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1.
J Cell Sci ; 137(5)2024 03 01.
Article in English | MEDLINE | ID: mdl-37818620

ABSTRACT

The membrane potential (MP) controls cell homeostasis by directing molecule transport and gene expression. How the MP is set upon epithelial differentiation is unknown. Given that tissue architecture also controls homeostasis, we investigated the relationship between basoapical polarity and resting MP in three-dimensional culture of the HMT-3522 breast cancer progression. A microelectrode technique to measure MP and input resistance reveals that the MP is raised by gap junction intercellular communication (GJIC), which directs tight-junction mediated apical polarity, and is decreased by the Na+/K+/2Cl- (NKCC, encoded by SLC12A1 and SLC12A2) co-transporter, active in multicellular structures displaying basal polarity. In the tumor counterpart, the MP is reduced. Cancer cells display diminished GJIC and do not respond to furosemide, implying loss of NKCC activity. Induced differentiation of cancer cells into basally polarized multicellular structures restores widespread GJIC and NKCC responses, but these structures display the lowest MP. The absence of apical polarity, necessary for cancer onset, in the non-neoplastic epithelium is also associated with the lowest MP under active Cl- transport. We propose that the loss of apical polarity in the breast epithelium destabilizes cellular homeostasis in part by lowering the MP.


Subject(s)
Mammary Glands, Human , Humans , Membrane Potentials , Epithelium/metabolism , Breast , Cell Communication/physiology , Cell Polarity/physiology , Epithelial Cells , Solute Carrier Family 12, Member 2/metabolism
2.
Anal Chem ; 96(18): 7304-7310, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38651947

ABSTRACT

Radicals can feature theoretically 100% light utilization owing to their nonelectron spin-forbidden transition and represent the most advanced luminescent materials at present. 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO) acts as a typically stable radical with very broad applications. However, their luminescent properties have not been discovered to date. In the present work, we observed the bright electrochemiluminescence (ECL) emission of TEMPO with a higher efficiency (72.3%) via the electrochemistry and coreactant strategies for the first time. Moreover, the radical-based ECL achieved high detection toward boron acid with a lower limit of detection (LOD) of 1.9 nM. This study offers a new approach to generate emissions for some unconventional luminophores and makes a major breakthrough in the field of new luminescent materials as well.

3.
Mol Pharm ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951109

ABSTRACT

The poor delivery efficiency of nanotherapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. An active targeting system with high efficiency and few side effects is a promising strategy for tumor therapy. Herein, a multifunctional nanomedicine Nb2C-PAA-DOX@Apt-M (NDA-M) was constructed for targeted photothermal/chemotherapy (PTT/CHT) combined tumor therapy. The specific targeting ability of aptamer could effectively enhance the absorption of nanomedicine by the MCF-7 cell. By employing Apt-M, the NDA-M nanosheets demonstrated targeted delivery to MCF-7 cells, resulting in enhanced intracellular drug concentration. Under 1060 nm laser irradiation, a rapid temperature increase of the NDA-M was observed within the tumor region to achieve PTT. Meanwhile, CHT was triggered when DOX release was induced by photothermal/acid stimulation. The experimental results demonstrated that aptamer-mediated targeting achieved enhanced PTT/CHT efficacy both in vitro and in vivo. Notably, NDA-M induced complete ablation of solid tumors without any adverse side effects in mice. This study demonstrated new and promising tactics for the development of nanomaterials for targeted tumor therapy.

