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1.
Anal Chem ; 96(2): 917-925, 2024 01 16.
Article in English | MEDLINE | ID: mdl-38171538

ABSTRACT

A high-sensitivity, low-cost, self-powered biomass electrochemical biosensor based on the "evaporating potential" theory is developed for protein detection. The feasibility of experimental evaluation methods was verified with a probe protein of bovine serum albumin. The sensor was then used to detect lung cancer marker CYFRA21-1, and the potential of our sensor for clinical diagnosis was demonstrated by serum analysis. This work innovatively exploits the osmotic power generation capability of natural wood to construct a promising electrochemical biosensor that was driven by kinetics during testing. The detection methods used for this sensor, chronoamperometry and AC impedance, showed potential for quantitative analysis and specific detection, respectively. Furthermore, the sensor could facilitate new insights into the development of high-sensitivity, low-cost, and easy-to-use electrochemical biosensors.


Subject(s)
Antigens, Neoplasm , Biosensing Techniques , Keratin-19 , Wood , Serum Albumin, Bovine , Biosensing Techniques/methods , Electrochemical Techniques/methods
2.
Sensors (Basel) ; 24(12)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38931551

ABSTRACT

A new algorithm, Yolov8n-FADS, has been proposed with the aim of improving the accuracy of miners' helmet detection algorithms in complex underground environments. By replacing the head part with Attentional Sequence Fusion (ASF) and introducing the P2 detection layer, the ASF-P2 structure is able to comprehensively extract the global and local feature information of the image, and the improvement in the backbone part is able to capture the spatially sparsely distributed features more efficiently, which improves the model's ability to perceive complex patterns. The improved detection head, SEAMHead by the SEAM module, can handle occlusion more effectively. The Focal Loss module can improve the model's ability to detect rare target categories by adjusting the weights of positive and negative samples. This study shows that compared with the original model, the improved model has 29% memory compression, a 36.7% reduction in the amount of parameters, and a 4.9% improvement in the detection accuracy, which can effectively improve the detection accuracy of underground helmet wearers, reduce the workload of underground video surveillance personnel, and improve the monitoring efficiency.

3.
Anal Chem ; 95(18): 7278-7285, 2023 05 09.
Article in English | MEDLINE | ID: mdl-37115498

ABSTRACT

Peroxynitrite (ONOO-), a kind of active nitrogen species, plays an important role in biological systems. Overproduction of ONOO- is closely related to the pathogenesis of many diseases. Therefore, it is necessary to quantify intracellular ONOO- for differentiating health and disease states. Fluorescent probes with near-infrared (NIR) fluorescence can detect ONOO- with high sensitivity and selectivity. However, there is an inevitable problem that many NIR fluorophores are easily oxidized by ONOO- to give a false-negative result. To avoid this problem, herein, we ingeniously propose a "destruction to seek to survive" strategy to detect ONOO-. Two NIR squaraine (SQ) dyes were connected together to form a fluorescent probe (SQDC). This method utilizes the destructive effect of peroxynitrite on one of the SQ moieties of SQDC to eliminate the steric hindrance, enabling the other "survived" SQ segment to enter the hydrophobic cavity of bovine serum albumin (BSA) via the well-known host-guest interactions. The encapsulation of albumin protects the "survived" SQ from further attack of ONOO-. As a result, a NIR fluorescence turn-on response coming from the host-guest interaction between BSA and the "survived" SQ escaped from SQDC was found, which can be used for the detection of ONOO-. The assembly of SQDC mixed with BSA can be located in mitochondria to detect endogenous and exogenous ONOO- sensitively in living cells. As a proof-of-concept method, it is envisioned that this novel detection strategy with a simple assembly would become a powerful means for the detection of ONOO- when employing NIR fluorophores.


