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1.
Small ; 20(7): e2303946, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37806767

RESUMO

The key to increasing the rate of oxygen evolution reaction (OER) lies in accelerated four-electron dynamics, while the key to facilitating the development of supercapacitors lies in the design of electrode materials. This paper synthesized manganese-iron Prussian blue (MnFe-PBA@IF) at room temperature, and hexagonal concave structures w ere prepared using a fast-reducing matrix. Interestingly, MnFe-PBA@IF has an amorphous structure favorable to exposing more active surfaces. According to Gibbs free energy calculations on MnFe-PBA, charge depletion of manganese atoms can greatly enhance the adsorption of electron-rich oxygen-containing groups on the surface. Furthermore, the overpotential in 1 m KOH is 280 mV. Also, it can be used as a supercapacitor with a stable operating voltage range of -0.9-0 V and a specific capacity of 1260 F g-1 . This work provides new insights into the synthesis of OER catalysts for Prussian blue ferromanganese at room temperature. Non-gold-bonded adsorption, highly active metal centers and active surfaces are the underlying reasons for the superior performance of supercapacitors. Therefore, Prussian blue with good energy storage performance and high active surface can be used as multifunctional energy storage and conversion electrodes.

2.
Ren Fail ; 46(1): 2347462, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38832497

RESUMO

Diabetic nephropathy (DN) is one of the most serious and frequent complications among diabetes patients and presently constitutes vast the cases of end-stage renal disease worldwide. Tubulointerstitial fibrosis is a crucial factor related to the occurrence and progression of DN. Oridonin (Ori) is a diterpenoid derived from rubescens that has diverse pharmacological properties. Our previous study showed that Ori can protect against DN by decreasing the inflammatory response. However, whether Ori can alleviate renal fibrosis in DN remains unknown. Here, we investigated the mechanism through which Ori affects the Wnt/ß-catenin signaling pathway in diabetic rats and human proximal tubular epithelial cells (HK-2) exposed to high glucose (HG) levels. Our results revealed that Ori treatment markedly decreased urinary protein excretion levels, improved renal function and alleviated renal fibrosis in diabetic rats. In vitro, HG treatment increased the migration of HK-2 cells while reducing their viability and proliferation rate, and treatment with Ori reversed these changes. Additionally, the knockdown of ß-catenin arrested cell migration and reduced the expression levels of Wnt/ß-catenin signaling-related molecules (Wnt4, p-GSK3ß and ß-catenin) and fibrosis-related molecules (α-smooth muscle actin, collagen I and fibronectin), and Ori treatment exerted an effect similar to that observed after the knockdown of ß-catenin. Furthermore, the combination of Ori treatment and ß-catenin downregulation exerted more pronounced biological effects than treatment alone. These findings may provide the first line of evidence showing that Ori alleviates fibrosis in DN by inhibiting the Wnt/ß-catenin signaling pathway and thereby reveal a novel therapeutic avenue for treating tubulointerstitial fibrosis.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Diterpenos do Tipo Caurano , Fibrose , Via de Sinalização Wnt , Animais , Humanos , Masculino , Ratos , beta Catenina/metabolismo , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/etiologia , Diterpenos do Tipo Caurano/farmacologia , Diterpenos do Tipo Caurano/uso terapêutico , Fibrose/tratamento farmacológico , Rim/patologia , Rim/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/metabolismo , Ratos Sprague-Dawley , Via de Sinalização Wnt/efeitos dos fármacos
3.
Reproduction ; 165(6): 593-603, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37000598