4.
Article in English | MEDLINE | ID: mdl-38430181

ABSTRACT

Objective: Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs in 3-5% of pregnancies. The inflammatory response is essential to the development of GDM. Resistant dextrin is a natural fiber and exhibits an antidiabetic effect against diabetes. We investigate resistant dextrin's preventive role and underlying mechanism against STZ-induced GDM. Material and method: Female Wistar rats were utilized, and GDM was induced in pregnant rats using STZ. The levels of glycated hemoglobin (HbA1c), resistin, serum-c-peptide, free fatty acid, antioxidant, hepatic glycogen, lipid, inflammatory cytokines, apoptosis, and inflammatory parameters were estimated. mRNA expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) was estimated. We also estimated the histopathology of pancreatic and liver tissue. Result: Body weight, plasma insulin, fetal body weight, and blood glucose levels were all considerably (P < .001) improved by resistant dextrin, while placental weight and blood sugar levels were also decreased. Resistant dextrin significantly (P < .001) suppressed the levels of HbA1c, resistin, serum-c-peptide, and hepatic glycogen and improved the free fatty acid (FFA) level. Resistant dextrin significantly (P < .001) altered the level of adiponectin, leptin, intercellular Adhesion Molecule 1 (ICAM-1), and visfatin; antioxidant parameters such as malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase GST, inflammatory cytokines like tumor necrosis factor- α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-2 (IL-2), interferon- γ (INF-γ), interleukin-10 (IL-10); apoptosis parameters include Bcl-2, caspase-3, and Bax, respectively. Resistant dextrin significantly (P < .001) suppressed the mRNA expression of NF-κB, MyD88, NLRP3, and TLR4. Resistant dextrin altered the histopathological changes in the pancreas and hepatic tissue. Discussion and Conclusion: In short, resistant dextrin demonstrated a protective effect against STZ-induced GDM by modulating the TLR4/MyD88/NF-κB signaling pathway.

5.
Cytokine ; 165: 156161, 2023 05.
Article in English | MEDLINE | ID: mdl-36921509

ABSTRACT

Fibrosis refers to the phenomenon that fibrous connective tissues are increased and parenchymal cells are decreased in organs or tissues such as lung, heart, liver, kidney, skin and so on. It usually occurs at the late stage of repair of chronic or recurrent tissue damage. Fibrotic disease is the main factor for the morbidity and mortality of all tissues and organ systems. Long-term fibrosis can lead to organ and tissue dysfunction and even failure. Interleukin -1 family cytokines are a series of classical inflammatory factors and involved in the occurrence and development process of multiple fibrotic diseases, its biological function, relationship with diseases and application are more and more favored by scientists from various countries. So far, 11 cytokines and 10 receptors of IL-1 family have been identified. In this paper, the cytokines, receptors, signaling pathways and biological functions of IL-1 family are summarized, and the correlation with fibrosis diseases is analyzed.


Subject(s)
Cytokines , Interleukin-1 , Humans , Interleukin-1/metabolism , Fibrosis , Cytokines/metabolism , Liver/metabolism , Lung/metabolism
6.
Sensors (Basel) ; 24(1)2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38202883

ABSTRACT

A robot screwing skill learning framework based on teaching-learning is proposed to improve the generalization ability of robots for different scenarios and objects, combined with the experience of a human operation. This framework includes task-based teaching, learning, and summarization. We teach a robot to twist and gather the operation's trajectories, define the obstacles with potential functions, and counter the twisting of the robot using a skill-learning-based dynamic movement primitive (DMP) and Gaussian mixture model-Gaussian mixture regression (GMM-GMR). The hole-finding and screwing stages of the process are modeled. In order to verify the effectiveness of the robot tightening skill learning model and its adaptability to different tightening scenarios, obstacle avoidance trends and tightening experiments were conducted. Obstacle avoidance and tightening experiments were conducted on the robot tightening platform for bolts, plastic bottle caps, and faucets. The robot successfully avoided obstacles and completed the twisting task, verifying the effectiveness of the robot tightening skill learning model and its adaptability to different tightening scenarios.