Subject(s)
Cyclobutanes , Serum Albumin , Peroxynitrous Acid , Phenols/chemistry , Cyclobutanes/chemistry , Serum Albumin, Bovine/chemistry , Fluorescent Dyes/chemistry
4.
Small ; 19(35): e2301670, 2023 08.
Article in English | MEDLINE | ID: mdl-37098629

ABSTRACT

As an alternative to traditional oral and intravenous injections with limited efficacy, transdermal drug delivery (TDD) has shown great promise in tumor treatment. Over the past decade, natural polymers have been designed into various nanocarriers due to their excellent biocompatibility, biodegradability, and easy availability, providing more options for TDD. In addition, surface functionalization modification of the rich functional groups of natural polymers, which in turn are developed into targeted and stimulus-responsive functional materials, allows precise delivery of drugs to tumor sites and release of drugs in response to specific stimuli. It not only improves the treatment efficiency of tumor but also reduces the toxic and side effects to normal tissues. Therefore, the development of natural polymer-based TDD (NPTDD) systems has great potential in tumor therapy. In this review, the mechanism of NPTDD systems such as penetration enhancers, nanoparticles, microneedles, hydrogels and nanofibers prepared from hyaluronic acid, chitosan, sodium alginate, cellulose, heparin and protein, and their applications in tumor therapy are overviewed. This review also outlines the future prospects and current challenges of NPTDD systems for local treatment tumors.


Subject(s)
Drug Delivery Systems , Polymers , Administration, Cutaneous , Drug Carriers , Alginates
5.
J Dairy Sci ; 106(10): 6635-6645, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37210368

ABSTRACT

In this study, transglutaminase (TG), glucono-δ-lactone (GDL), and citric acid (CA) were used to induce the formation of whey protein isolate (WPI)-milk fat emulsion gels to embed lutein, and the emulsion gels induced in different ways were used for the preparation of processed cheese. The protective effect of emulsion gels induced in different ways on lutein was investigated, and the stability of lutein in emulsion gels and processed cheese was analyzed. The results showed that the acidification rate of CA was higher than that of GDL, which was the key step in acid-induced gels, and that the difference in acidification rate led to differences in gel structure. Compared with the 2 acid inducers (GDL and CA), TG exhibited greater potential for forming gel structures with high strength. The TG-induced emulsion gels showed the best physical stability and the highest embedding efficiency for lutein. After heat treatment (85°C), the GDL-induced emulsion gels had higher retention rate of lutein and showed good thermal stability compared with the CA-induced emulsion gels. The processed cheese added with the TG-induced emulsion gel had higher hardness and springiness compared with the processed cheese added with the other 2 kinds of emulsion gels, whereas the processed cheese added with the CA-induced emulsion gel had a lower density of network structure, showing porosity and a larger aggregated structure, but the highest bioavailability of lutein. These results provide valuable information for the formation of cold-set emulsion gel and provide the possibility for the application of emulsion gel embedding active substances in processed cheese.


Subject(s)
Cheese , Milk , Animals , Milk/chemistry , Whey Proteins/analysis , Lutein/analysis , Emulsions , Transglutaminases , Gels/chemistry
6.
J Dairy Sci ; 106(10): 6731-6740, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37210347

ABSTRACT

Brown fermented milk (BFM) is favored by consumers in the dairy market for its unique burnt flavor and brown color. However, Maillard reaction products (MRP) from high-temperature baking are also noteworthy. In this study, tea polyphenols (TP) were initially developed as potential inhibitors of MRP formation in BFM. The results showed that the flavor profile of BFM did not change after adding 0.08% (wt/wt) of TP, and its inhibition rates on 5-hydroxymethyl-2-furaldehyde (5-HMF), glyoxal (GO), methylglyoxal (MGO), Nε-carboxymethyl lysine (CML), and Nε-carboxyethyl lysine (CEL) were 60.8%, 27.12%, 23.44%, 57.7%, and 31.28%, respectively. After 21 d of storage, the levels of 5-HMF, GO, MGO, CML, and CEL in BFM with TP were 46.3%, 9.7%, 20.6%, 5.2%, and 24.7% lower than the control group, respectively. Moreover, a smaller change occurred in their color and the browning index was lower than that of the control group. The significance of this study was to develop TP as additives to inhibit the production of MRP in brown fermented yogurt without changing color and flavors, thereby making dairy products safer for consumers.


