833405

RESUMO

Four novel 18 F-labeled quinazoline derivatives with low lipophilicity, [18 F]4-(2-fluoroethoxy)-6,7-dimethoxyquinazoline ([18 F]I), [18 F]4-(3-((4-(2-fluoroethoxy)-7-methoxyquinazolin-6-yl)oxy)propyl)morpholine ([18 F]II), [18 F]4-(2-fluoroethoxy)-7-methoxy-6-(2-methoxyethoxy)quinazoline ([18 F]III), and [18 F]4-(2-fluoroethoxy)-6,7-bis(2-methoxyethoxy)quinazoline ([18 F]IV), were synthesized via a 2-step radiosynthesis procedure with an overall radiochemical yield of 10% to 38% (without decay correction) and radiochemical purities of >98%. The lipophilicity and stability of labeled compounds were tested in vitro. The log P values of the 4 radiotracers ranged from 0.52 to 1.07. We then performed ELISA to measure their affinities to EGFR-TK; ELISA assay results indicated that each inhibitor was specifically bounded to EGFR-TK in a dose-dependent manner. The EGFR-TK autophosphorylation IC50 values of [18 F]I, [18 F]II, [18 F]III, and [18 F]IV were 7.732, 0.4698, 0.1174, and 0.1176 µM, respectively. All labeled compounds were evaluated via cellular uptake and blocking studies in HepG2 cell lines in vitro. Cellular uptake and blocking experiment results indicated that [18 F]I and [18 F]III had excellent cellular uptake at 120-minute postinjection in HepG2 carcinoma cells (51.80 ± 3.42%ID/mg protein and 27.31 ± 1.94%ID/mg protein, respectively). Additionally, biodistribution experiments in S180 tumor-bearing mice in vivo indicated that [18 F]I had a very fast clearance in blood and a relatively high uptake ratio of tumor to blood (4.76) and tumor to muscle (1.82) at 60-minute postinjection. [18 F]III had a quick clearance in plasma, and its highest uptake ratio of tumor to muscle was 2.55 at 15-minute postinjection. These experimental results and experiences were valuable for the further exploration of novel radiotracers of quinazoline derivatives.


Assuntos
Radioisótopos de Flúor/química , Neoplasias Experimentais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Quinazolinas/química , Compostos Radiofarmacêuticos/síntese química , Animais , Bovinos , Feminino , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos ICR , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
10.
J Cell Biochem ; 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28980707

RESUMO

BACKGROUND: Epigenetic factors of microRNAs (miRNAs) are important biomarkers and modulators in human prostate cancer (PCa). In this work, we characterized the expression, biomarker-potential and functional regulation of miR-588 in PCa. METHODS: Endogenous miR-588 levels were quantified by qRT-PCR in both prostate-specific antigen (PSA)-negative and PSA-positive PCa cell lines, as well as human PCa tumors. The associations between endogenous miR-588 and PCa patients' clinical outcomes and postoperative overall survival were statistically examined. Moreover, in both PSA-negative DU145 and PSA-positive LNCaP, downregulation of miR-588 was achived by transduction of miR-588 inhibitor lentivirus. The subsequent effects of miR-588 downregulation on PCa cell developments were investigated both in vitro and in vivo. RESULTS: MiR-588 was profoundly upregulated in both PSA-negative and PSA-positive PCa cells, as well as in PCa tumors. Significant miR-588 upregulation was found to be closely associated with PCa patients' poor clinical outcomes and shorter postoperative overall survivals. In DU145 and LNCaP cell lines, lentiviral transduction markedly downregulated endogenous miR-588 levels. MiR-588 downregulation was shown to profoundly inhibit PCa proliferation in vitro and xenograft in vivo. CONCLUSION: Aberrant upregulation of endogenous miR-588 in PCa patients may be a prognostic biomarker, indicative of their poor clinical outcomes. Inhibiting endogenous miR-588 may also serve as a therapeutic target for PCa treatment. This article is protected by copyright. All rights reserved.