RESUMO

In brief: The appropriate growth and functions of Sertoli cells are crucial to testis development and spermatogenesis in mammals. This study reveals a novel mechanism of follicle-stimulating hormone in immature porcine Sertoli cell proliferation. Abstract: Follicle-stimulating hormone (FSH) is a major Sertoli cell mitogen that binds to the FSH receptor. Sertoli cells are indispensable for testis development and spermatogenesis. However, the regulatory mechanisms of FSH in immature Sertoli cell proliferation have not been determined, particularly in domestic animals. In the present study, we identified the regulatory mechanisms of FSH during immature porcine Sertoli cell proliferation. Transcriptome analysis revealed 114 differentially expressed genes that were induced by FSH treatment, which contains 68 upregulated and 46 downregulated genes. These differentially expressed genes were enriched in multiple pathways, including the Ras signaling pathway. Knockdown of the CC-chemokine receptor 7 (CCR7) gene, which was upregulated by FSH, inhibited cell cycle progression by arresting cells in the G1 phase and reduced the cell proliferation and ERK1/2 phosphorylation. In addition, Kobe0065 inhibited Ras signaling in a similar manner as CCR7 knockdown. Furthermore, FSH abolished the effects of Ras signaling pathway inhibition and CCR7 knockdown. Collectively, FSH promotes immature porcine Sertoli cell proliferation by activating the CCR7/Ras-ERK signaling axis. Our results provide novel insights into the regulatory mechanism of FSH in porcine testis development and spermatogenesis by deciding the fate of immature porcine Sertoli cells.


Assuntos
Células de Sertoli , Transdução de Sinais , Masculino , Animais , Suínos , Receptores CCR7/metabolismo , Células de Sertoli/metabolismo , Proliferação de Células , Hormônio Foliculoestimulante/farmacologia , Hormônio Foliculoestimulante/metabolismo , Testículo/metabolismo , Mamíferos/metabolismo
4.
Langmuir ; 39(12): 4530-4536, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36919933

RESUMO

Lossless and efficient robotic grasping is becoming increasingly important with the widespread application of intelligent robotics in warehouse transportation, human healthcare, and domestic services. However, current sensors for feedback of grasping behavior are greatly restricted by high manufacturing cost, large volume and mass, complex circuit, and signal crosstalk. To solve these problems, here, we prepare lightweight distance sensor-based reduced graphene oxide (rGO)/MXene-rGO coaxial microfibers with interface buffer to assist lossless grasping of a robotic manipulator. The as-fabricated distance microsensor exhibits a high sensitivity of 91.2 m-1 in the distance range of 50-300 µm, a fast response time of 116 ms, a high resolution of 5 µm, and good stability in 500 cycles. Furthermore, the high-performance and lightweight microsensor is installed on the robotic manipulator to reflect the grasp state by the displacement imposed on the sensor. By establishing the correlation between the microsensing signal and the grasp state, the safe, non-destructive, and effective grasp and release of the target can be achieved. The lightweight and high-powered distance sensor displays great application prospects in intelligent fetching, medical surgery, multi-spindle automatic machines, and cultural relics excavation.

5.
Anal Bioanal Chem ; 415(3): 427-438, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36385304

RESUMO

Nucleic acid amplification tests (NAATs) have become an attractive approach for pathogen detection, and obtaining high-quality nucleic acid extracts from biological samples plays a critical role in ensuring accurate NAATs. In this work, we established an elution-free magnetic bead (MB)-based method by introducing polyethylene-polypropylene glycol (PEPPG) F68 in lysis buffer and using NaOH solution instead of alcohols as the washing buffer for rapid nucleic acid extraction from multiple types of biological samples, including nasopharyngeal swabs, serum, milk, and pork, which bypassed the nucleic acid elution step and allowed the nucleic acid/MB composite to be directly used as the template for amplification reactions. The entire extraction process was able to be completed in approximately 7 min. Even though the nucleic acid/MB composite could not be used for quantitative real-time PCR (qPCR) assays, this elution-free MB-based method significantly improved the sensitivity of the loop-mediated isothermal amplification (LAMP) assay. The sensitivity of the quantitative real-time LAMP (qLAMP) assays combined with this elution-free MB-based method showed an improvement of one to three orders of magnitude compared with qLAMP or qPCR assays combined with the traditional MB-based method. In addition to manual operation, like the traditional MB-based method, this universal, rapid, and facile nucleic acid extraction method also has potential for integration into automated robotic processing, making it particularly suitable for the establishment of an analysis platform for ultrafast and sensitive pathogen detection in various biological samples both in centralized laboratories and at remote sites.