Subject(s)
Maillard Reaction , Milk , Animals , Milk/chemistry , Lysine/analysis , Polyphenols/analysis , Magnesium Oxide , Pyruvaldehyde/analysis , Glyoxal/analysis , Glycation End Products, Advanced/analysis , Tea
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(5): 598-603, 2023 May 10.
Article in Zh | MEDLINE | ID: mdl-37102297

ABSTRACT

OBJECTIVE: To analyze the clinical phenotype and genetic etiology for a child featuring congenital hypothyroidism (CH). METHODS: Whole exome sequencing (WES), copy number variation (CNV) sequencing and chromosomal microarray analysis (CMA) were carried out for a newborn infant who had presented at Linyi People's Hospital for CH. Clinical data of the child was analyzed, in addition with a literature review. RESULTS: The main characteristics of the newborn infant had included peculiar face, vulvar edema, hypotonia, psychomotor retardation, recurrent respiratory tract infection with laryngeal wheezing and feeding difficulties. Laboratory test indicated hypothyroidism. WES suggested a CNV deletion on chromosome 14q12q13. CMA further confirmed a 4.12 Mb deletion at chromosome 14q12q13.3 (32649595_36769800), which has encompassed 22 genes including NKX2-1, the pathogenic gene for CH. The same deletion was found in neither of her parents. CONCLUSION: Through the analysis of clinical phenotype and genetic variant, the child was diagnosed with 14q12q13.3 microdeletion syndrome.


Subject(s)
Congenital Hypothyroidism , Female , Humans , Congenital Hypothyroidism/genetics , DNA Copy Number Variations , Phenotype , Syndrome , Microarray Analysis
8.
Bioorg Med Chem Lett ; 75: 128973, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36075370

ABSTRACT

In the past decade, Wee1 inhibition has received widespread attention as a cancer therapy. Our research aims to discover effective, selective and drug-like Wee1 inhibitors. Herein, a series of compounds with pyrrolo[2,3-d]pyrimidine-based heterocycles were designed, synthesized and confirmed to inhibit Wee1 kinase. The inhibitors afforded good potency in Wee1 Kinase inhibitory activity in enzymatic assays. These compounds showed strong proliferation inhibition against NCI-1299 cell lines and had acceptable pharmacokinetic properties. These derivatives are promising inhibitors that warrant further evaluation, towards the development of potential anticancer drug.


Subject(s)
Antineoplastic Agents , Pyrimidines , Antineoplastic Agents/pharmacology , Cell Cycle Proteins , Cell Line, Tumor , Enzyme Inhibitors , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology
9.
Acta Pharmacol Sin ; 43(6): 1430-1440, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34654876

ABSTRACT

Transient receptor potential channel TRPV4 and nicotinamide adenine dinucleotide phosphate oxidase (Nox2) are involved in oxidative stress that increases endothelial permeability. It has been shown that obesity enhances the physical association of TRPV4 and Nox2, but the role of TRPV4-Nox2 association in obesity has not been clarified. In this study we investigated the function of TRPV4-Nox2 complex in reducing oxidative stress and regulating abnormal vascular permeability in obesity. Obesity was induced in mice by feeding a high-fat diet (HFD) for 14 weeks. The physical interaction between TRPV4 and Nox2 was measured using FRET, co-immunoprecipitation and GST pull-down assays. The functional interaction was measured by rhodamine phalloidin, CM-H2DCFDA in vitro, the fluorescent dye dihydroethidium (DHE) staining assay, and the Evans blue permeability assay in vivo. We demonstrated that TRPV4 physically and functionally associated with Nox2, and this physical association was enhanced in aorta of obese mice. Furthermore, we showed that interrupting TRPV4-Nox2 coupling by TRPV4 knockout, or by treatment with a specific Nox2 inhibitor Nox2 dstat or a specific TRPV4 inhibitor HC067046 significantly attenuated obesity-induced ROS overproduction in aortic endothelial cells, and reversed the abnormal endothelial cytoskeletal structure. In order to discover small molecules disrupting the over-coupling of TPRV4 and Nox2 in obesity, we performed molecular docking analysis and found that compound M12 modulated TRPV4-Nox2 association, reduced ROS production, and finally reversed disruption of the vascular barrier in obesity. Together, this study, for the first time, provides evidence for the TRPV4 physically interacting with Nox2. TRPV4-Nox2 complex is a potential drug target in improving oxidative stress and disruption of the vascular barrier in obesity. Compound M12 targeting TRPV4-Nox2 complex can improve vascular barrier function in obesity.