11.
ACS Nano ; 18(33): 22080-22094, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39102350

RESUMO

Meningeal vascular network is significant in neurology and neurosurgery. However, high-resolution imaging of intact meningeal vascular network is lacking. In this work, we develop a practical experimental method to ensure that the intact meninges are morphologically unfolded and fixed in an agarose gel. With the help of high-brightness polymer dots (Pdots) as probe, macroscopic and detailed imaging of the vascular network on the intact dorsal meninges can be performed. Meningeal vessels are symmetrically distributed along the superior sagittal sinus, and the distribution of meningeal vessels had a certain degree of hierarchy. The meninges are thicker blood vessels and capillary networks from the outside to the inside. Moreover, the diameter of the capillaries is 3.96 ± 0.89 µm. Interestingly, meningeal primo vessels in the central nervous system of mice is imaged with the diameter of 4.18 ± 1.18 µm, which has not been reported previously. It is worth mentioning that we found that orthotopic xenografts of brain tumors caused the appearance of corneal neovascularization and morphological changes in optic nerve microvessels. In conclusion, our work provides an effective Pdots-based imaging method for follow-up research on meningeal vascular-related diseases, and illustrates that the eye can serve as a window for the prevention and diagnosis of brain diseases.


Assuntos
Encéfalo , Meninges , Animais , Camundongos , Meninges/diagnóstico por imagem , Meninges/irrigação sanguínea , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Corantes Fluorescentes/química , Humanos , Olho/irrigação sanguínea , Olho/diagnóstico por imagem , Polímeros/química , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imagem Óptica , Pontos Quânticos/química
12.
J Chromatogr A ; 1714: 464560, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38070304

RESUMO

The Fourier deconvolution ion mobility spectrometer (FDIMS) offers multiplexing and improves the resolving power and signal-to-noise ratio. To evaluate the FDIMS as a detector for gas chromatography for the analysis of complex samples, we connected a drift tube ion mobility spectrometer to a commercial gas chromatograph and compared the performance including resolving power, sensitivity, and linear range using 2,6-di­tert-butylpyridine. Mixed standards were also injected into the tandem system to evaluate the performance under optimized conditions. A complex plant extract sample used as natural flavoring was investigated using the resulting system. The results show that the instrument implemented with the Fourier deconvolution multiplexing method demonstrated higher performance over the traditional signal averaging method including higher resolving power, better limit of detection, and wider linear range for a variety of compounds and natural plant extract flavorings.


Assuntos
Extratos Vegetais , Cromatografia Gasosa/métodos
13.
Aging Cell ; : e14327, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39207121

RESUMO

Research has shown that sustained protein restriction can improve the effects of a high-fat diet on health and extend lifespan. However, long-term adherence to a protein-restricted diet is challenging. Therefore, we used a fly model to investigate whether periodic protein restriction (PPR) could also mitigate the potential adverse effects of a high-fat diet and extend healthy lifespan. Our study results showed that PPR reduced body weight, lipid levels, and oxidative stress induced by a high-fat diet in flies and significantly extended the healthy lifespan of male flies. Lipid metabolism and transcriptome results revealed that the common differences between the PPR group and the control group and high-fat group showed a significant decrease in palmitic acid in the PPR group; the enriched common differential pathways Toll and Imd were significantly inhibited in the PPR group. Further analysis indicated a significant positive correlation between palmitic acid levels and gene expression in the Toll and Imd pathways. This suggests that PPR effectively improves fruit fly lipid metabolism, reduces palmitic acid levels, and thereby suppresses the Toll and Imd pathways to extend the healthy lifespan of flies. Our study provides a theoretical basis for the long-term effects of PPR on health and offers a new dietary adjustment option for maintaining health in the long term.

14.
Food Funct ; 15(15): 7920-7935, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-38979640

RESUMO

Early dietary patterns potentially influence the health status and lifespan throughout adulthood and the entire lifespan. However, dietary behaviors are difficult for everyone to control during adolescence. It is even more important to study the effects of interventions of early dietary patterns on the lifespan under arbitrary feeding conditions. The research involves observing the survival status and lifespan of rats from weaning to adulthood with three different dietary patterns (a high-carbohydrate diet (HC), a high-protein diet (HP), and a high-fat diet (HF)) under ad libitum feeding conditions. The administration of high-carbohydrate diets leads to a significant extension of both median and maximum survival times (P < 0.05) in Wistar rats. Furthermore, it markedly enhanced the spatial memory capacity, mitigated the occurrence of liver and kidney pathological outcomes in elderly rats, and increased the abundance of gut microbiota improving amino acid metabolism. Additionally, feeding rats a high-carbohydrate diet improved glutathione (GSH) synthesis and recycling and activated the expression and upregulation of the lifespan-related proteins Foxo3a/Sirt3 and the key metabolic enzyme GPX-4. The high-carbohydrate diet from weaning to adulthood may potentially extend the lifespan by enhancing rat systemic glutathione synthesis, recycling, and improving the redox state pathway.


