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1.
Proc Natl Acad Sci U S A ; 121(12): e2315707121, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38489388

RESUMO

KCTD10 belongs to the KCTD (potassiumchannel tetramerization domain) family, many members of which are associated with neuropsychiatric disorders. However, the biological function underlying the association with brain disorders remains to be explored. Here, we reveal that Kctd10 is highly expressed in neuronal progenitors and layer V neurons throughout brain development. Kctd10 deficiency triggers abnormal proliferation and differentiation of neuronal progenitors, reduced deep-layer (especially layer V) neurons, increased upper-layer neurons, and lowered brain size. Mechanistically, we screened and identified a unique KCTD10-interacting protein, KCTD13, associated with neurodevelopmental disorders. KCTD10 mediated the ubiquitination-dependent degradation of KCTD13 and KCTD10 ablation resulted in a considerable increase of KCTD13 expression in the developing cortex. KCTD13 overexpression in neuronal progenitors led to reduced proliferation and abnormal cell distribution, mirroring KCTD10 deficiency. Notably, mice with brain-specific Kctd10 knockout exhibited obvious motor deficits. This study uncovers the physiological function of KCTD10 and provides unique insights into the pathogenesis of neurodevelopmental disorders.


Assuntos
Encefalopatias , Transtornos do Neurodesenvolvimento , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Animais , Camundongos , Proteínas/metabolismo , Encéfalo/metabolismo , Neurônios/metabolismo , Transtornos do Neurodesenvolvimento/genética , Encefalopatias/genética , Neurogênese/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo
2.
Biomater Sci ; 12(2): 270-287, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38175154

RESUMO

Implantable bioelectrodes for regulating and monitoring biological behaviors have become indispensable medical devices in modern healthcare, alleviating pathological symptoms such as epilepsy and arrhythmia, and assisting in reversing conditions such as deafness and blindness. In recent years, developments in the fields of materials science and biomedical engineering have contributed to advances in research on implantable bioelectrodes. However, the foreign body reaction (FBR) is still a major constraint for the long-term application of electrodes. In this paper, four types of commonly used implantable bioelectrodes are reviewed, concentrating on their background, development, and a series of complications caused by FBR after long-term implantation. Strategies for resisting FBRs are then devised in terms of physics, chemistry, and nanotechnology. We analyze the major trends in the future development of implantable bioelectrodes and outline some promising research to optimize the long-term operational stability of electrodes. Although current implantable bioelectrodes have been able to achieve good biocompatibility, low impedance, and low mechanical mismatch and trauma, these devices still face the challenge of FBR. Resistance to FBR is still the key for the long-term effectiveness of bioelectrodes, and a better understanding of the mechanisms of FBR, as well as miniaturization, long-term passivation, and coupling with gene therapy may be the way forward for the next generation of implantable bioelectrodes.


Assuntos
Reação a Corpo Estranho , Próteses e Implantes , Humanos , Eletrodos , Nanotecnologia
3.
Front Pharmacol ; 14: 1239197, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954847

RESUMO

Background: Cynomorium songaricum Rupr. has long been used as an anti-inflammatory, antidepressant, and anti-aging agent in traditional Chinese medicine in Asia. Its ethyl acetate extract (ECS) has been identified as the main antioxidant component with neuroprotective and estrogen-like effects. However, the potential of ECS in treating depression has not been explored yet. Methods: We identified the primary metabolites in ECS in this study using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Network analysis was used to find the potential targets and pathways associated with the anti-neuroinflammatory depression action of the ECS. In addition, we established a corticosterone (CORT)-induced depression mouse model to assess ECS's antidepressant effects by monitoring various behavioral changes (e.g., sucrose preference, forced swimming, tail suspension, and open field tests) and biochemical indices of the hippocampus, and validating the network analysis results. Significant pathways underwent verification through western blotting based on network analysis prediction. Results: Our study demonstrates that ECS possesses significant antidepressant activity. The LC-MS/MS analysis of ECS identified 30 main metabolites, including phloridzin, phlorizin, ursolic acid, and naringenin, as well as other flavonoids, terpenoids, and phenolic acids. These metabolites were found to be associated with 64 candidate target proteins related to neuroinflammatory depression from the database, and ten hub proteins were identified through filtration: CXCL8, ICAM1, NOS2, SELP, TNF, IL6, APP, ACHE, MAOA and ADA. Functional enrichment analyses of the candidate targets revealed their primary roles in regulating cytokine production, inflammatory response, cytokine activity, and tumor necrosis factor receptor binding. In vivo, ECS improved hippocampal neuroinflammation in the mouse model. Specifically, ECS reduced the expression of inflammatory factors in the hippocampus, inhibited M1 microglial cell polarization, and alleviated depression through the regulation of the NF-κB-NLRP3 inflammation pathway. Conclusion: Based on experimental and network analysis, this study revealed for the first time that ECS exerted antidepression effect via anti-neuroinflammation. Our research provides valuable information on the use of ECS as an alternative therapeutic approach for depression.