7.
Int Wound J ; 20(2): 381-390, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35906851

ABSTRACT

Pressure injury is a serious and preventable problem in intensive care units. Translating guidelines into clinical practice can reduce the incidence of pressure injury. Identifying clinical status, barriers and facilitators contribute to guideline implementation. To identify the knowledge, attitudes, and practices of pressure injury prevention in Chinese critical care nurses. Secondary data were extracted from a multicentric clinical trial. Knowledge and attitudes toward pressure injury prevention were assessed by a fourteen-item questionnaire. The observed practices were recorded using a case report form. The report complies with the STROBE statement. A total of 950 critical care nurses in 15 hospitals from six provinces of China were investigated. A total of 53.1% of nurses received a median score of 6 points or less. Knowledge regarding the repositioning procedure, risk assessment, and heel pressure injury prevention was insufficient. Over 99% of nurses strongly or somewhat agreed that pressure injury prevention was very important and that they were willing to take measures to prevent pressure injury. A total of 27 781 patient days of pressure injury prevention practice were recorded. Repositioning was the most commonly used prevention measure, followed by support surfaces and prophylactic dressings. A combination of repositioning, support surface, and prophylactic dressing was lacking. Chinese critical nurses showed a low level of knowledge and a positive attitude toward pressure injury prevention. Practices of pressure injury prevention were unsatisfactory. There is a clear gap between the guidelines and clinical practices. The barrier (low-level knowledge) and facilitator (positive attitude) were identified in this study. According to these findings, strategies need to be developed to promote guideline implementation.


Subject(s)
Nurses , Pressure Ulcer , Humans , Cross-Sectional Studies , Clinical Competence , Health Knowledge, Attitudes, Practice , Pressure Ulcer/prevention & control , Critical Care , China , Surveys and Questionnaires
8.
BMC Geriatr ; 22(1): 702, 2022 08 24.
Article in English | MEDLINE | ID: mdl-35999509

ABSTRACT

BACKGROUND: Some studies associate frailty and postoperative mortality in hip or knee replacement patients, and others have explored the relationship between the frailty index and changes in postoperative mortality in hip or knee replacement patients, but their findings are not consistent. This meta-analysis and systematic review aimed to pool the results of existing studies to explore whether frailty is an independent risk factor for postoperative mortality in patients with lower limb arthroplasty (including hip or knee arthroplasty). METHODS: On December 15, 2021, we searched the relevant articles from the PubMed, Embase, Medline (via Ovid), China National Knowledge Infrastructure (CNKI) and Wan Fang Med Online databases. We used the Newcastle-Ottawa Scale (NOS) to assess the quality of the articles that met the exclusion and inclusion criteria. R Studio was used to analyze the effect sizes (based on the random model integration) on the extracted data. Meanwhile, potential publication bias and sensibility analysis were performed. RESULTS: We included seven studies, which included a total of 460,594 patients, for quantitative analysis. Overall, frailty increased the risk of mortality in lower limb arthroplasty patients compared to those without frailty, as measured by a pooled risk ratio (RR) of 2.46 (95% confidence interval [CI]: 1.81-3.33). Additionally, subgroup analysis based on population revealed that the pooled RRs for total knee arthroplasty (TKA) patients in three studies and total hip arthroplasty (THA) patients in four studies were 2.61 (95% CI: 2.26-3.02) and 3.18 (95% CI: 1.92-5.28), respectively, for TKA patients in three studies and THA patients in four studies. Additionally, these statistically significant positive associations persisted in subgroup analyses by study design, geographic region, and follow-up period. CONCLUSION: Frailty is an independent risk factor for postoperative mortality in patients undergoing lower limb arthroplasty, according to our findings. This suggests that frailty may be a predictor of preoperative risk stratification for patients with such elective surgery and could alert doctors and nurses of early screening and medical care interventions in patients with such a need for surgery to reduce postoperative mortality in lower limb arthroplasty patients.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Frailty , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Frailty/diagnosis , Humans , Lower Extremity , Odds Ratio
9.
Analyst ; 146(4): 1340-1345, 2021 Feb 22.
Article in English | MEDLINE | ID: mdl-33367331