Assuntos
Homeostase , Longevidade , Oxirredução , Ratos Wistar , Desmame , Animais , Ratos , Masculino , Microbioma Gastrointestinal , Carboidratos da Dieta/metabolismo , Fígado/metabolismo , Glutationa/metabolismo , Dieta Hiperlipídica , Multiômica
15.
Int J Pharm ; 661: 124457, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38992736

RESUMO

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.


Assuntos
Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Flavonoides , Células-Tronco Mesenquimais , Osteogênese , Osteoporose , Animais , Osteoporose/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Feminino , Osteogênese/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Flavonoides/administração & dosagem , Flavonoides/química , Flavonoides/farmacologia , Camundongos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Durapatita/química , Durapatita/administração & dosagem , Camundongos Endogâmicos C57BL , Liberação Controlada de Fármacos
16.
ACS Nano ; 18(20): 13117-13129, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38727027

RESUMO

The complexity, heterogeneity, and drug resistance of diseases necessitate a shift in therapeutic paradigms from monotherapy to combination therapy, which could augment treatment efficiency. Effective treatment of advanced osteoarthritis (OA) requires addressing three key factors contributing to its deterioration: chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation. Herein, we present a supramolecular nanomedicine of multifunctionality via molecular recognition and self-assembly. The employed macrocyclic carrier, zwitterion-modified cavitand (CV-2), not only accurately loads various drugs but also functions as a therapeutic agent with lubricating properties for the treatment of OA. Kartogenin (KGN), a drug for articular cartilage regeneration and protection, and flurbiprofen (FP), an anti-inflammatory agent, were coloaded onto CV-2 assembly, forming a supramolecular nanomedicine KGN&FP@CV-2. The three-in-one combination therapy of KGN&FP@CV-2 addresses the three pathological features for treating OA collectively, and thus provides long-term therapeutic benefits for OA through sustained drug release and intrinsic lubrication in vivo. The multifunctional integration of macrocyclic delivery and therapeutics provides a simple, flexible, and universal platform for the synergistic treatment of diseases involving multiple drugs.


Assuntos
Flurbiprofeno , Osteoartrite , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Animais , Flurbiprofeno/química , Flurbiprofeno/administração & dosagem , Flurbiprofeno/farmacologia , Ácidos Ftálicos/química , Ácidos Ftálicos/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Portadores de Fármacos/química , Lubrificação , Liberação Controlada de Fármacos , Camundongos , Masculino , Anilidas
17.
Front Chem ; 11: 1162183, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970401

RESUMO

Selective hydrogenation of nitrobenzene (SHN) is an important approach to synthesize aniline, an essential intermediate with extremely high research significance and value in the fields of textiles, pharmaceuticals and dyes. SHN reaction requires high temperature and high hydrogen pressure via the conventional thermal-driven catalytic process. On the contrary, photocatalysis provides an avenue to achieve high nitrobenzene conversion and high selectivity towards aniline at room temperature and low hydrogen pressure, which is in line with the sustainable development strategies. Designing efficient photocatalysts is a crucial step in SHN. Up to now, several photocatalysts have been explored for photocatalytic SHN, such as TiO2, CdS, Cu/graphene and Eosin Y. In this review, we divide the photocatalysts into three categories based on the characteristics of the light harvesting units, including semiconductors, plasmonic metal-based catalysts and dyes. The recent progress of the three categories of photocatalysts is summarized, the challenges and opportunities are pointed out and the future development prospects are described. It aims to give a clear picture to the catalysis community and stimulate more efforts in this research area.