4.
Front Bioeng Biotechnol ; 11: 1230682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781533

RESUMO

In recent years, bone tissue engineering (BTE) has played an essential role in the repair of bone tissue defects. Although bioactive factors as one component of BTE have great potential to effectively promote cell differentiation and bone regeneration, they are usually not used alone due to their short effective half-lives, high concentrations, etc. The release rate of bioactive factors could be controlled by loading them into scaffolds, and the scaffold microstructure has been shown to significantly influence release rates of bioactive factors. Therefore, this review attempted to investigate how the scaffold microstructure affected the release rate of bioactive factors, in which the variables included pore size, pore shape and porosity. The loading nature and the releasing mechanism of bioactive factors were also summarized. The main conclusions were achieved as follows: i) The pore shapes in the scaffold may have had no apparent effect on the release of bioactive factors but significantly affected mechanical properties of the scaffolds; ii) The pore size of about 400 µm in the scaffold may be more conducive to controlling the release of bioactive factors to promote bone formation; iii) The porosity of scaffolds may be positively correlated with the release rate, and the porosity of 70%-80% may be better to control the release rate. This review indicates that a slow-release system with proper scaffold microstructure control could be a tremendous inspiration for developing new treatment strategies for bone disease. It is anticipated to eventually be developed into clinical applications to tackle treatment-related issues effectively.

5.
ACS Appl Mater Interfaces ; 15(25): 29889-29901, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37318286

RESUMO

Bacterial infections around implants constitute a significant cause of implant failures. Early recognition of bacterial adhesion is an essential factor in preventing implant infections. Therefore, an implant capable of detecting and disinfecting initial bacterial adhesion is required. This study reports on the development of an intelligent solution for this issue. We developed an implant integrated with a biosensor electrode based on alternating current (AC) impedance technology to monitor the early growth process of Escherichia coli (E. coli) and its elimination. The biosensor electrode was fabricated by coating polypyrrole (PPy) doped with sodium p-toluenesulfonate (TSONa) on titanium (Ti) surfaces. Monitoring the change in resistance using electrochemical impedance spectroscopy (EIS), combined with an equivalent circuit model (ECM), enables the monitoring of the early adhesion of E. coli. The correlation with the classical optical density (OD) monitoring value reached 0.989. Subsequently, the eradication of bacteria on the electrode surface was achieved by applying different voltages to E. coli cultured on the electrode surface, which caused damage to E. coli. Furthermore, in vitro cellular experiments showed that the PPy coating has good biocompatibility and can promote bone differentiation.


Assuntos
Escherichia coli , Polímeros , Polímeros/farmacologia , Polímeros/química , Pirróis/química , Osso e Ossos , Bactérias , Titânio/química , Propriedades de Superfície , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química , Antibacterianos/farmacologia
6.
Discov Oncol ; 14(1): 60, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37154831

RESUMO

Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality, and a low 5-year survival rate. Exploring the potential molecular mechanisms, finding diagnostic biomarkers with high sensitivity and specificity, and determining new therapeutic targets for HCC are urgently needed. Circular RNAs (circRNAs) have been found to play a key role in the occurrence and development of HCC, while exosomes play an important role in intercellular communication; thus, the combination of circRNAs and exosomes may have inestimable potential in early diagnosis and curative therapy. Previous studies have shown that exosomes can transfer circRNAs from normal or abnormal cells to surrounding or distant cells; thereafter, circRNAs influence target cells. This review summarizes the recent progress regarding the roles of exosomal circRNAs in the diagnosis, prognosis, occurrence and development and immune checkpoint inhibitor and tyrosine kinase inhibitor resistance of HCC to provide inspiration for further research.