Assuntos
Ácidos Nucleicos , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Fenômenos Magnéticos , Sensibilidade e Especificidade
6.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674895

RESUMO

Calcium/calmodulin-dependent protein kinase (CaMK), a key downstream target protein in the Ca2+ signaling pathway of eukaryotes, plays an important regulatory role in the growth, development and pathogenicity of plant fungi. Three AaCaMKs (AaCaMK1, AaCaMK2 and AaCaMK3) with conserved PKC_like superfamily domains, ATP binding sites and ACT sites have been cloned from Alternaria alternata, However, their regulatory mechanism in A. alternata remains unclear. In this study, the function of the AaCaMKs in the development, infection structure differentiation and pathogenicity of A. alternata was elucidated through targeted gene disruption. The single disruption of AaCaMKs had no impact on the vegetative growth and spore morphology but significantly influenced hyphae growth, sporulation, biomass accumulation and melanin biosynthesis. Further expression analysis revealed that the AaCaMKs were up-regulated during the infection structure differentiation of A. alternata on hydrophobic and pear wax substrates. In vitro and in vivo analysis further revealed that the deletion of a single AaCaMKs gene significantly reduced the A. alternata conidial germination, appressorium formation and infection hyphae formation. In addition, pharmacological analysis confirmed that the CaMK specific inhibitor, KN93, inhibited conidial germination and appressorium formation in A. alternata. Meanwhile, the AaCaMKs genes deficiency significantly reduced the A. alternata pathogenicity. These results demonstrate that AaCaMKs regulate the development, infection structure differentiation and pathogenicity of A. alternata and provide potential targets for new effective fungicides.


Assuntos
Fungicidas Industriais , Pyrus , Pyrus/microbiologia , Virulência/genética , Alternaria , Fungicidas Industriais/farmacologia , Fungicidas Industriais/metabolismo
7.
Anticancer Drugs ; 33(1): e381-e388, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34419956

RESUMO

Glioblastoma has high recurrence, while the sensitivity of recurrent glioblastoma to chemotherapy is lower than that of primary glioblastoma. Moreover, there is no standardized treatment for recurrent glioblastoma. Unfortunately, the biological mechanism of recurrent glioblastoma is still unclear, and there are few related studies. We compared the phenotypes of clinical glioblastoma specimens, in-vitro cultured glioma stem-like cells (GSCs) and patient-derived xenograft tumor (PDX) models to explore the molecular genetic characteristics of primary and recurrent glioblastoma from the same patient. In vitro, SU5-2, GSCs derived from recurrent glioblastoma specimens, had stronger proliferative activity and self-renewal ability. Meanwhile, SU5-2 was more resistant to temozolomide and invasive than SU5-1, which derived from primary glioblastoma specimens. Further analysis of the expression of costimulatory molecules showed that the expression of B7-H1, B7-H2 and B7-H3 of SU5-2 were upregulated. In vivo, Kaplan-Meier survival curve analysis showed that the median survival of the recurrent PDX group was worse. The results of gene detection in vitro, PDX model and clinical samples were consistent. Our results showed that the GSCs based on glioblastoma specimens and the PDX models could replicate the main molecular genetic characteristics of original tumors, which provided a reliable experimental platform for both tumor translation kinds of research and screening of molecular therapeutic targets.


Assuntos
Neoplasias Encefálicas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Glioma/genética , Células-Tronco Neoplásicas/patologia , Animais , Proliferação de Células/fisiologia , Regulação da Expressão Gênica , Glioma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia , Fenótipo , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
J Appl Microbiol ; 133(4): 2631-2641, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35870147

RESUMO

AIMS: Calmodulin (CaM), acts as a kind of multifunctional Ca2+ sensing protein, which is ubiquitous in fungi, is highly conserved across eukaryotes and is involved in the regulation of a range of physiological processes, including morphogenesis, reproduction and secondary metabolites biosynthesis. Our aim was to understand the characteristics and functions of AaCaM in Alternaria alternata, the causal agent of pear black spot. METHODS AND RESULTS: A 450 bp cDNA sequence of AaCaM gene of A. alternata was cloned by the PCR homology method. Sequence analysis showed that this protein encoded by AaCaM was a stable hydrophilic protein and had a high similarity to Neurospora crassa (CAA50271.1) and other fungi. RT-qPCR analysis determined that AaCaM was differentially upregulated during infection structural differentiation of A. alternata both on hydrophobic and pear wax extract-coated surface, with a 3.37-fold upregulation during the hydrophobic induced appressorium formation period (6 h) and a 1.46-fold upregulation during the infection hyphae formation period (8 h) following pear wax induction. Pharmaceutical analysis showed that the CaM-specific inhibitor, trifluoperazine (TFP), inhibited spore germination and appressorium formation, and affected toxins and melanin biosynthesis in A. alternata. CONCLUSIONS: AaCaM plays an important role in regulating infection structure differentiation and secondary metabolism of A. alternata. SIGNIFICANCE AND IMPACT OF STUDY: Our study provides a theoretical basis for further in-depth investigation of the specific role of AaCaM in the calcium signalling pathway underlying hydrophobic and pear wax-induced infection structure differentiation and pathogenicity of A. alternata.