Subject(s)
Capillary Permeability , TRPV Cation Channels , Animals , Endothelial Cells/metabolism , Mice , Mice, Obese , Molecular Docking Simulation , Obesity/complications , Reactive Oxygen Species/metabolism , TRPV Cation Channels/metabolism
10.
J Dairy Sci ; 105(12): 9404-9416, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36307239

ABSTRACT

Low-fat, healthy yogurt is becoming increasingly favored by consumers. In the present study, whey protein emulsion gel microparticles were used to improve the quality of low-fat yogurt, and the effects of vegetable oil emulsion gel as a fat substitute on the qualities of low-fat yogurt were investigated, expecting to obtain healthier and even more excellent quality low-fat yogurt by applying a new method. First, emulsion gel microparticles were prepared, and then particle size distribution of emulsion gel and water holding capacity (WHC), textural properties, rheological properties, microstructure, storage stability, and sensory evaluation of yogurt were carried out. The results showed that yogurt with emulsion gel had significantly superior qualities than yogurt made with skim milk powder, with better WHC, textural properties, rheological properties, and storage stability. The average particle size of whey protein-vegetable oil emulsion gel microparticles was significantly larger than that of whey protein-milk fat emulsion gel microparticles, and the larger particle size affected the structural stability of yogurt. The WHC of yogurt made with whey protein-vegetable oil emulsion gel microparticles (V-EY) was lower (40.41%) than that of yogurt made with whey protein-milk fat emulsion gel microparticles (M-EY; 42.81%), and the texture results also showed that the hardness, consistency, and viscosity index of V-EY were inferior to these of M-EY, whereas no significant differences were found in the cohesiveness. Interestingly, the microstructure of V-EY was relatively flatter, with more and finer network branching. The whey separation between V-EY and M-EY also did not show significant differences during the 14 d of storage. Compared with yogurt made with whey protein, vegetable oil, and skim milk powder, the structure of V-EY remained relatively stable and had no cracks after 14 d of storage. The sensory evaluation results found that the total score of V-EY (62) was only lower than M-EY (65) and significantly higher than that of yogurt made with skim milk powder. The emulsion gel addition improved the sensory qualities of yogurt. Whey protein emulsion gel microparticles prepared from vegetable oil can be applied to low-fat yogurt to replace fat and improve texture and sensory defects associated with fat reduction.


Subject(s)
Milk Proteins , Yogurt , Animals , Yogurt/analysis , Whey Proteins/chemistry , Emulsions , Milk Proteins/metabolism , Powders , Plant Oils , Food Handling/methods
11.
J Exerc Sci Fit ; 20(3): 236-248, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35646130

ABSTRACT

Purpose: The definition of physical literacy (PL) needs to be explored by researchers from educational, public health, and sports organisations in Chinese culture; an adequate definition and theoretical framework of PL can then be embraced within different contexts and according to cultural influences. Methods: This meta-narrative synthesis of literature in this area included a series of planning, search, mapping, appraisal, synthesis, and recommendation phases. The literature was translated into English and circulated among international experts to seek suggestions. A total of 74 articles were included in the PL definition synthesis and 28 were included for philosophical synthesis in this study. Results: Based on three rounds of discussions, the final agreement was reached among panel members regarding the defining statements and practical and theoretical models of PL in Chinese culture. According to consensus, PL is the integration of physical, perceptual, cognitive, psychological, and behavioural capabilities, echoing with the need for an active, healthy, and fulfilling lifestyle, which involves continuous positive interactions with the environment and embodied engagement in physical activities for life. The framework addressed five domains (physical, sensory-perceptual, cognitive, psychological, and behavioural) and one important overlapping factor (dynamic environment). A further explanation was provided in the defining statement to assist in understanding the concept. Conclusion: It is suggested that the cultural interpretation and historical background of PL in Chinese discourse should be addressed and respected. The development of a specific cultural definition statement of PL in one country could provide implications for PL researchers worldwide.