ABSTRACT

Prostate specific antigen (PSA) has been considered as the most potential serological biomarker for the early stage detection of prostate cancer. Here, a label-free fluorescence aptasensing strategy for detecting PSA based on hybridization chain reaction (HCR) and G-quadruplex DNAzymes has been developed. This designed strategy consists of three DNA probes, aptamer probe (AP), hairpin probe 1 (H1) and hairpin probe 2 (H2). In the presence of target PSA, the aptamer sequences in AP specifically recognized PSA to form a PSA-aptamer complex, causing an AP conformation change and thus releasing the initiator, which triggered the chain-like assembly of H1 and H2 that yielded extended nicked double-stranded DNA through HCR. Upon the addition of hemin, the G-rich segments at the end of H1 and H2 self-assembled into the peroxidase-mimicking hemin/G-quadruplex DNAzymes, which catalyzed the hydrogen peroxide-mediated oxidation of thiamine to give a fluorescence signal dependent on the concentration of PSA. Under optimal conditions, a limit of detection of 0.05 nM and a linear range from 0.1 nM to 1 nM (R2 = 0.9942) were achieved by this assay. In addition, other interfering proteins, such as IgG, AFP and CEA, did not produce any significant change in the fluorescence intensity response, indicating good selectivity of this sensor for PSA detection. Finally, this proposed aptasensor was successfully used for diluted serum samples.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , DNA, Catalytic , G-Quadruplexes , Humans , Limit of Detection , Male , Prostate-Specific Antigen
10.
Bioorg Med Chem ; 45: 116329, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34329818

ABSTRACT

Agrimonia pilosa (AP), Galla rhois (RG), and their mixture (APRG64) strongly inhibited SARS-CoV-2 by interfering with multiple steps of the viral life cycle including viral entry and replication. Furthermore, among 12 components identified in APRG64, three displayed strong antiviral activity, ursolic acid (1), quercetin (7), and 1,2,3,4,6-penta-O-galloyl-ß-d-glucose (12). Molecular docking analysis showed these components to bind potently to the spike receptor-binding-domain (RBD) of the SARS-CoV-2 and its variant B.1.1.7. Taken together, these findings indicate APRG64 as a potent drug candidate to treat SARS-CoV-2 and its variants.


Subject(s)
Agrimonia/chemistry , Antiviral Agents/chemistry , Biological Products/chemistry , COVID-19 Drug Treatment , Plant Extracts/chemistry , SARS-CoV-2/drug effects , Amino Acid Sequence , Antiviral Agents/pharmacology , Biological Products/pharmacology , Drug Discovery , Humans , Hydrolyzable Tannins/chemistry , Molecular Docking Simulation , Plant Extracts/pharmacology , Protein Binding , Quercetin/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Triterpenes/chemistry , Virus Internalization/drug effects , Ursolic Acid
11.
J Biol Chem ; 294(25): 9911-9923, 2019 06 21.
Article in English | MEDLINE | ID: mdl-31085587

ABSTRACT

Enzalutamide, approved by the United States Food and Drug Administration in 2018 for the management of metastatic castration-resistant prostate cancer (CRPC), is an androgen receptor (AR) inhibitor. It blocks androgen binding to the AR, AR nuclear translocation, and AR-mediated DNA binding. Unfortunately, a considerable proportion of tumors eventually develop resistance during the treatment. The molecular mechanisms underlying enzalutamide resistance are not completely understood. Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressor complex 2, has been proposed as a prognostic marker for prostate cancer (PCa). With the goal to test whether EZH2 also plays a critical role in acquisition of enzalutamide resistance in CRPC, here we examined whether EZH2 inhibition/depletion enhances the efficacy of enzalutamide in enzalutamide-resistant PCa cells. We show that combining the EZH2 inhibitor GSK126 with enzalutamide synergistically inhibits cell proliferation and colony formation and promotes apoptosis in enzalutamide-resistant PCa cells. EZH2 depletion also overcomes enzalutamide resistance in both cultured cells and xenograft tumors. Mechanistically, we found that EZH2 directly binds to the promoter of prostate-specific antigen and inhibits its expression in enzalutamide-resistant PCa cells. In agreement, bioinformatics analysis of clinical RNA sequencing data involving GSEA indicated a strong correlation between AR and EZH2 gene expression during PCa progression. Our study provides critical insights into the mechanisms underlying enzalutamide resistance, which may offer new approaches to enhance the efficacy of enzalutamide in CRPC.