Assuntos
Pyrus , Alternaria/metabolismo , Cálcio/metabolismo , Calmodulina/genética , Calmodulina/metabolismo , DNA Complementar/metabolismo , Melaninas/metabolismo , Preparações Farmacêuticas , Doenças das Plantas/microbiologia , Pyrus/genética , Pyrus/metabolismo , Pyrus/microbiologia , Trifluoperazina/metabolismo
9.
Phytopathology ; 112(10): 2207-2217, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35612304

RESUMO

Fungal pathogens use plant surface physiochemical signals to trigger specific developmental processes. To assess the role of phospholipase C (PLC) in mediating plant stimuli sensing of Alternaria alternata, the function of three PLC genes was characterized by constructing ΔAaPLC mutants. Here we showed that fruit wax-coated surfaces significantly induced appressorium formation in A. alternata and mutants. Germination of ΔAaPLC mutants did not differ from the wild type. Deletion of AaPLC1 led to the decrease of appressorium formation and infected hyphae, but the degree of reduction varies between the different types of waxes, with the strongest response to pear wax. Appressorium formation and infected hyphae of the ΔAaPLC1 mutant on dewaxed onion epidermis mounted with pear wax (θ4) were reduced by 14.5 and 65.7% after 8 h incubation, while ΔAaPLC2 and ΔAaPLC3 formed the same infection hyphae as wild type. In addition, AaPLC1 mutation caused pleiotropic effects on fungal biological function, including growth deficiency, changes in stress tolerance, weakening of pathogenicity to the host, as well as destruction of mycotoxin synthesis. Both AaPLC2 and AaPLC3 genes were found to have some effects on stress response and mycotoxin production. Taken together, AaPLC genes differentially regulate the growth, stress response, pathogenicity, and secondary metabolism of A. alternata.


Assuntos
Micotoxinas , Pyrus , Alternaria/genética , Frutas , Micotoxinas/metabolismo , Doenças das Plantas/microbiologia , Pyrus/microbiologia , Metabolismo Secundário , Fosfolipases Tipo C/genética , Fosfolipases Tipo C/metabolismo , Virulência , Ceras/metabolismo
10.
Nanomedicine ; 45: 102592, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35905842

RESUMO

The low delivery efficiency of nano-drugs and limited tumour penetration are still huge challenges in treating solid tumours. Herein, we developed a pH-responsive nano-drug delivery system, CALS/PDMA@DOX, with a size conversion-layered delivery function. The system is composed of a pH-responsive cationic liposome loaded with DOX (CALS) and a polyamidoamine dendrimer loaded with DOX (PAMAM@DOX) modified with 2,3-dimethylmaleic anhydride (PDMA@DOX) using electrostatic adsorption. In the tumour microenvironment, the positively-charged large-size CALS and the positively-charged small-size PAMAM@DOX were dissociated to exert anti-tumour effects. CALS preferentially targeted tumour angiogenesis endothelial cells. Because of its small size and positive charge, PAMAM@DOX showed excellent tumour penetration. Significant tumour suppression by the system in vivo was confirmed in a 4T1 tumour xenograft mouse model. This pH-triggered size-switching layered delivery nanosystem is a safe and effective cancer treatment delivery platform that improves drug permeability and therapeutic efficacy.


