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1.
Int J Obes (Lond) ; 48(6): 849-858, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38341506

RESUMO

OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.


Assuntos
Encéfalo , Diabetes Gestacional , Dieta Hiperlipídica , Ácidos Graxos , Efeitos Tardios da Exposição Pré-Natal , Animais , Gravidez , Feminino , Diabetes Gestacional/metabolismo , Camundongos , Dieta Hiperlipídica/efeitos adversos , Encéfalo/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Masculino , Ácidos Graxos/metabolismo , Modelos Animais de Doenças , Fenômenos Fisiológicos da Nutrição Materna
2.
Endocr J ; 71(8): 753-765, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38777757

RESUMO

Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: -0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: -0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.


Assuntos
Hidrocortisona , Privação do Sono , Privação do Sono/sangue , Hidrocortisona/sangue , Humanos
3.
J Enzyme Inhib Med Chem ; 39(1): 2295241, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38134358

RESUMO

Colorectal cancer (CRC) is one of the most common cancers worldwide. Nowadays, owing to the complex mechanism of tumorigenesis, simultaneous inhibition of multiple targets is an important anticancer strategy. Recent studies have demonstrated receptor tyrosine kinase AXL (AXL) and histone deacetylase 2 (HDAC2) are closely associated with colorectal cancer. Herein, we identified five hit compounds concurrently targeting AXL and HDAC2 using virtual screening. Inhibitory experiments revealed these hit compounds potently inhibited AXL and HDAC2 in the nanomolar range. Among them, Hit-3 showed the strongest inhibitory effects which were better than that of the positive control groups. Additionally, MD assays showed that Hit-3 could bind stably to the AXL and HDAC2 active pockets. Further MTT assays demonstrated that Hit-3 showed potent anti-proliferative activity. Most importantly, Hit-3 exhibited significant in vivo antitumor efficacy in xenograft models. Collectively, this study is the first discovery of dual-targeting AXL/HDAC2 inhibitors for colorectal cancer treatment.


Assuntos
Neoplasias Colorretais , Simulação de Dinâmica Molecular , Humanos , Simulação de Acoplamento Molecular , Farmacóforo , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Detecção Precoce de Câncer , Neoplasias Colorretais/tratamento farmacológico
4.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3868-3877, 2024 Jul.
Artigo em Zh | MEDLINE | ID: mdl-39099360

RESUMO

The study investigated the effect of Compound Shougong Powder(CSGP) on the biological functions of triple-negative breast cancer(TNBC) cells and whether its mechanism of action was related to the epithelial-mesenchymal transition(EMT) signaling pathway. TNBC cells(MDA-MB-231 and BT-549) were treated with different concentrations of CSGP-containing serum. MTS assay was used to detect the effect of CSGP on the proliferation of TNBC cells. The EdU staining was used to detect the effect of CSGP on the proliferation of TNBC cells. Flow cytometry was used to examine the impact of CSGP on apoptosis of TNBC cells. Wound-healing and Transwell assays were used to evaluate the effects of different concentrations of CSGP on the migration and invasion capabilities of TNBC cells. RNA sequencing technology was utilized to elucidate its mechanism. Subsequently, qRT-PCR was performed to measure the mRNA expression levels of E-cadherin, N-cadherin, Slug, Snail, Vimentin, Twist, Zinc finger E-box-Binding homeobox 1(Zeb1), and Zinc finger E-box-Binding homeobox 2(Zeb2). Western blot was used to assess the protein expression levels of Slug, Vimentin, and E-cadherin. After intervention with CSGP, the proliferation of MDA-MB-231 and BT-549 cells significantly decreased, while the apoptosis rate markedly increased. The expression levels of the epithelial marker protein E-cadherin significantly increased, while the expression levels of the EMT-related transcription factors Slug and Vimentin showed a decrease. In conclusion, CSGP inhibits the EMT, thereby suppressing the malignant progression of TNBC.