Subject(s)
Drug Resistance, Neoplasm , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , Gene Expression Regulation, Neoplastic/drug effects , Phenylthiohydantoin/analogs & derivatives , Prostatic Neoplasms, Castration-Resistant/drug therapy , Receptors, Androgen/chemistry , Animals , Apoptosis , Benzamides , Cell Proliferation , Enhancer of Zeste Homolog 2 Protein/genetics , Enhancer of Zeste Homolog 2 Protein/metabolism , Humans , Male , Mice , Mice, Nude , Nitriles , Phenylthiohydantoin/pharmacology , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Signal Transduction , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
12.
Prostate ; 80(3): 256-266, 2020 02.
Article in English | MEDLINE | ID: mdl-31856338

ABSTRACT

BACKGROUND: Because androgen receptor (AR) signaling is essential for prostate cancer (PCa) initiation and progression, castration is the main approach for treatment. Unfortunately, patients tend to enter a stage called castration-resistant prostate cancer (CRPC) despite the initial response to castration. For various reasons, AR signaling is reactivated in CRPC. As such, AR signaling inhibitors, such as enzalutamide, has been approved by the Food and Drug Administration to treat CRPC in the clinic. However, the limited success of these new drugs suggests an immediate unmet need to understand the underlying mechanisms for resistance so novel targets can be identified to enhance their efficacy. METHODS: An unbiased bioinformatics analysis was performed with the existing human patient dataset and RNA-seq results of in-house PCa cell lines to identify new targets to overcome enzalutamide resistance. Cell viability and growth were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and colony formation assay. Cell invasion and migration were detected by transwell assay. Protein levels were detected by Western blot or immunofluorescence. RESULTS: We found that the noncanonical Wnt signaling was activated in enzalutamide-resistant PCa cells and that the activation of noncanonical Wnt signaling was correlated with AR expression and disease progression. This was validated by the elevated expression of noncanonical Wnt pathway members such as Wnt5a, RhoA, and ROCK in enzalutamide-resistant PCa cells in comparison to their enzalutamide-sensitive counterparts. And, both Y27632, an inhibitor of ROCK, and depletion of ROCK enhanced the efficacy of enzalutamide in enzalutamide-resistant PCa cells. Of significance, a combination of Y27632 and enzalutamide inhibited 22RV1-derived xenograft tumor growth synergistically. Finally, ROCK depletion plus enzalutamide treatment inhibited invasion and migration of enzalutamide-resistant PCa cells via inhibition of epithelial-mesenchymal transition. CONCLUSIONS: The noncanonical Wnt pathway is activated in enzalutamide-resistant PCa and inhibition of noncanonical Wnt pathway overcomes enzalutamide resistance and enhances its efficacy in CRPC.


Subject(s)
Amides/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Phenylthiohydantoin/analogs & derivatives , Prostatic Neoplasms, Castration-Resistant/drug therapy , Pyridines/pharmacology , Wnt Signaling Pathway/drug effects , Amides/administration & dosage , Animals , Benzamides , Cell Line, Tumor , Cell Movement/drug effects , Drug Resistance, Neoplasm , Drug Synergism , Humans , Male , Mice , Nitriles , Phenylthiohydantoin/administration & dosage , Phenylthiohydantoin/pharmacology , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Pyridines/administration & dosage , Random Allocation , Receptors, Androgen/metabolism , Xenograft Model Antitumor Assays , rho-Associated Kinases/antagonists & inhibitors , rho-Associated Kinases/metabolism
13.
J Biol Chem ; 293(37): 14328-14341, 2018 09 14.
Article in English | MEDLINE | ID: mdl-30089652