7.
Mol Ecol Resour ; 23(1): 294-311, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35980602

RESUMO

Critically endangered species are usually restricted to small and isolated populations. High inbreeding without gene flow among populations further aggravates their threatened condition and reduces the likelihood of their long-term survival. Chinese alligator (Alligator sinensis) is one of the most endangered crocodiles in the world and has experienced a continuous decline over the past c. 1 million years. In order to identify the genetic status of the remaining populations and aid conservation efforts, we assembled the first high-quality chromosome-level genome of Chinese alligator and explored the genomic characteristics of three extant breeding populations. Our analyses revealed the existence of at least three genetically distinct populations, comprising two breeding populations in China (Changxing and Xuancheng) and one breeding population in an American wildlife refuge. The American population does not belong to the last two populations of its native range (Xuancheng and Changxing), thus representing genetic diversity extinct in the wild and provides future opportunities for genetic rescue. Moreover, the effective population size of these three populations has been continuously declining over the past 20 ka. Consistent with this decline, the species shows extremely low genetic diversity, a large proportion of long runs of homozygous fragments, and mutational load across the genome. Finally, to provide genomic insights for future breeding management and conservation, we assessed the feasibility of mixing extant populations based on the likelihood of introducing new deleterious alleles and signatures of local adaptation. Overall, this study provides a valuable genomic resource and important genomic insights into the ecology, evolution, and conservation of critically endangered alligators.


Assuntos
Jacarés e Crocodilos , Animais , Jacarés e Crocodilos/genética , Espécies em Perigo de Extinção , Genômica , Alelos , Variação Genética
8.
Microorganisms ; 10(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36363802

RESUMO

The Chinese alligator (Alligator sinensis) is an ancient reptile with strong immunity that lives in wetland environments. This study tested the antibacterial ability of Chinese alligator serum (CAS) against Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa and analyzed the potential underlying mechanisms. Results showed that the CAS had a marked antibacterial effect on K. pneumoniae, E. coli, and P. aeruginosa, while S. aureus was only mildly affected. However, these effects disappeared when Protease K was added to the serum. The serum proteome analysis revealed that the antibacterial ability of CAS was produced by interactions among various proteins and that the complement proteins played a major antibacterial role. Therefore, we made relevant predictions about the structure and function of complement component 3. In addition, sequence alignment and phylogenetic analysis of complement component 3d (C3d) in four mammalian species and two alligator species showed that the amino acids that make up the acid pocket on the concave surface of alligator C3d are not identical to those in mammals. This study provided evidence that CAS elicits significant antibacterial effects against some pathogens and provides the basis for further development of novel antibacterial drugs.

9.
Front Microbiol ; 13: 983808, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312961

RESUMO

Nest materials are a major heat source due to rotting promoted by microbial activity. Additionally, they are a potential microbial source given their direct contact with eggshells. Microbial dynamics during incubation have been studied in wild birds; however, similar studies in reptiles remain elusive. Here, the study characterized microbial communities in the nest materials of Chinese alligator (Alligator sinensis) using high-throughput sequencing of bacterial 16S rRNA genes and fungal internal transcribed spacer (ITS) region sequences. The results showed that significant changes in the diversity and structure of microbial communities according to different incubation periods. The diversity and richness of bacterial species increased significantly over time, but the relative abundance of the most dominant bacteria in pre-incubation period, including some pathogenic bacteria, declined after incubation. In contrast, fungal species diversity and richness decreased significantly with time. Additionally, nest material composition significantly influenced microbial community structure rather than species diversity and richness. Notably, the fungal community structure showed a stronger response than bacteria to nest material composition, which varied due to differences in plant litter composition. Our results demonstrate the significant response of microbial community diversity and structure to differences in incubation periods and nest material composition in reptiles. It is further emphasized that the importance of incubation period in the conservation of the Chinese alligator and could inform similar studies in other reptiles and birds.