Assuntos
Apoptose , Proliferação de Células , Medicamentos de Ervas Chinesas , Transição Epitelial-Mesenquimal , Neoplasias de Mama Triplo Negativas , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Medicamentos de Ervas Chinesas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Pós/química , Caderinas/genética , Caderinas/metabolismo
5.
Analyst ; 148(22): 5667-5672, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37812430

RESUMO

The study of cellular responses linked to oxidative stress mechanisms is crucial in comprehending diverse physiological and pathological life processes, including mitochondrial dysfunction. Nonetheless, despite the interference of O2, the monitoring of ROS released from cells poses a challenging task. In this study, carbon-based copper single-atom catalysts (Cu SACs) were synthesized that exhibits excellent electrocatalytic performance for H2O2 reduction with an initial potential at 0.23 V and effectively avoids interference from O2. Based on this catalyst, a flexible and stretchable oxygen-tolerant sensor was constructed and applied to monitor the calcium ion-induced ROS burst in human umbilical vein endothelial cells (HUVECs) in a simulated physiological condition. This study effectively eradicates interference that may arise from the reduction of O2 and presents a dependable platform for real-time in situ monitoring of physiologically active molecules by utilizing H2O2 detection.


Assuntos
Peróxido de Hidrogênio , Oxigênio , Humanos , Peróxido de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio , Cobre/química , Células Endoteliais da Veia Umbilical Humana
6.
Environ Res ; 224: 115447, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36758919

RESUMO

A green, high-efficiency, and wide pH tolerance water remediation process has been urgently acquired for the increasingly exacerbating contaminated water. In this study, a Fe3+/persulfate (Fe3+/PS) system was employed and enhanced with a green natural ligand cysteine (Cys) for the degradation of quinclorac (QNC). The introduction of Cys into the Fe3+/PS system widened the effective pH range to 9 with a superior removal rate for QNC. The mechanism revealed that the Fe3+/Cys/PS system can enhance the ability of degrading QNC by accelerating the Fe3+/Fe2+ redox cycle, maintaining Fe2+ concentration and thereby generating more HO• and SO4•-. The impact factors (i.e., pH, concentrations of PS, Fe3+ and Cys) were optimized as well. This work provides a promising strategy with high catalytic activity and wide pH tolerance for organic contaminated water remediation.


Assuntos
Quinolinas , Poluentes Químicos da Água , Purificação da Água , Cisteína/química , Concentração de Íons de Hidrogênio , Oxirredução , Água , Poluentes Químicos da Água/análise , Química Verde
7.
Analyst ; 147(18): 4055-4062, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-35968779

RESUMO

Cell mechanotransduction plays an important role in vascular regulation and disease development. Excessive accumulation of ROS, especially superoxide anion radicals (O2˙-), is closely related to cardiovascular diseases. Lately, NADPH oxidases, which are the major source of O2˙- production in vascular tissues, have been demonstrated to be involved in cardiovascular diseases. Therefore, in situ and real-time monitoring of superoxide anions (O2˙-) is essential for exploring the mechanisms of mechanotransduction associated with NADPH oxidase function in living cells. Here we report a rationally designed ultrasonication-assisted approach for growing Au nanoflower films on a flexible surface, which serves as the desired interface for cysteine and superoxide dismutase (SOD) anchoring to form a flexible and stretchable electrode (SOD/Cys/Au SE). The SOD/Cys/Au SE shows good stretchability, fast electron-transfer rates, and high selectivity to measure O2˙- released from cells during the stretching states. Our strategy provides a basis for developing more sophisticated stretchable biosensing tools to induce and monitor transient biochemical signals during cell mechanotransduction.


Assuntos
Técnicas Biossensoriais , Doenças Cardiovasculares , Humanos , Mecanotransdução Celular , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo
8.
Mar Drugs ; 21(1)2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36662191

RESUMO

Fucoidan is a sulfated algal polyanionic polysaccharide that possesses many biological activities. In this paper, a fucoidan (SHF) polysaccharide was extracted from Sargassum hemiphyllum collected in the South China Sea. The SHF, with a molecular weight of 1166.48 kDa (44.06%, w/w), consisted of glucose (32.68%, w/w), galactose (24.81%, w/w), fucose (20.75%, w/w), xylose (6.98%, w/w), mannose (2.76%, w/w), other neutral monosaccharides, and three uronic acids, including glucuronic acid (5.39%, w/w), mannuronic acid (1.76%, w/w), and guronuronic acid (1.76%, w/w). The SHF exhibited excellent immunostimulatory activity. An immunostimulating assay showed that SHF could significantly increase NO secretion in macrophage RAW 264.7 cells via upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) levels based on both gene expression and protein abundance. These results suggest that SHF isolated from Sargassum hemiphyllum has great potential to act as a health-boosting ingredient in the pharmaceutical and functional-food fields.