ABSTRACT

Enzalutamide, a nonsteroidal second-generation antiandrogen, has been recently approved for the management of castration-resistant prostate cancer (CRPC). Although patients can benefit from enzalutamide at the beginning of this therapy, acquired enzalutamide resistance usually occurs within a short period. This motivated us to investigate the mechanism involved and possible approaches for overcoming enzalutamide resistance in CRPC. In the present study, we found that 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), a crucial enzyme in the mevalonate pathway for sterol biosynthesis, is elevated in enzalutamide-resistant prostate cancer cell lines. HMGCR knockdown could resensitize these cells to the drug, and HMGCR overexpression conferred resistance to it, suggesting that aberrant HMGCR expression is an important enzalutamide-resistance mechanism in prostate cancer cells. Furthermore, enzalutamide-resistant prostate cancer cells were more sensitive to statins, which are HMGCR inhibitors. Of note, a combination of simvastatin and enzalutamide significantly inhibited the growth of enzalutamide-resistant prostate cancer cells in vitro and tumors in vivo Mechanistically, simvastatin decreased protein levels of the androgen receptor (AR), which was further reduced in combination with enzalutamide. We observed that the decrease in AR may occur through simvastatin-mediated inhibition of the mTOR pathway, whose activation was associated with increased HMGCR and AR expression. These results indicate that simvastatin enhances the efficacy of enzalutamide-based therapy, highlighting the therapeutic potential of statins to overcome enzalutamide resistance in CRPC.


Subject(s)
Cholesterol/biosynthesis , Drug Resistance, Neoplasm , Phenylthiohydantoin/analogs & derivatives , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/metabolism , Animals , Benzamides , Cell Line, Tumor , Humans , Hydroxymethylglutaryl CoA Reductases/genetics , Hydroxymethylglutaryl CoA Reductases/metabolism , Male , Mice , Mice, Nude , Nitriles , Phenylthiohydantoin/administration & dosage , Prostatic Neoplasms, Castration-Resistant/enzymology , Prostatic Neoplasms, Castration-Resistant/genetics , Receptors, Androgen/genetics , Receptors, Androgen/metabolism
14.
Microb Pathog ; 131: 81-86, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30910720

ABSTRACT

This study aimed to investigate the mechanism of lipopolysaccharide (LPS) released in the rumen on epithelium barrier function of goats fed a HC diet. Twelve Boer goats were randomly divided into two groups: low-concentrate(LC) diet and high-concentrate(HC) diet treatment. We found that the pH of rumen fluid in the HC group was lower than in the LC group (P < 0.05). The mRNA and protein expression levels of p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK) in the rumen epithelium were lower in the LC group than the HC group (P < 0.05). Gene expression and protein levels of the tight junction proteins claudin-1, claudin-4, occludin, and Zona occludin-1 were all greater in the LC group than the HC group (P < 0.05). Staining of claudin-1, occludin and ZO-1 was became irregular. In conclusion, high concentrate diet feeding can impair rumen epithelium function and decrease tight junction protein expression through MAPK signaling pathway.


Subject(s)
Diet/veterinary , Epithelium/metabolism , Lipopolysaccharides/metabolism , Rumen/metabolism , Animal Feed/analysis , Animals , Claudin-1/genetics , Claudin-1/metabolism , Claudin-4/genetics , Claudin-4/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression Regulation , Goats , Hydrogen-Ion Concentration , JNK Mitogen-Activated Protein Kinases/metabolism , Occludin/genetics , Occludin/metabolism , Random Allocation , Signal Transduction , Tight Junction Proteins/genetics , Tight Junction Proteins/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
16.
Bioorg Chem ; 93: 103320, 2019 12.
Article in English | MEDLINE | ID: mdl-31585267