10.
Int J Mol Sci ; 23(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36292992

RESUMO

The gut microbiota forms a complex microecosystem in vertebrates and is affected by various factors. As a key intrinsic factor, sex has a persistent impact on the formation and development of gut microbiota. Few studies have analyzed sexual dimorphism of gut microbiota, particularly in wild animals. We used 16S rRNA gene sequencing to analyze the gut microbiota of juvenile and adult Chinese alligators, and untargeted metabolomics to study serum metabolomes of adult alligators. We observed significant sexual differences in the community diversity in juvenile, but not adult, alligators. In terms of taxonomic composition, the phylum Fusobacteriota and genus Cetobacterium were highly abundant in adult alligators, similar to those present in carnivorous fishes, whereas the gut microbiota composition in juvenile alligators resembled that in terrestrial reptiles, indicating that adults are affected by their wild aquatic environment and lack sex dimorphism in gut microbiota. The correlation analysis revealed that the gut microbiota of adults was also affected by cyanobacteria in the external environment, and this effect was sex-biased and mediated by sex hormones. Overall, this study reveals sexual differences in the gut microbiota of crocodilians and their convergence in the external environment, while also providing insights into host-microbiota interactions in wildlife.


Assuntos
Jacarés e Crocodilos , Microbioma Gastrointestinal , Animais , Caracteres Sexuais , RNA Ribossômico 16S/genética , Fator Intrínseco , Hormônios Esteroides Gonadais , China
11.
Opt Lett ; 47(11): 2899-2902, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35648959

RESUMO

Heterodyne phase-sensitive dispersion spectroscopy (HPSDS) provides an agile method for gas detection by measuring the phase of an amplitude modulation signal. However, previous HPSDS gas sensors have shown limited sensitivity. In this work, we report a new, to the best of our knowledge, dispersion spectroscopic technique, named wavelength-modulation heterodyne phase-sensitive dispersion spectroscopy (WM-HPSDS), to improve the detection sensitivity. As a proof-of-principle demonstration, a quantum cascade laser (QCL) at 5.26 µm is used to exploit the absorption line of nitric oxide (NO) in a 35-cm-long hollow-core fiber. In addition to modulating the injection current of the QCL at 1 GHz to generate the three-tone beam, a 10-kHz sinusoidal waveform is superimposed on the laser current to produce an additional wavelength modulation. We achieve a noise-equivalent concentration of 40 ppb NO using WM-HPSDS at an integration time of 90 s, corresponding to a noise-equivalent absorption (NEA) coefficient of 6.9 × 10-7 cm-1. Compared with the conventional HPSDS technique, the developed WM-HPSDS improves the sensitivity by a factor of 8.3.

12.
Front Genet ; 13: 843884, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432471

RESUMO

MicroRNA (miRNA) is a category of single-stranded non-coding small RNA (sRNA) that regulates gene expression by targeting mRNA. It plays a key role in the temperature-dependent sex determination of Chinese alligator (Alligator sinensis), a reptile whose sex is determined solely by the temperature during the incubation period and remains stable thereafter. However, the potential function of miRNAs in the gonads of adult Chinese alligators is still unclear. Here, we prepared and sequenced sRNA libraries of adult female and male alligator gonads, from breeding (in summer) and hibernating (in winter) animals. We obtained 130 conserved miRNAs and 683 novel miRNAs, which were assessed for sex bias in summer and winter; a total of 65 miRNAs that maintained sex bias in both seasons were identified. A regulatory network of sex-biased miRNAs and genes was constructed. Sex-biased miRNAs targeted multiple genes in the meiosis pathway of adult Chinese alligator oocytes and the antagonistic gonadal function maintenance pathway, such as MOS, MYT1, DMRT1, and GDF9. Our study emphasizes the function of miRNA in the epigenetic mechanisms of sex maintenance in crocodilians.