Assuntos
Sargassum , Sargassum/química , Polissacarídeos/química , Monossacarídeos/química , Macrófagos
9.
Biomed Chromatogr ; 36(8): e5395, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35514216

RESUMO

A rapid, selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to detect meloxicam in human plasma. A triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source was used in positive ion mode. Protein precipitation with acetonitrile was used for sample preparation. Meloxicam and 13 C6 -meloxicam internal standard were analyzed on an Acquity CSH C18 column with a mobile phase of acetonitrile and water in 0.1% formic acid using a gradient program for separation. The retention time of meloxicam was 1.1 min and the total run time was only 2.0 min. Detection was performed in multiple reaction monitoring mode using an electrospray ionization source with optimized mass spectrometry parameters. The calibration curves were linear in the range 10.0-3.00 × 103 ng/ml (r ≥ 0.99). The within-run and between-run RSDs were ≤14.8%. The within-run and between-run REs ranged from -4.6 to 10.7%. There was no significant matrix effect, and the recovery rate was high. This method was fully validated, including reinjection reproducibility in human plasma. The method was applied to the pharmacokinetic study. All of the incurred sample reanalysis methods met the criteria.


Assuntos
Espectrometria de Massas em Tandem , Acetonitrilas , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Meloxicam , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
10.
Entropy (Basel) ; 24(4)2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35455200

RESUMO

Full-duplex (FD) transmission holds a great potential of improving the sum data rate of wireless communication systems. However, the self-interference introduced by the full-duplex transmitter brings a big challenge to enhance the energy efficiency. This paper investigates the power allocation problem in a full-duplex two-way (FDTW) communication network over an OFDM channel, aiming at improving the sum data rate and energy efficiency. We first characterize the sum rate and energy efficiency achieved in a single-carrier FDTW system. The optimal transmit power that achieves the maximal sum data rate is presented. The energy efficiency maximization problem is solved by using fractional programming. Then we further formulate sum rate and energy efficiency maximization problem in a multi-subcarrier FDTW system. In particular, the sub-optimal transmit power allocation which achieves a decent sum rate improvement is found by using a proposed iterative algorithm. By combining the iterative algorithm and fractional programming, we further maximize the energy efficiency of the multi-subcarrier system. With our proposed algorithm, we can easily obtain an optimal transmit power that approximates the global optimal solution. Simulation results show that using the obtained optimal transmit power allocation algorithm can significantly improve the sum rate and energy efficiency in both single-carrier and multi-subcarrier systems.

11.
J Environ Sci (China) ; 112: 170-179, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34955201

RESUMO

The capping is called passive remediation because the sedimentary P was released and then immobilized by the capping materials. However, the release depends on the environmental conditions. Therefore, a hypothesis was proposed that the oxidant was used to accelerate sedimentary P release and the capping material was used to capture those released P. It is positive remediation to reduce sedimentary P amount. The results show that soluble reactive phosphorus (SRP) concentration in the overlying water and pore water increased and then decreased gradually under the combination of sodium percarbonate (SPC) and Ca(OH)2, similar as that under the capping with single Ca(OH)2. The sedimentary P amount was reduced considerably and P concentration in the capping layer increased obviously after 60 days, compared with the capping with single Ca(OH)2. All these indicated that oxidation improved the sedimentary P release and the released P was captured and immobilized by the capping material of Ca(OH)2. However, the acceleration of sedimentary P release due to the oxidation is obviously different from the traditional mechanism that the oxic condition in the sediment is favor of the immobilization on sedimentary P. It is attributed to the oxidizability of ·OH from SPC. The reduction of mobile-P and the increase of Ca-P under the combined use are observed. This is similar as traditional mechanism of oxic condition. It is sure that positive remediation reduced sedimentary P amount, resulting in the decrease of P release risk in a long time.