Assuntos
Dendrímeros , Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Células Endoteliais/patologia , Humanos , Concentração de Íons de Hidrogênio , Lipossomos , Camundongos , Sistemas de Liberação de Fármacos por Nanopartículas , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente Tumoral
11.
Ecotoxicol Environ Saf ; 241: 113822, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35777343

RESUMO

Nonylphenol (NP) is an endocrine disruptor with reproductive toxicity, which can induce apoptosis of Sertoli cells (SCs). SCs have a high aerobic glycolytic flux to ensure sufficient lactate for germ cells as central energy metabolite, and hypoxia-inducible factors 1alpha (HIF-1α) is a major regulator of glycolysis. This study aimed to investigate whether NP can alter HIF-1α-regulated aerobic glycolysis metabolism and thus induce apoptosis in rat SCs. The results revealed that cell viability, intracellular and extracellular lactate levels, the expression of Hk2, Ldha and Mct4, and the protein levels of HIF-1α, HK2, LDHA and MCT4 were decreased significantly when rat SCs exposed to 20 and 30 µM NP for 24 h. Compared with the 30 µM NP group, the protein levels of HIF-1α, HK2 and LDHA, the expression of Hk2 and Ldha and intracellular lactate levels were increased in 30 µM NP and 125 µM cobalt chloride (CoCl2, inhibitor of HIF-1α proteasome-mediated degradation) co-treated group. Furthermore, the elevation of reactive oxygen species (ROS) and apoptosis induced by 30 µM NP were also reversed. In summary, exposure to NP inhibited the ability of SCs to produce and secrete lactate. Meanwhile, NP exposure could lead to a decrease in HIF-1α thereby inhibiting aerobic glycolysis in rat SCs, disrupting intracellular homeostasis and further inducing ROS-mediated apoptosis. This research is the first to explore the NP toxicity on SCs function with respect to nutrition support to germ cells, and provide new evidence on the inhibition of aerobic glycolysis inducing ROS-mediated apoptosis in SCs.


Assuntos
Apoptose , Células de Sertoli , Animais , Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lactato Desidrogenase 5 , Lactatos/metabolismo , Masculino , Fenóis , Ratos , Espécies Reativas de Oxigênio/metabolismo , Células de Sertoli/metabolismo
12.
Int J Mol Sci ; 23(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36555577

RESUMO

Previous research shows that ginsenoside Rb3 (G-Rb3) exhibit significant protective effects on cardiomyocytes and is considered a promising treatment for myocardial infraction (MI). However, how to improve its oral bioavailability and reduce its dosage remains to be studied. Previous studies suggest that Ferruginol (FGL) may have synergistic effects with G-Rb3. However, the underlying mechanisms remain to be explored. In this study, left anterior descending branch (LAD) coronary artery ligation or oxygen-glucose deprivation-reperfusion (OGD/R) were used to establish MI models in vivo and in vitro. Subsequently, the pharmacological effects and mechanisms of G-Rb3-FGL were explored by in vitro studies. The results showed that the G-Rb3-FGL co-treatment improved heart functions better than the G-Rb3 treatment alone in MI mice models. Meanwhile, the G-Rb3-FGL co-treatment can upregulate fatty acids oxidation (FAO) and suppress oxidative stress in the heart tissues of MI mice. In vitro studies demonstrated that the synergistic effect of G-Rb3-FGL on FAO, oxidation and inflammation was abolished by RXRα inhibitor HX531 in the H9C2 cell model. In summary, we revealed that G-Rb3 and FGL have a synergistic effect against MI. They protected cardiomyocytes by promoting FAO, inhibiting oxidative stress, and suppressing inflammation through the RXRα-Nrf2 signaling pathway.


Assuntos
Infarto do Miocárdio , Camundongos , Animais , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Inflamação/metabolismo
13.
Mol Pharm ; 18(8): 3026-3036, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34213912

RESUMO

Breast cancer is one of the most common malignant tumors in women. The existence of multiple breast cancer subtypes often leads to chemotherapy failure or the development of drug resistance. In recent years, photodynamic therapy has been proven to enhance the sensitivity of tumors to chemotherapeutic drugs. Porphyrin-based metal-organic framework (MOF) materials could simultaneously be used as carriers for chemotherapy and photosensitizers in photodynamic therapy. In this paper, doxorubicin hydrochloride (DOX) was loaded in porphyrin MOFs, and the mechanism of the synergistic effect of the DOX carriers and photodynamic therapy on breast cancer was investigated. In vitro and in vivo experiments have shown that MOFs could prolong the residence time of DOX in tumor tissues and promote the endocytosis of DOX by tumor cells. In addition, adjuvant treatment with photodynamic therapy can promote breast cancer tumors to resensitize to DOX and synergistically enhance the chemotherapy effect of DOX. Therefore, this study can provide effective development ideas for reversing drug resistance during breast cancer chemotherapy and improving the therapeutic effect of chemotherapy on breast cancer.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Doxorrubicina/administração & dosagem , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Sistemas de Liberação de Fármacos por Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Animais , Antibióticos Antineoplásicos/farmacocinética , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Porfirinas/química , Distribuição Tecidual/efeitos dos fármacos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
14.
Mol Cell Biochem ; 476(10): 3591-3600, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34019202