13.
Materials (Basel) ; 15(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35454591

RESUMO

The turtle carapace has a high level of protection, due to its unique biological structure, and there is great potential to use the turtle carapace structure to improve the impact resistance of composite materials using bionic theory. In this paper, the chemical elements of the turtle carapace structure, as well as its mechanical properties, were investigated by studying the composition of the compounds in each part. In addition, the bionic sandwich structure, composed of the plate, core, and backplate, was designed using modeling software based on the microstructure of the keratin scutes, spongy bone, and the spine of the turtle carapace. Additionally, finite element analysis and drop-weight experiments were utilized to validate the impact-resistant performance of the bionic structures. The numerical results show that all of the bionic structures had improved impact resistance to varying degrees when compared with the control group. The experimental results show that the split plate, the core with changing pore gradients, and the backplate with stiffener all have a considerable effect on the impact-resistance performance of overall composite structures. This preliminary study provides theoretical support for composite material optimization.

14.
Int J Gen Med ; 15: 1185-1192, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153509

RESUMO

PURPOSE: There is a limited evidence of durable effect of parathyroidectomy (PTX) on the quality of life (QoL) in dialysis populations. We aimed to investigate this concern by comparing the QoL scores in the pre- and post-PTX periods in a cohort of dialysis patients. PATIENTS AND METHODS: A total of 212 dialysis patients were enrolled in a hospital-facilitated dialysis center in China between July 1, 2016 and June 30, 2021. The mean age was 46.4 years; the male:female ratio was 96:116; hemodialysis 191, peritoneal dialysis 21. Informative data relating to demographics and dialysis were recorded for comparison. QoL was measured using the Chinese version of the Kidney Disease Quality of Life-36 (KDQOL-36™) and compared subscale scores between the pre-and post-PTX period. Appropriate statistical methods and Pearson's correlation test were used for statistical analysis. RESULTS: Nutritional markers, including hemoglobin and albumin, significantly increased post-PTX than pre-PTX. KDQOL-36 domain scale scores, including Symptoms and Problems of Kidney Disease, Burden of Kidney Disease, Effects of Kidney Disease (EKD), Physical Component Summary (PCS) score, and Mental Component Summary score, significantly increased post-PTX than pre-PTX. All patients were further stratified into three groups based on the PTX duration-0-2 years, >2-<5 years, and ≥5 years-and all KDQOL-36 domain scale scores increased in individual PTX durations. The PTX duration showed a significant negative correlation between PCS subscale scores and a positive correlation between EKD subscale scores. CONCLUSION: PTX could improve QoL in dialysis patients with medically refractory secondary hyperparathyroidism. The durable effects should be studied using a larger sample.

15.
J Clin Lab Anal ; 36(2): e24234, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35034385

RESUMO

The serum Chitinase 3-like protein 1 (CHI3L1) protein level can distinguish the stages of liver fibrosis to a great extent. However, the diagnostic and prognostic significance of serum CHI3L1 in hepatocellular carcinoma (HCC) is not clarified. To evaluate the diagnostic and prognostic value of CHI3L1 in HCC, a total of 128 HCC patients treated in the HwaMei Hospital, University of Chinese Academy of Sciences, from December 2018 to April 2020 were collected retrospectively. Matched age and gender subjects, 40 patients with liver cirrhosis, 40 patients with chronic hepatitis, and 40 healthy subjects were enrolled in the control group. The relevant clinical laboratory and examination data and the overall survival time (OS) of the HCC patients were collected. The serum CHI3L1 expression level is related to α-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, maximum tumor diameter, liver cirrhosis, and HCC patient's OS (p < 0.05). The area under the curve (AUC) of CHI3L1 was 0.7875 with the cutoff value of 91.36 ng/ml. Combining the serum CHI3L1 and α-fetoprotein (AFP) by a binary logistic regression model can increase the diagnostic sensitivity to 97.5%. Multivariate Cox regression analysis indicated that CHI3L1 is an independent prognostic factor in patients with HCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Proteína 1 Semelhante à Quitinase-3/sangue , Neoplasias Hepáticas/diagnóstico , Área Sob a Curva , Carcinoma Hepatocelular/sangue , Estudos de Casos e Controles , Feminino , Hepatite Crônica/sangue , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos
16.
Toxicol Appl Pharmacol ; 434: 115814, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843800