Assuntos
Sedimentos Geológicos , Poluentes Químicos da Água , Hidróxido de Cálcio , Peróxido de Hidrogênio , Fósforo , Poluentes Químicos da Água/análise
12.
Entropy (Basel) ; 23(8)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34441195

RESUMO

With the rapid development and wide application of the Internet of Things (IoT), how to provide timely and fresh information for strategic analysis and decision-making has become a key issue. Recent studies have shown that preemption strategies are of great importance to the improvement of information freshness. In view of this, we focus on the multi-source preemptive queuing model and investigate how to control the generation rate of each source to achieve the optimal overall information freshness. Specifically, we consider two typical preemption strategies: self-preemption strategy and global-preemption strategy. Noting that the urgency requirements of the systems on the data of each source are different, we propose the weighted average age of information (AoI) to characterize the overall information freshness of the system. For the self-preemption strategy, we prove that the optimal generation rate allocation is a convex problem and present an efficient algorithm to find the optimal solution. Additionally, we also derive a closed-form approximate optimal solution under light load cases to meet the demands for rapid deployment. For the global-preemption strategy, we directly derive the closed-form optimal solution of the corresponding problem. By comparing the optimized weighted average AoIs, the performance achieved by the global-preemption system was better than that achieved by the self-preemption system in terms of the overall timeliness. The numerical analysis verified the correctness of the theoretical analysis and that the proposed approximate solution had high accuracy not only under light load cases but also under other cases.

13.
J Environ Sci (China) ; 82: 93-102, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31133273

RESUMO

Nanoscale zero-valent iron (nZVI) particles supported on a porous, semi-interpenetrating (semi-IPN), temperature-sensitive composite hydrogel (PNIPAm-PHEMA). nZVI@PNIPAm-PHEMA, was successfully synthesized and characterized by FT-IR, SEM, EDS, XRD and the weighing method. The loading of nZVI was 0.1548 ±â€¯0.0015 g/g and the particle size was 30-100 nm. NZVI was uniformly dispersed on the pore walls inside the PNIPAm-PHEMA. Because of the well-dispersed nZVI, the highly porous structure, and the synergistic effect of PNIPAm-PHEMA, nZVI@PNIPAm-PHEMA showed excellent reductive activity and wide pH applicability. 95% of 4-NP in 100 mL of 400 mg/L 4-NP solution with initial pH 3.0-9.0 could be completely reduced into 4-AP by about 0.0548 g of fresh supported nZVI at 18-25 °C under stirring (110 r/min) within 45 min reaction time. A greater than 99% 4-NP degradation ratio was obtained when the initial pH was 5.0-9.0. The reduction of 4-NP by nZVI@PNIPAm-PHEMA was in agreement with the pseudo-first-order kinetics model with Kobs values of 0.0885-0.101 min-1. NZVI@PNIPAm-PHEMA was able to be recycled, and about 85% degradation ratio of 4-NP was obtained after its sixth reuse cycle. According to the temperature sensitivity of PNIPAm-PHEMA, nZVI@PNIPAm-PHEMA exhibited very good storage stability, and about 88.9% degradation ratio of 4-NP was obtained after its storage for 30 days. The hybrid reducer was highly efficient for the reduction of 2-NP, 3-NP, 2-chloro-4-nitrophenol and 2-chloro-4-nitrophenol. Our results suggest that PNIPAm-PHEMA could be a good potential carrier, with nZVI@PNIPAm-PHEMA having potential value in the application of reductive degradation of nitrophenol pollutants.


Assuntos
Nitrofenóis/química , Poluentes Químicos da Água/química , Adsorção , Hidrogéis/química , Ferro/química , Oxirredução , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
14.
J Obstet Gynaecol Res ; 40(9): 2058-65, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25181626

RESUMO

AIM: The purpose of the present study was to explore variation and prognostic significance of serum plasminogen activator inhibitor-1 (PAI-1) before the first cycle of chemotherapy and after the sixth cycle of chemotherapy in epithelial ovarian cancer (EOC) patients who had undergone cytoreductive surgery. MATERIAL AND METHODS: We retrospectively evaluated the serum PAI-1 level of EOC patients and healthy controls and investigated the correlation between both serum PAI-1 levels of EOC patients we detected and clinicopathological characteristics. Survival rates were analyzed by using the Kaplan-Meier technique and Cox regression model. RESULTS: Serum PAI-1 levels of EOC patients before the first cycle of chemotherapy and after the sixth cycle of chemotherapy were significantly higher than those of healthy controls (both P < 0.05). The results of Kaplan-Meier analysis indicated that both serum PAI-1 levels of EOC patients were associated with progression-free survival and overall survival. Multivariate Cox regression analysis revealed the PAI-1 level before the first cycle of chemotherapy was an independent prognostic marker of progression-free survival (28.4 vs 49.6 months; P = 0.013) and overall survival (41.8 vs 53.8 months; P = 0.043). CONCLUSIONS: Both serum PAI-1 levels of EOC patients we detected were associated with International Federation of Gynecology and Obstetrics stage, residual tumor size and lymph node metastasis. The serum PAI-1 level before the first cycle of chemotherapy is an independent predictor for EOC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Inibidor 1 de Ativador de Plasminogênio/sangue , Adulto , Idoso , Biomarcadores/sangue , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante , China/epidemiologia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/sangue , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Paclitaxel/uso terapêutico , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
15.
Front Neurol ; 15: 1416557, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994489