12.
Wei Sheng Yan Jiu ; 51(4): 656-661, 2022 Jul.
Article in Zh | MEDLINE | ID: mdl-36047274

ABSTRACT

OBJECTIVE: To explore the risk factors of obesity in children aged 3-6 years in China. METHODS: Using search terms, preschooler, obesity, risk factors/influence factors, case-control studies, and language limited to Chinese and English, search databases(CNKI, Wanfang, VIP, CBM, PubMed, Web of science, Embase, The Cochrane library). To collect domestic and foreign literature on the case-control study design of obesity risk factors in preschool children in China published from January 1, 2000 to June 30, 2021. Stata 14.0 software was used for Meta-analysis of the included literature, and publication bias test and sensitivity analysis were performed. RESULTS: A total of 11 770 people were included in 12 papers, including 4092 in the case group and 7678 in the control group. Meta analysis shows: birth weight ≥4000 g OR=2.176, 95% CI 1.507-3.143; strong appetite OR=3.860, 95%CI 2.991-4.980; fast eating OR=2.836, 95%CI 2.552-3.152; mother overweight and obesity OR=1.903, 95%CI 1.213-2.986; mother's low level of education OR=1.744, 95%CI 1.100-2.766; Physical inactivity OR=1.488, 95%CI 1.267-1.748. CONCLUSION: Birth weight ≥ 4000 g, fast eating speed, strong appetite, mother overweight and obesity, mother's low level of education, and physical inactivity are risk factors for obesity in children aged 3-6 years.


Subject(s)
Overweight , Pediatric Obesity , Birth Weight , Case-Control Studies , Child, Preschool , China/epidemiology , Humans , Pediatric Obesity/epidemiology , Risk Factors
13.
J Cell Mol Med ; 25(17): 8115-8126, 2021 09.
Article in English | MEDLINE | ID: mdl-34346538

ABSTRACT

Previous findings have highlighted the association between oxidized high-density lipoprotein (ox-HDL) and polycystic ovary syndrome (PCOS) development; however, the underlying mechanism remains unclear. Under such context, the present study aimed to investigate the mechanism underlying the involvement of ox-HDL in PCOS in relation to the p65/micro-RNA-34a (miR-34a)/FOS axis. PCOS rat models were established with the injection of dehydroepiandrosterone (6 mg/100 g body weight). Both PCOS-modelled rats and granulosa cells (GCs) were received treatment with ox-HDL in order to identify its role in PCOS. Next, apoptosis and viability of GCs were detected with the application of TdT-mediated dUTP Nick-End Labeling and flow cytometry and Cell counting kit-8, respectively. A series of assays were performed to determine the interaction among ox-HDL, p65, miR-34a, FOS and nuclear factor-κB (NF-κB). The results revealed high expression of ox-HDL in PCOS, and enhanced endocrine disorders and ovarian damage in rats. ox-HDL promoted apoptosis of GCs and decreased its viability. ox-HDL activated NF-κB pathway and induced p65 phosphorylation to promote miR-34a expression. miR-34a targeted and inhibited FOS expression. In conclusion, our findings suggested that ox-HDL promoted the activation of p65 and transcription of miR-34a, which stimulated apoptosis of GCs and inhibited expression of FOS, resulting in the overall acceleration of PCOS development.


Subject(s)
Granulosa Cells , Lipoproteins, HDL/metabolism , MicroRNAs/metabolism , Neoplasm Proteins/metabolism , Nucleocytoplasmic Transport Proteins/metabolism , Polycystic Ovary Syndrome/metabolism , Animals , Cells, Cultured , Female , Granulosa Cells/metabolism , Granulosa Cells/pathology , Humans , Oxidation-Reduction , Primary Cell Culture , Rats , Rats, Sprague-Dawley
14.
FASEB J ; 34(10): 13573-13585, 2020 10.
Article in English | MEDLINE | ID: mdl-32803782