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) belongs to environmental endocrine disrupting chemicals (EEDCs) and can be rapidly hydrolyzed into the ultimate toxicant mono-2-ethylhexyl phthalate (MEHP). In this study, we used 5-aminofluorescein modified MEHP (MEHP-AF) as a fluorescence tracer to explore the toxicokinetics, including toxicokinetic parameters, absorption and transport across the intestinal mucosal barrier, distribution and pathological changes of organs. While the dose was as lower than 10 mg/kg by intragastric administration, the toxicokinetic parameters obtained by fluorescence microplate method were similar to those with the literatures by chromatography. MEHP-AF can be rapidly absorbed through the intestinal mucosal barrier in rats. In situ organ distribution in mice showed that MEHP-AF was mainly concentrated in the liver, kidney and testis. Our results suggested that the fluorescence tracing technique had the advantages with easy processing, less time-consuming, higher sensitivity for the quantitative determination, In addition, this technology also avoids the interference of exogenous or endogenous DEHP and MEHP in the experimental system. It also can be utilized to the visualization detection of MEHP in situ localization in the absorption organ and the toxic target organ. The results show that this may be a more feasible MEHP toxicological research method.


Assuntos
Dietilexilftalato/análogos & derivados , Fluoresceínas/química , Animais , Área Sob a Curva , Células CACO-2 , Neoplasias Colorretais , Dietilexilftalato/química , Dietilexilftalato/farmacocinética , Dietilexilftalato/toxicidade , Meia-Vida , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Imagem Óptica , Ratos , Ratos Sprague-Dawley
17.
BMC Complement Med Ther ; 21(1): 206, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372842

RESUMO

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, but there is still no effective way to stop or slow its progression. Our previous studies demonstrated that extract of Cynomorium songaricum (ECS), a Chinese herbal medicine, had neuroprotective effects in AD models in vivo. However, the pharmacological mechanism of ECS in AD is still unclear. METHODS: To study the mechanisms of action of the effects of ECS on AD, we used Aß25-35- and H2O2-exposed HT22 cells to mimic specific stages of AD in vitro. The mitochondrial membrane potential (MMP), intracellular ATP, intracellular reactive oxygen species (ROS), and expression levels of mitochondrial dynamics-related proteins in each group were examined. Furthermore, we explored the mechanisms by which ECS reduces the phosphorylation of Drp1 at Ser637 and the changes in the concentrations of intracellular calcium ions in the two models after FK506 intervention. RESULTS: The results showed that ECS significantly enhanced the MMP (P < 0.05), increased intracellular ATP levels (P < 0.05) and decreased intracellular ROS levels in the Aß- and H2O2-induced cell models (P < 0.05). Additionally, ECS regulated the expression levels of mitochondrial dynamics-related proteins by reducing the phosphorylation of Drp1 at Ser637 (P < 0.05) and decreasing the expression of Fis1 in the H2O2-induced models (P < 0.05). Further study indicated that ECS reduced the overload of intracellular calcium (P < 0.05). CONCLUSION: Our study results suggest that ECS protects the mitochondrial ultrastructure, ameliorates mitochondrial dysfunction, and maintains mitochondrial dynamics in AD models.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Cynomorium/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Humanos , Técnicas In Vitro
18.
Mater Sci Eng C Mater Biol Appl ; 124: 112039, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33947539