RESUMO

The abuse of nitrous oxide (N2O) poses a substantial public health challenge. In many countries, including China, regulations governing the utilization and accessibility to N2O remain ambiguous, particularly within the food industry. Here, we report a case of a 21-year-old female who presented with symptoms of subacute combined degeneration (SCD) of the spinal cord due to N2O abuse. The patient exhibited bilateral lower limb numbness and weakness, low serum vitamin B12 levels with elevated homocysteine levels, and lumbar spine magnetic resonance imaging (MRI) revealed abnormal signals of the spinal cord. Following cessation of N2O and comprehensive therapy including methylcobalamin and nerve growth factor, the symptoms significantly improved. A follow-up examination 3 months later showed good progress in gait stability. At a 5-year follow-up, the patient's previous clinical symptoms had completely disappeared, and her quality of life had returned to normal. This case underscores the urgency of raising awareness and prevention of N2O abuse, emphasizing the importance of timely diagnosis and comprehensive treatment for patient recovery. Clear formulation and enforcement of relevant regulatory measures are equally crucial in reducing instances of abuse.

16.
Adv Healthc Mater ; 13(5): e2302480, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063347

RESUMO

Single-atom (SA) nanoparticles exhibit considerable potential in terms of photothermal properties for bactericidal applications. Nevertheless, the restricted efficacy of their targeted and controlled antibacterial activity has hindered their practical implementation. This study aims to overcome this obstacle by employing chemical modifications to tailor SAs, thereby achieving targeted and light-controlled antimicrobial effects. By conducting atomic-level modifications on palladium SAs using glutathione (GSH) and mercaptophenylboronic acid (MBA), their superior targeted binding capabilities toward Escherichia coli cells are demonstrated, surpassing those of SAs modified with cysteine (Cys). Moreover, these modified SAs effectively inhibit wound bacteria proliferation and promote wound healing in rats, without inducing noticeable toxicity to major organs under 808 nm laser irradiation. This study highlights the significance of chemical engineering in tailoring the antibacterial properties of SA nanoparticles, opening avenues for combating bacterial infections and advancing nanoparticle-based therapies.


Assuntos
Anti-Infecciosos , Nanopartículas , Ratos , Animais , Nanopartículas/química , Antibacterianos/química
17.
J Colloid Interface Sci ; 670: 279-287, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763024

RESUMO

Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy.


Assuntos
Antineoplásicos , Glutationa , Nanopartículas , Fotoquimioterapia , Pró-Fármacos , Espécies Reativas de Oxigênio , Glutationa/metabolismo , Glutationa/química , Nanopartículas/química , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Camundongos , Ensaios de Seleção de Medicamentos Antitumorais , Tamanho da Partícula , Peróxido de Hidrogênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Propriedades de Superfície , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Microambiente Tumoral/efeitos dos fármacos , Indolquinonas
18.
Mol Nutr Food Res ; 68(19): e2400386, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39246092

RESUMO

SCOPE: This research examines the effects of maternal high-fat (HF) diet and gestational diabetes mellitus (GDM) on offspring lipid metabolism and polyunsaturated fatty acids (PUFA) profile. METHODS AND RESULTS: GDM is induced using the insulin receptor antagonist S961. Weaning offspring are categorized into HF-GDM, HF-CON, NC-GDM, and NC-CON groups based on maternal diet or GDM. Adult offspring are then grouped into NC-CON-NC, NC-CON-HF, NC-GDM-NC, NC-GDM-HF, HF-CON-NC, HF-CON-HF, HF-GDM-NC, and HF-GDM-HF according to dietary patterns. Gas chromatography determines PUFA composition. Western blot assesses PI3K/Akt signaling pathway-related protein expression. Feeding a normal chow diet until adulthood improves the distribution of hepatic PUFA during weaning across the four groups. PI3K expression is upregulated during weaning in HF-CON and HF-GDM, particularly in HF-CON-NC and HF-GDM-NC, compared to NC-CON-NC during adulthood. Akt expression increases in NC-GDM-NC after weaning with a normal diet. The hepatic PUFA profile in HF-CON-HF significantly distinguishes among the maternal generation health groups. Maternal HF diet exacerbates the combined impact of maternal GDM and offspring HF diet on hepatic PUFA and PI3K/Akt signaling pathway-related proteins during adulthood. CONCLUSIONS: Early exposure to HF diets and GDM affects hepatic PUFA profiles and PI3K/Akt signaling pathway protein expression in male offspring during weaning and adulthood.