ABSTRACT

Cisplatin is a first-line chemotherapeutic agent for the treatment of many types of cancer, but the emergence of chemoresistance hinders its application. Thus, a better understanding of cisplatin-induced DNA damage response (DDR) would help to overcome this problem. Previously, we have identified a panel of microRNAs with altered expression after cisplatin treatment in HeLa cells. In the current study, we focused on one of them, miR-191, and investigated its function in cisplatin-induced DDR. We found that overexpression of miR-191 sensitized HeLa cells to the cytotoxic effects of cisplatin, resulted in decreased viable cells. However, overexpression of miR-191 did not cause changes in apoptotic cell ratio but rather induced significant G2/M arrest in HeLa cell treated with cisplatin. Additionally, enhanced cisplatin-induced DNA damage was observed. Through bioinformatic analysis and verified by dual-luciferase assay, it was demonstrated that the chromosome condensation 2 regulator (RCC2) gene is a target for miR-191 regulation. Furthermore, the downregulation of RCC2 by siRNA mimics the effects of miR-191, in which greater DNA damage was observed upon cisplatin treatment. Taken together, our study indicates that miR-191 may be an important player in cisplatin-induced DDR, and it elicits its function, at least partially, through the regulation of RCC2.


Subject(s)
Antineoplastic Agents/pharmacology , Chromosomal Proteins, Non-Histone/metabolism , Cisplatin/pharmacology , DNA Damage , Guanine Nucleotide Exchange Factors/metabolism , MicroRNAs/physiology , Cell Survival , Drug Resistance, Neoplasm , G2 Phase Cell Cycle Checkpoints/drug effects , HeLa Cells , Humans
15.
Mol Biol Rep ; 48(10): 6897-6909, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34453674

ABSTRACT

BACKGROUND: Environmental hypoxia affects the survival and development of organisms. It is also an important environmental factor that leads to oxidative damage. Hypoxia is a condition in which tissues are deprived of oxygen; reoxygenation is the phenomenon in which hypoxic tissues are exposed to oxygen. Hypoxia-reoxygenation is vital in pathogenesis, where the production of reactive oxygen species and antioxidant disparity significantly contribute to disease progression, and it is one of the most common physiological stressors in the aquaculture industry. METHODS AND RESULTS: In this study, the full length of complementary DNA (cDNA) of the manganese superoxide dismutase (Mn-SOD) gene of healthy cobia Rachycentron canadum was analysed using rapid amplification of cDNA ends. The real-time quantitative Polymerase Chain Reaction was used to measure the expression levels of Mn-SOD mRNAs in various tissues (heart, muscle, brain, liver, kidney, gill, intestine, and spleen). The 2-ΔΔCT method was used to performed the expression analysis. The experimental data were analysed using SPSS ver. 19.0 ( https://spss.software.informer.com/19.0/ ). P < 0.05 and P < 0.01 were set as significant differences. The values were articulated as mean ± standard deviation. The Mn-SOD gene cDNA sequence was 1209 bp long, including a 684 bp open reading frame, 42 bp 5'UTR and 483 bp 3'UTR, encoding 227 amino acids. Under hypoxia-reoxygen stress, the expression of Mn-SOD in brain tissue was significantly lower than in the control group after 8 h of reoxygenation and higher than the control group after 24 h. Hypoxia and subsequent reoxygenation triggered a disturbance in antioxidant homeostasis, displayed in the modification of GPx expression/activity in the liver: GPx was improved. CONCLUSIONS: These results provide valuable information on the role of Mn-SOD regulation in oxidative stress caused by hypoxia.


Subject(s)
Antioxidants/metabolism , Gene Expression Regulation, Enzymologic , Perciformes/genetics , Stress, Physiological , Superoxide Dismutase/genetics , Amino Acid Sequence , Animals , Base Sequence , Cell Hypoxia , Cloning, Molecular , DNA, Complementary/genetics , Gene Expression Profiling , Models, Molecular , Oxidative Stress/genetics , Phylogeny , RNA, Messenger/genetics , RNA, Messenger/metabolism , Superoxide Dismutase/chemistry
16.
Clin Lab ; 67(10)2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34655202