RESUMO

Bone morphogenetic protein 9 (BMP9) is a recently discovered cytokine mainly secreted by the liver and is a member of the transforming growth factor ß (TGF-ß) superfamily. In recent years, an increasing number of studies have shown that BMP9 is associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC), and BMP9 signaling may play dual roles in liver diseases. In this review, we mainly summarized and discussed the roles and potential mechanisms of BMP9 signaling in NAFLD, liver fibrosis and HCC. Specifically, this article will provide a better understanding of BMP9 signaling and new clues for the treatment of liver diseases.


Assuntos
Fator 2 de Diferenciação de Crescimento/metabolismo , Hepatopatias/metabolismo , Transdução de Sinais , Animais , Humanos , Hepatopatias/patologia , Hepatopatias/terapia
15.
Molecules ; 26(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800264

RESUMO

Cardiotoxicity is one of the main side effects of doxorubicin (Dox) treatment. Dox could induce oxidative stress, leading to an opening of the mitochondrial permeability transition pore (mPTP) and apoptosis in cardiomyocytes. Previous studies have shown that Cryptotanshinone (Cts) has potential cardioprotective effects, but its role in Dox-induced cardiotoxicity (DIC) remains unknown. A Dox-stimulated H9C2 cell model was established. The effects of Cts on cell viability, reactive oxygen species (ROS), superoxide ion accumulation, apoptosis and mitochondrial membrane potential (MMP) were evaluated. Expressions of proteins in Akt-GSK-3ß pathway were detected by Western blot. An Akt inhibitor was applied to investigate the effects of Cts on the Akt-GSK-3ß pathway. The effects of Cts on the binding of p-GSK-3ß to ANT and the formation of the ANT-CypD complex were explored by immunoprecipitation assay. The results showed that Cts could increase cell viability, reduce ROS levels, inhibit apoptosis and protect mitochondrial membrane integrity. Cts increased phosphorylated levels of Akt and GSK-3ß. After cells were co-treated with an Akt inhibitor, the effects of Cts were abolished. An immunoprecipitation assay showed that Cts significantly increased GSK-3ß-ANT interaction and attenuated Dox-induced formation of the ANT-CypD complex, thereby inhibiting opening of the mPTP. In conclusion, Cts could ameliorate oxidative stress and apoptosis via the Akt-GSK-3ß-mPTP pathway.


Assuntos
Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Fenantrenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/efeitos adversos , Doxorrubicina/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Poro de Transição de Permeabilidade Mitocondrial/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenantrenos/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Mol Pharm ; 17(1): 338-348, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31793786

RESUMO

The synergy of chemotherapy and antiangiogenesis therapy is a new strategy for cancer treatment. In this paper, a well-developed core-shell nanoparticle loaded with gambogic acid (GA), heparin (HP), and the immunoadjuvant cytosine-phosphate-guanine oligonucleotide (CpG ODN), called GHC NP, was constructed to treat hepatocellular carcinoma. GHC NPs with liver targeting activity can effectively inhibit tumor cell proliferation and angiogenesis. With the delivery of nanocarriers and the assistance of GA and HP, the GHC NPs can more effectively upregulate cytotoxic T cell (CTL) levels, promote helper T cell (Th cell) differentiation, and induce Th1 immune responses in long-term treatment compared with single CpG ODN. This synergistically enhanced immunotherapy might have universal application in cancer treatments.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas Experimentais/terapia , Neoplasias Hepáticas/terapia , Nanopartículas/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Células Hep G2 , Heparina/administração & dosagem , Humanos , Imunoterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Camundongos , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanopartículas/ultraestrutura , Oligodesoxirribonucleotídeos/administração & dosagem , Células RAW 264.7 , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Xantonas/administração & dosagem
17.
Toxicol Ind Health ; 36(11): 925-935, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33025838