ABSTRACT

Hepatitis C virus (HCV) infection is a significant health problem, with a worldwide prevalence of about 170 million. Recently, the development of direct acting antiviral (DAA) as a therapeutic agent for HCV has been rapidly increasing. However, DAA has a side effect and is costly. Therefore, it is still necessary to develop a therapeutic agent to treat HCV infection using products. Agrimonia pilosa (AP) and Galla rhois (RG) are traditional medicines and are known to display therapeutic activity on various diseases. Notably, they have been reported to have an anti-viral effect on HBV and influenza virus infections. It is expected that anti-viral activity will increase when two extracts are mixed. To investigate their anti-viral activity, the expression level of HCV Core 1b and NS5A was measured. Remarkably, AP, RG, and their mixed compound (APRG64) strongly inhibited the expression of viral proteins, which led us to identify their metabolites. A total of 14 metabolites were identified using liquid chromatography mass spectrometry (LC-MS). These metabolites were evaluated for their anti-HCV activity to identify active ingredients. In conclusion, our results unveiled that anti-HCV activity of Agrimonia pilosa and Galla rhois extract mixture could lead to the development of a novel therapy for HCV infection.


Subject(s)
Agrimonia/chemistry , Antiviral Agents/pharmacology , Biological Products/chemistry , Hepacivirus/drug effects , Plant Extracts/pharmacology , Cell Line , Chromatography, High Pressure Liquid/methods , Humans , Mass Spectrometry/methods , Microbial Sensitivity Tests
17.
Nucleic Acids Res ; 45(20): 11725-11742, 2017 Nov 16.
Article in English | MEDLINE | ID: mdl-28981686

ABSTRACT

The nuclear mitotic apparatus protein, NuMA, is involved in major cellular events such as DNA damage response, apoptosis and p53-mediated growth-arrest, all of which are under the control of the nucleolus upon stress. Proteomic investigation has identified NuMA among hundreds of nucleolar proteins. Yet, the precise link between NuMA and nucleolar function remains undetermined. We confirm that NuMA is present in the nucleolus and reveal redistribution of NuMA upon actinomycin D or doxorubicin-induced nucleolar stress. NuMA coimmunoprecipitates with RNA polymerase I, with ribosomal proteins RPL26 and RPL24, and with components of B-WICH, an ATP-dependent chromatin remodeling complex associated with rDNA transcription. NuMA also binds to 18S and 28S rRNAs and localizes to rDNA promoter regions. Downregulation of NuMA expression triggers nucleolar stress, as shown by decreased nascent pre-rRNA synthesis, fibrillarin perinucleolar cap formation and upregulation of p27kip1, but not p53. Physiologically relevant nucleolar stress induction with reactive oxygen species reaffirms a p53-independent p27kip1 response pathway and leads to nascent pre-rRNA reduction. It also promotes the decrease in the amount of NuMA. This previously uncharacterized function of NuMA in rDNA transcription and p53-independent nucleolar stress response supports a central role for this nuclear structural protein in cellular homeostasis.


Subject(s)
Antigens, Nuclear/genetics , Cell Nucleolus/genetics , DNA, Ribosomal/genetics , Nuclear Matrix-Associated Proteins/genetics , Transcription, Genetic , Antigens, Nuclear/metabolism , Blotting, Western , Cell Cycle Proteins , Cell Line , Cell Line, Tumor , Cell Nucleolus/drug effects , Cell Nucleolus/ultrastructure , Chromosomal Proteins, Non-Histone/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Dactinomycin/pharmacology , Doxorubicin/pharmacology , Humans , Microscopy, Electron , Nuclear Matrix-Associated Proteins/metabolism , Protein Binding , RNA Interference , RNA Polymerase I/metabolism , RNA, Ribosomal/metabolism , Ribosomal Proteins/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
18.
Sensors (Basel) ; 19(3)2019 Feb 07.
Article in English | MEDLINE | ID: mdl-30736400