Assuntos
Diabetes Gestacional , Dieta Hiperlipídica , Ácidos Graxos Insaturados , Fígado , Camundongos Endogâmicos C57BL , Efeitos Tardios da Exposição Pré-Natal , Diabetes Gestacional/metabolismo , Gravidez , Feminino , Animais , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Ácidos Graxos Insaturados/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Desmame , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo
19.
Int J Pharm ; 663: 124568, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39137822

RESUMO

Deficiency of endogenous hydrogen peroxide and insufficient intracellular acidity are usually two important factors limiting chemodynamic therapy (CDT). Here we report a glutathione-responsive nanomedicine that can provide a suitable environment for CDT by inhibiting dual-enzymes simultaneously. The nanomedicine is constructed by encapsulation of a novel hydrogen sulfide donor in nanomicelle assembled by glutathione-responsive amphiphilic polymer. In response to intracellular glutathione, the nanomedicine can efficiently release the active ingredients hydrogen sulfide, carbonic anhydrase inhibitor and ferrocene. The hydrogen sulfide can increase the concentrations of hydrogen peroxide and lactic acid by inhibiting catalase and enhancing glycolysis. The carbonic anhydrase inhibitor can further induce intratumoral acidosis by inhibiting the function of carbonic anhydrase IX. Therefore, the nanomedicine can provide more efficient reaction conditions for the ferrocene-mediated Fenton reaction to generate abundant toxic hydroxyl radicals. In vivo results show that the combination of enhanced CDT and acidosis can effectively inhibit tumor growth. This design of nanomedicine provides a promising dual-enzyme inhibiting strategy to enhance antitumor efficacy of CDT.


Assuntos
Acidose , Compostos Ferrosos , Glutationa , Sulfeto de Hidrogênio , Nanomedicina , Animais , Humanos , Acidose/tratamento farmacológico , Nanomedicina/métodos , Linhagem Celular Tumoral , Glutationa/metabolismo , Compostos Ferrosos/química , Compostos Ferrosos/administração & dosagem , Metalocenos/química , Neoplasias/tratamento farmacológico , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/química , Camundongos Endogâmicos BALB C , Peróxido de Hidrogênio , Camundongos , Micelas , Feminino , Nanopartículas/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos Nus , Polímeros/química , Ácido Láctico/química , Anidrase Carbônica IX/antagonistas & inibidores , Anidrase Carbônica IX/metabolismo , Catalase/metabolismo
20.
Front Microbiol ; 14: 1169884, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37303782

RESUMO

Edible fungi are not only delicious but are also rich in nutritional and medicinal value, which is highly sought after by consumers. As the edible fungi industry continues to rapidly advance worldwide, particularly in China, the cultivation of superior and innovative edible fungi strains has become increasingly pivotal. Nevertheless, conventional breeding techniques for edible fungi can be arduous and time-consuming. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) is a powerful tool for molecular breeding due to its ability to mediate high-efficiency and high-precision genome modification, which has been successfully applied to many kinds of edible fungi. In this review, we briefly summarized the working mechanism of the CRISPR/Cas9 system and highlighted the application progress of CRISPR/Cas9-mediated genome-editing technology in edible fungi, including Agaricus bisporus, Ganoderma lucidum, Flammulina filiformis, Ustilago maydis, Pleurotus eryngii, Pleurotus ostreatus, Coprinopsis cinerea, Schizophyllum commune, Cordyceps militaris, and Shiraia bambusicola. Additionally, we discussed the limitations and challenges encountered using CRISPR/Cas9 technology in edible fungi and provided potential solutions. Finally, the applications of CRISPR/Cas9 system for molecular breeding of edible fungi in the future are explored.

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