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is clinically characterized as a progressive cognitive impairment and behavioral disorder. Pathological hallmarks of AD include extracellular senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and massive neuronal loss. Although the exact cause of AD is not well understood, a mounting body of evidence has demonstrated that the pathogenesis of AD is associated with oxidative stress, neu-roinflammation, and amyloid beta (Aß) induced neural apoptosis. Moreover, overexpression of ß-secretase 1 (BACE1), Aß, mammalian target of rapamycin (mTOR), and Tau proteins are closely related to cognitive symptoms in AD. Studies have demonstrated that artemether, an antimalarial drug with acceptable side effects, possesses protective effects against neuroinflammation and oxidative stress. Importantly, artemether can easily penetrate the blood brain barrier, thereby representing an ideal drug candidate for AD treatment. METHODS: The effect of artemether on memory protection and the associated molecular mechanisms were investigated in an Aß25-35 induced cognitive impairments rat model. RESULTS: Results of the in vivo study showed that oral administration of artemether significantly attenuated Aß25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly downregulated the endogenous expression of Aß, BACE1, mTOR, and Tau proteins in N2a cells. CONCLUSIONS: The beneficial effect of artemether against Aß 25-35-induced cognitive impairments was attributable to the downregulation of the expression of Aß, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Amyloid Precursor Protein Secretases/genetics , Amyloid beta-Peptides , Animals , Artemether , Aspartic Acid Endopeptidases/genetics , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Peptide Fragments , Rats , TOR Serine-Threonine Kinases , tau Proteins
17.
J Sep Sci ; 44(17): 3287-3294, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34240798

ABSTRACT

Prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside are three major chromone derivatives of Saposhnikovia divaricata that have many pharmacological activities, such as anti-inflammatory and antitumor activities. In the present work, an effective method for the simultaneous separation of prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside with high purities was established using HPD-300 resin coupled with preparative high-performance liquid chromatography. The adsorption kinetics curves of the three compounds on the HPD-300 resin were studied and found to fit well according to the pseudo-second-order equation. The adsorption isotherm results indicated that the adsorption process of the three compounds was exothermic. After a one-run treatment with the resin, the contents of prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside increased from 0.29, 0.06, and 0.37% to 13.07, 2.83, and 16.91% with recovery yields of 76.38, 78.25, and 76.73%, respectively. Finally, the purities of the three compounds were found to reach more than 95% after further separation using preparative high-performance liquid chromatography. The method developed in this study was effective and could simultaneously separate three chromones from Saposhnikovia divaricate. The experimental results also showed that the HPD-300 resin is suitable for the separation of chromone derivatives.


Subject(s)
Apiaceae/chemistry , Chromones/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Monosaccharides/isolation & purification , Resins, Plant/chemistry , Xanthenes/isolation & purification , Adsorption , Chromatography, High Pressure Liquid , Chromones/chemistry , Drugs, Chinese Herbal/chemistry , Kinetics , Monosaccharides/chemistry , Particle Size , Porosity , Surface Properties , Xanthenes/chemistry
18.
World J Surg Oncol ; 19(1): 39, 2021 Feb 03.
Article in English | MEDLINE | ID: mdl-33536026

ABSTRACT

BACKGROUND: The involvement of circular RNAs (circRNAs) in tamoxifen (TAM) resistance has been identified. Herein, we aimed to identify the role and novel mechanisms of hsa_circ_0025202 in tamoxifen resistance in breast cancer (BC). METHODS: The levels of hsa_circ_0025202, microRNA (miR)-197-3p, and homeodomain-interacting protein kinase 3 (HIPK3) were tested using quantitative real-time polymerase chain reaction and western blot. IC50 value of TAM, cell proliferation, cell cycle, cell invasion, migration, apoptosis, western blot, and mouse xenograft assays was used to demonstrate the effects of hsa_circ_0025202, miR-197-3p, and HIPK3 on BC cell tumorigenesis and TAM resistance. Dual-luciferase report and RNA immunoprecipitation assays were applied to explore the potential interaction between miR-197-3p and hsa_circ_0025202 or HIPK3. RESULTS: Hsa_circ_0025202 was decreased in BC tissues and TAM resistant BC cells, and knockdown of hsa_circ_0025202 elevated the IC50 value of cells to TAM, led to the promotion of cell proliferation, invasion and migration, mediated cell cycle progression, and inhibited cell apoptosis in BC in vitro. Besides, the upregulation of hsa_circ_0025202 hindered tumor growth and promoted TAM sensitivity in vivo. In a mechanical study, hsa_circ_0025202 targeted miR-197-3p, and silencing of miR-197-3p reversed the regulatory effects of hsa_circ_0025202 knockdown on TAM resistance and malignant phenotypes. Additionally, HIPK3 was a target of miR-197-3p, and miR-197-3p overexpression enhanced TAM resistance and promoted cell malignant biological behaviors in BC by targeting HIPK3. CONCLUSION: Hsa_circ_0025202 repressed cell tumorigenesis and TAM resistance via miR-197-3p/HIPK3 axis in BC, suggesting a potential therapeutic strategy to overcome chemoresistance in BC patients.