ABSTRACT

A novel colorimetric and ratiometric fluorescence sensor was constructed by using carbon quantum dots (CQDs) and o-diaminobenzene (ODB). Unlike ODB by itself, ODB oxide (oxODB) not only emits fluorescence, but also produces ultraviolet (UV) absorption. Therefore, on the basis of the potential optical properties of ODB, glucose oxidase (Gox) and horseradish peroxidase (HRP) were introduced into a CQDs⁻ODB system for the quantitative oxidation of ODB. When glucose is present, it is oxidized by oxygen under the catalytic action of its oxidase to form hydrogen peroxide. Hydrogen peroxide is a strong oxidant that can rapidly oxidize ODB through the catalysis of horseradish peroxidase. oxODB can cause changes in the fluorescence ratio (I550/I446) and absorbance ratio (A/A0). At the same time, the color of the detection solution can also change under sunlight and ultraviolet lamps. Therefore, glucose can be quantitatively detected by ratiometric fluorescence and colorimetry simultaneously, and semi-quantitatively detected by observing the colors with sunlight and ultraviolet lamps of 365 nm. This increases not only the convenience but also the accuracy of detection. In addition, this sensor has good selectivity and can be used for the determination of glucose in serum, providing a new idea for the development of blood glucose sensors.

19.
Asian-Australas J Anim Sci ; 32(6): 783-791, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30477292

ABSTRACT

OBJECTIVE: This study was to evaluate the fermentation dynamics, structural and nonstructural carbohydrate composition and in vitro gas production of rice straw ensiled with lactic acid bacteria and molasses. METHODS: Fresh rice straw was ensiled in 1-L laboratory silos with no additive control (C), Lactobacillus plantarum (L), molasses (M) and molasses+Lactobacillus plantarum (ML) for 6, 15, 30, and 60 days. After storage, the silages were subjected to microbial and chemical analyses as well as the further in vitro fermentation trial. RESULTS: All additives increased lactic acid concentration, and reduced pH, dry matter (DM) loss and structural carbohydrate content relative to the control (p<0.05). The highest organic acid and residual sugar contents and lignocellulose reduction were observed in ML silage. L silage had the highest V-score with 88.10 followed by ML silage. L and ML silage improved in vitro DM digestibility as compared with other treatments, while in vitro neutral detergent fibre degradability (IVNDFD) was increased in M and ML silage (p<0.05). M silage significantly (p<0.05) increased propionic acid (PA) content and decreased butyric acid content and acetic acid/PA as well as 72-h cumulative gas production. CONCLUSION: The application of ML was effective for improving both the fermentation quality and in vitro digestibility of rice straw silage. Inclusion with molasses to rice straw could reduce in vitro ruminal gas production.

20.
BMC Vet Res ; 14(1): 376, 2018 Dec 03.
Article in English | MEDLINE | ID: mdl-30509252

ABSTRACT

BACKGROUND: The effect of soybean hull feeding on the disruption of colonic epithelium barrier function was investigated in goats fed a high-concentrate diet. Twenty-one Boer goats (live weight, 32.57 ± 2.26 kg; age, 1 year) were randomly divided into three groups: low-concentrate diet (LC), high-concentrate diet (HC), and high-concentrate diet with soybean hulls (SH). RESULTS: We found that the rumen fluid in the LC and SH group shown a higher pH value compared with the HC group. The mRNA and protein expression levels of extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in the colonic epithelium were significantly decreased in the SH group than in the HC group. Moreover, in goats fed the HC diet, SH treatment promoted gene expression and protein abundance of claudin-1, claudin-4, occludin, and ZO-1 in the colonic epithelium. Additionally, the injury to the colonic epithelium barrier caused by the HC diet was reversed by SH treatment. CONCLUSIONS: Our results indicated that supplemental SH feeding reverses the damage to colonic epithelium tight junctions by inhibiting the MAPK signalling pathway and has a protective effect on the colonic epithelium during SARA.


Subject(s)
Colon/metabolism , Diet/veterinary , Gene Expression Regulation , Glycine max , Goats/physiology , Intestinal Mucosa/metabolism , Animal Feed/standards , Animals , Gastrointestinal Contents/chemistry , Gene Expression Profiling/veterinary , Goats/metabolism , Hydrogen-Ion Concentration , Protein Kinases/genetics , Random Allocation
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