18.
Front Surg ; 10: 1103804, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816008

RESUMO

Purpose: This study aimed to compare the surgical efficacy of enlarged laminectomy with lateral mass screw fixation (EL-LMSF) and anterior cervical decompression and fusion (ACDF) for multilevel cervical myelopathy and radiculopathy (CMR) related to kyphosis. Methods: 75 patients were retrospectively reviewed and divided into ACDF and EL-LMSF group. Clinical results including operative time, blood loss, and postoperative complications were compared. The JOA scoring system was used to evaluate spinal cord function and the VAS score evaluate nerve root pain severity. Cervical alignment a C2-C7 was measured with Cobb method and compared to confirm the reconstruction effect. Results: Data on 75 patients (M/F: 41:34; EL-LMSF/ACDF:42/33) with the mean age of 57.5 years (range 43-72 year old) were reviewed retrospectively. Discectomy and/or sub-toal corpectomy in ACDF group was performed with a mean of 3.24 levels (range, 3-4). Enlarged laminectomy in EL-LMSF group was performed with a mean of 3.89 enlarged levels (range, 3-5). The procedure of ACDF group showed a shorter operation time (103 ± 22 min vs. 125 ± 37 min, P = 0.000) and less blood loss (78 ± 15 ml vs. 226 ± 31 ml, P = 0.000) compared than that of the EL-LMSF group. Patients treated with EL-LMSF indicated lower VAS for upper extremity (1.3 ± 1.7 vs. 3.3 ± 1.3, P = 0.003) and better curvature corrected (10.7 ± 4.2° vs. 8.5 ± 3.5°, P = 0.013). The difference were of statistical significance. No statistical difference was found after surgery in the JOA score (14.1 ± 1.7 vs. 13.5 ± 2.1, P = 0.222). During the follow-up period, 15.2% of patients in the ACDF group had complications including 2 cases with transient dysphagia, 1 case with C5 palsy, 1 case with axial pain, and 1 case with screw pullout 3 month after surgery. However, only 9.5% of cases in the EL-LMSF group experienced complications, including 3 cases of axial pain and 1 case of epidural hematoma. Conclusion: The EL-LMSF procedure requires a longer operation time and more blood loss because of the incision of the stenosed foramen. However, the procedure has obvious advantages in relieving nerve root symptoms and correcting cervical curvature with fewer postoperative complications.

19.
Adv Healthc Mater ; 11(21): e2200978, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36027786

RESUMO

Ocular diseases are mainly caused by vascular aberrations in the eye, and accurate imaging and analysis of the ocular vascular structure is crucial. In this study, poly(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT) polymer dots (Pdots), with the advantages of easy synthesis, high brightness, and low toxicity, are used as nanoprobes to perform high-resolution imaging of the vasculature of the eyeball and optic nerve. Moreover, rapid imaging of the choroidal microvessels is carried out by stereoscopic fluorescence microscopy with a resolution of up to 1.6 µm. The comprehensive 3D vascular information of retinal aorta and optic nerve microvessels is obtained by combining tissue clearing and multiphoton microscopy. In addition, the vascular density of Schlemm's canal and iris blood vessels is compared between the conjunctivitis mice and the normal mice. These results suggest that PFBT Pdots have great application potential in the fast and accurate imaging of ocular diseases.


Assuntos
Conjuntivite , Pontos Quânticos , Animais , Camundongos , Pontos Quânticos/química , Polímeros/química , Microscopia de Fluorescência , Olho
20.
Front Nutr ; 9: 974902, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091252

RESUMO

This study aimed to characterize metabolite differences and correlations between hypertensive disorders of pregnancy (HP) and gestational diabetes mellitus (GDM) using univariate, multivariate analyses, RF, and pathway analyses in a cross-sectional study. Dietary surveys were collected and targeted metabolomics was applied to measure levels of serum fatty acids, amino acids, and organic acids in 90 pregnant women at 24-28 weeks gestation at the First Affiliated Hospital of Harbin Medical University. Principal components analysis (PCA) and partial least squares-discriminatory analysis (PLS-DA) models were established to distinguish HP, GDM, and healthy, pregnant control individuals. Univariate and multivariate statistical analyses and Random Forest (RF) were used to identify and map co-metabolites to corresponding pathways in the disease states. Finally, risk factors for the disease were assessed by receiver operating characteristics (ROC) analysis. Dietary survey results showed that HP and GDM patients consumed a high-energy diet and the latter also consumed a high-carbohydrate and high-fat diet. Univariate analysis of clinical indices revealed HP and GDM patients had glycolipid disorders, with the former possessing more severe organ dysfunction. Subsequently, co-areas with significant differences identified by basic discriminant analyses and RF revealed lower levels of pyroglutamic acid and higher levels of 2-hydroxybutyric acid and glutamic acid in the GDM group. The number of metabolites increased in the HP group as compared to the healthy pregnant control group, including pyroglutamic acid, γ-aminobutyric acid (GABA), glutamic acid, oleic acid (C18:1), and palmitic acid (C16:0). ROC curves indicated that area under curve (AUC) for pyroglutamic acid in the GDM group was 0.962 (95% CI, 0.920-1.000), and the AUC of joint indicators, including pyroglutamic acid and GABA, in the HP group was 0.972 (95% CI, 0.938-1.000). Collectively, these results show that both GDM and HP patients at mid-gestation possessed dysregulated glucose and lipid metabolism, which may trigger oxidative stress via glutathione metabolism and biosynthesis of unsaturated fatty acids.

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