RESUMO

Our previous studies have shown that continuous exposure to nonylphenol (NP) may cause female reproductive toxicity even at low doses. To better understand this toxic effect, the aim of this study was to investigate the basic characteristics of the disposal kinetics of NP under a chronic exposure scenario to simulate human exposure. Female rats were exposed to NP at three dose levels (50-, 500-, and 10,000 µg kg-1 bw day-1, low, medium, and high dose, respectively) by gavage daily for 17 weeks. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used to detect NP in rat sera and tissues. The results suggested that a two extravascular compartment model was found to better match the actual serum metabolic behavior of NP. Compared with the high-dose group, the NP absorption in the low-dose group was relatively efficient, the clearance rate was slower, and the residual amount of NP was greater. NP was found mostly in the uterus, adipose and brain tissues and to a lesser degree, in the liver, kidney, and ovary. The results indicated that the extensive organ distribution may cause corresponding toxicity even at relatively low doses.


Assuntos
Fenóis/farmacocinética , Animais , Relação Dose-Resposta a Droga , Feminino , Taxa de Depuração Metabólica , Modelos Biológicos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Toxicocinética
18.
Pharmazie ; 75(1): 18-22, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-32033628

RESUMO

Salvia miltiorrhiza (Danshen) is typically used in the treatment of diabetic complications and is often co-prescribed with gliquidone in China. However, whether danshen affects the absorption of gliquidone has not been elucidated. In this study, the effects of an aqueous extract of danshen (danshen injection, DSI) and its primary compounds (danshensu, protocatechuic aldehyde, rosmarinic acid and salvianolic acid B) on gliquidone transport across Caco-2 monolayer cells was investigated. DSI enhanced the transport of gliquidone in Caco-2 cell monolayers from the apical (AP) to basolateral (BL) sides and from the BL to AP sides. Rosmarinic acid (RA) also significantly increased the Papp (AP-BL) value for gliquidone transport. Verapamil (a P-gp inhibitor) and Ko143 (a BCRP inhibitor) inhibited the BL-AP transport of gliquidone and promoted the AP-BL transport of gliquidone, whereas MK571 (an MRP1 inhibitor), probenecid (an MRP2 inhibitor), and benzbromarone (an MRP3 inhibitor) had no effect on gliquidone transport. RA also enhanced the intracellular accumulation of Rho123 and Hoechst 33342. The expression of P-gp and BCRP was significantly downregulated, and P-gp ATPase activity was promoted by RA in a dose-dependent manner. These results indicate that an aqueous extract of danshen can increase the transport of gliquidone in Caco-2 cell monolayers and that RA may be the primary compound associated with this activity, which is in agreement with RA simultaneously suppressing the function and expression of P-gp and BCRP.


Assuntos
Cinamatos/farmacologia , Depsídeos/farmacologia , Extratos Vegetais/farmacologia , Salvia miltiorrhiza/química , Compostos de Sulfonilureia/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Transporte Biológico , Células CACO-2 , Cinamatos/administração & dosagem , Cinamatos/isolamento & purificação , Depsídeos/administração & dosagem , Depsídeos/isolamento & purificação , Relação Dose-Resposta a Droga , Interações Medicamentosas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Neoplasias/genética , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ácido Rosmarínico
19.
Small ; 15(47): e1903977, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31608586

RESUMO

Black phosphorous quantum dots (BPQDs) possess ambipolar charge transport, high mobility, and a tunable direct bandgap. Here, liquid-exfoliated BPQDs are used as interlayers to modify both the electron transport layer and hole transport layer in organic solar cells (OSCs). The incorporation of BPQDs is beneficial to the formation of a cascade band structure and electron/hole transfer and extraction. The power conversion efficiency of the BPQDs-incorporated OSC based on PTB7-Th:FOIC blend is enhanced from 11.8% to 13.1%. In addition, power conversion efficiency enhancement is also achieved for other nonfullerene and fullerene-based devices, demonstrating the universality of this interlayer methodology.

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