RESUMO

In this study, to improve the intestinal absorption of small molecule chemotherapeutic drug docetaxel (DTX) and macromolecular monoclonal antibody drug bevacizumab (BVZ), we designed and prepared a type of co-delivery nanoparticles for the oral administration of DTX and BVZ. Carboxymethyl chitosan (CMC) and poly(lactic-co-glycolic acid) (PLGA) were used as the carrier of DTX nanoparticles (CPNPDTX), and methoxy polyethylene glycol-poly (ß-amino ester) (mPEG-PAE) was used as the carrier of BVZ nanoparticles (PPNPBVZ). Then, the two nanoparticles were physically mixed in mass ratios to form mixed co-delivery nanoparticles, which was named as CPNPDTX&PPNPBVZ. The nanoparticles were characterized with pH-sensitive drug release property. CPNPDTX&PPNPBVZ could significantly increase the bioavailability of DTX and BVZ according to the more cellular uptake in Caco-2 cells and the higher absorption in the intestinal tissue. Compared with free DTX and BVZ, CPNPDTX&PPNPBVZ showed excellent cytotoxic effects on A549 cells. Our study revealed the potential of co-delivery nanoparticles of binary mixture of chemotherapeutic small molecule and macromolecular antibody drug as an oral administration therapeutic system.


Assuntos
Antineoplásicos , Nanopartículas , Administração Oral , Antineoplásicos/farmacologia , Bevacizumab/farmacologia , Células CACO-2 , Docetaxel/farmacologia , Portadores de Fármacos , Humanos , Absorção Intestinal
19.
Toxicol Appl Pharmacol ; 414: 115411, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33476678

RESUMO

Di-2-ethylhexyl phosphate (DEHP) and its main toxic metabolite mono-2-ethylhexyl phthalate (MEHP) are the typical endocrine disrupting chemicals (EDCs) and widely affect human health. Our previous research reported that synthetic nonionic dietary emulsifier polysorbate 80 (P80, E433) had the promotional effect on the oral absorption of DEHP in rats. The aim of this study was to explore its mechanism of promoting oral absorption, focusing on the mucus barrier and mucosal barrier of the small intestine. A small molecule fluorescent probe 5-aminofluorescein-MEHP (MEHP-AF) was used as a tracker of MEHP in vivo and in vitro. First of all, we verified that P80 promoted the bioavailability of MEHP-AF in the long-term and low-dose exposure of MEHP-AF with P80 as a result of increasing the intestinal absorption of MEHP-AF. Afterwards, experimental results from Western blot, qPCR, immunohistochemistry, and immunofluorescence showed that P80 decreased the expression of proteins (mucus protein mucin-2, tight junction proteins claudin-1 and occludin) related to mucus barrier and mucosal barrier in the intestine, changed the integrity of intestinal epithelial cell, and increased the permeability of intestinal epithelial mucosa. These results indicated that P80 promoted the oral absorption of MEHP-AF by altering the intestinal mucus barrier and mucosal barrier. These findings are of great importance for assessing the safety risks of some food emulsifiers and clarifying the absorption mechanism of chemical pollutants in food, especially for EDCs.


Assuntos
Dietilexilftalato/análogos & derivados , Emulsificantes/toxicidade , Células Epiteliais/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Polissorbatos/toxicidade , Animais , Disponibilidade Biológica , Células CACO-2 , Claudina-1/metabolismo , Dietilexilftalato/farmacocinética , Dietilexilftalato/toxicidade , Células Epiteliais/metabolismo , Fluoresceínas/metabolismo , Corantes Fluorescentes/metabolismo , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Masculino , Camundongos Endogâmicos ICR , Mucina-2/metabolismo , Ocludina/metabolismo , Permeabilidade , Ratos Sprague-Dawley , Distribuição Tecidual , Toxicocinética
20.
Life Sci ; 264: 118707, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33144187

RESUMO

Circular RNAs (circRNAs) are formed from the genome through diverse back splicing and feature the closed loop. circRNAs are widely available in a variety of cells and characterized by conservation, structural stability, high abundance and tissue-specific or developmental-specific expression. Recent studies have shown that circRNAs are closely related to liver diseases, such as metabolic-associated fatty liver disease, hepatitis, liver cirrhosis and hepatocellular carcinoma. circRNAs play an important role in the progression of liver diseases, are potential diagnostic and prognostic markers, and have translational value in therapy. This article reviews the research on circRNAs in liver diseases, with a view to providing a theoretical basis and new ideas for future research and treatment of liver diseases.


Assuntos
Hepatopatias/tratamento farmacológico , Hepatopatias/genética , RNA Circular/genética , Exossomos/metabolismo , Humanos , Oncogenes , RNA Circular/biossíntese , RNA Circular/metabolismo
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