Subject(s)
Breast Neoplasms , MicroRNAs , Animals , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Carcinogenesis/genetics , Humans , Intracellular Signaling Peptides and Proteins , Mice , MicroRNAs/genetics , Prognosis , Protein Serine-Threonine Kinases , Tamoxifen
19.
Fish Physiol Biochem ; 47(6): 1951-1967, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34633578

ABSTRACT

At present, due to the influence of global warming, seasonal change, diurnal variation, and eutrophication of the water body, hypoxia has become one of the major factors limiting the stable development of cobia (Rachycentron canadum) culture. In this study, the miRNAs involved in hypoxia stress were screened, and the target genes of miRNAs were annotated and analyzed. The results showed that a total of 184 conservative microRNA (miRNA) and 121 newly predicted miRNA were obtained by sequencing the liver of control (C) and hypoxic (dissolved oxygen, DO (2.64 ± 0.25) mg/L; 3 h) (S) groups. The pathways involved in energy metabolism included starch and sucrose metabolism (ko00500), glycosaminoglycan degradation (ko00531), and galactose metabolism (ko00052). The results indicate that the body maintains physiological activities by regulating some important pathways at the transcriptional level under hypoxia stress, such as the conversion of aerobic metabolism and anaerobic metabolism, the reduction of energy consumption, and the promotion of red blood cell proliferation to maintain the homeostasis of the body.


Subject(s)
Hypoxia , Liver/metabolism , MicroRNAs , Perciformes , Animals , Hypoxia/genetics , MicroRNAs/genetics , Perciformes/genetics
20.
Glia ; 68(9): 1757-1774, 2020 09.
Article in English | MEDLINE | ID: mdl-32057144

ABSTRACT

Olfactory ensheathing cells (OECs) are unique glial cells with axonal growth-promoting properties in the olfactory epithelium and olfactory bulb, covering the entire length of the olfactory nerve. The proliferation of OECs is necessary for the formation of the presumptive olfactory nerve layer (ONL) during development and OECs transplantation. However, the molecular mechanism underlying the regulation of OEC proliferation in the ONL still remains unknown. In the present study, we examined the role of sphingosine 1-phosphate (S1P) and S1P receptors (S1PRs) on OEC proliferation. Initially, reverse transcription-PCR (RT-PCR), western blot and immunostaining revealed that S1PRs were highly expressed in the OECs in vitro and in vivo. Furthermore, we found that S1P treatment promoted the proliferation of primary cultured OECs mediated by S1PR1. Mechanistically, yes-associated protein (YAP) was required for S1P-induced OEC proliferation through RhoA signaling. Finally, conditional knockout of YAP in OECs reduced OEC proliferation in ONL, which impaired the axonal projection and growth of olfactory sensory neurons, and olfactory functions. Taken together, these results reveal a previously unrecognized function of S1P/RhoA/YAP pathway in the proliferation of OECs, contributing to the formation of ONL and the projection, growth, and function of olfactory sensory neurons during development.


Subject(s)
Neuroglia , Olfactory Nerve , Cell Proliferation , Cells, Cultured , Lysophospholipids , Olfactory Bulb , Sphingosine/analogs & derivatives
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