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  • 1
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    Online Resource
    OAT3 Participates in Drug–Drug Interaction between Bentysrepinine and Entecavir through Interactions with M8—A Metabolite of Bentysrepinine—In Rats and Humans In Vitro
    MDPI AG ; 2023
    In:  Molecules Vol. 28, No. 4 ( 2023-02-20), p. 1995-
    Details
    In: Molecules, MDPI AG, Vol. 28, No. 4 ( 2023-02-20), p. 1995-
    Abstract: Bentysrepinine (Y101) is a novel phenylalanine dipeptide for the treatment of hepatitis B virus. Renal excretion played an important role in the elimination of Y101 and its metabolites, M8 and M9, in healthy Chinese subjects, although the molecular mechanisms of renal excretion and potential drug–drug interactions (DDIs) remain unclear. The present study aimed to determine the organic anion transporters (OATs) involved in the renal disposition of Y101 and to predict the potential DDI between Y101 and entecavir, the first-line agent against HBV and a substrate of OAT1/3. Pharmacokinetic studies and uptake assays using rat kidney slices, as well as hOAT1/3-HEK293 cells, were performed to evaluate potential DDI. The co-administration of probenecid (an inhibitor of OATs) significantly increased the plasma concentrations and area under the plasma concentration–time curves of M8 and M9 but not Y101, while reduced renal clearance and the cumulative urinary excretion of M8 were observed in rats. The time course of Y101 and M8 uptake via rat kidney slices was temperature-dependent. Moreover, the uptake of M8 was inhibited significantly by probenecid and benzylpenicillin, but not by p-aminohippurate or tetraethyl ammonium. M8 was found to be a substrate of hOAT3, but Y101 is not a substrate of either hOAT1 or hOAT3. Additionally, the entecavir inhibited the uptake of M8 in the hOAT3-transfected cells and rat kidney slices in vitro. Interestingly, no significant changes were observed in the pharmacokinetic parameters of Y101, M8 or entecavir, regardless of intravenous or oral co-administration of Y101 and entecavir in rats. In conclusion, M8 is a substrate of OAT3 in rats and humans. Furthermore, M8 also mediates the DDI between Y101 and entecavir in vitro, mediated by OAT3. We speculate that it would be safe to use Y101 with entecavir in clinical practice. Our results provide useful information with which to predict the DDIs between Y101 and other drugs that act as substrates of OAT3.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules28041995
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2008644-1
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  • 2
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    Online Resource
    Unlocking Translational Potential: Conditionally Reprogrammed Cells in Advancing Breast Cancer Research
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 19 ( 2023-09-30), p. 2388-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 19 ( 2023-09-30), p. 2388-
    Abstract: Preclinical in vitro models play an important role in studying cancer cell biology and facilitating translational research, especially in the identification of drug targets and drug discovery studies. This is particularly relevant in breast cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select patients who will be responsive to invasive or morbid therapies (radiotherapy, chemotherapy, immunotherapy, and/or surgery) are relatively lacking. To be clinically relevant, a model must accurately replicate the biology and cellular heterogeneity of the primary tumor. Addressing these requirements and overcoming the limitations of most existing cancer cell lines, which are typically derived from a single clone, we have recently developed conditional reprogramming (CR) technology. The CR technology refers to a co-culture system of primary human normal or tumor cells with irradiated murine fibroblasts in the presence of a Rho-associated kinase inhibitor to allow the primary cells to acquire stem cell properties and the ability to proliferate indefinitely in vitro without any exogenous gene or viral transfection. This innovative approach fulfills many of these needs and offers an alternative that surpasses the deficiencies associated with traditional cancer cell lines. These CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and reproduce the genomic and histological characteristics of the parental tissue. Therefore, CR technology may be a clinically relevant model to test and predict drug sensitivity, conduct gene profile analysis and xenograft research, and undertake personalized medicine. This review discusses studies that have applied CR technology to conduct breast cancer research.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12192388
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 3
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    Online Resource
    Identification and Profiling of Pituitary microRNAs of Sheep during Anestrus and Estrus Stages
    MDPI AG ; 2020
    In:  Animals Vol. 10, No. 3 ( 2020-02-29), p. 402-
    Details
    In: Animals, MDPI AG, Vol. 10, No. 3 ( 2020-02-29), p. 402-
    Abstract: MicroRNAs (miRNAs) are a class of small non-coding RNAs, molecules of 21 to 25 nucleotides in length, that regulate gene expression by binding to their target mRNA and play a significant role in animal development. The expression and role of miRNAs in regulating sheep estrus, however, remain elusive. Transcriptome analysis is helpful to understand the biological roles of miRNAs in the pituitary gland of sheep. A sheep’s pituitary gland has a significant difference between estrus and anestrus states. Here, we investigate the expression profiles of sheep anterior pituitary microRNAs (miRNAs) in two states, estrus and anestrus, using Illumina HiSeq-technology. This study identified a total of 199 miRNAs and 25 differentially expressed miRNAs in the estrus and anestrus pituitary gland in sheep. Reverse transcription quantitative-PCR (RT-qPCR) analysis shows six differentially (p 〈 0.05) expressed miRNAs, that are miR-143, miR-199a, miR-181a, miR-200a, miR-218, and miR-221 in both estrus and anestrus states. miRNAs containing estrus-related terms and pathways regulation are enriched using enrichment analysis from gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, we also envisioned a miRNA–mRNA interaction network to understand the function of miRNAs involved in the pituitary gland regulatory network. In conclusion, miRNA expression profiles in sheep pituitary gland in the anestrus and estrus deliver a theoretical basis for the study of pituitary gland biology in sheep.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani10030402
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 4
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    Online Resource
    Copper and Zinc Recovery from Sulfide Concentrate by Novel Artificial Microbial Community
    MDPI AG ; 2021
    In:  Metals Vol. 12, No. 1 ( 2021-12-25), p. 45-
    Details
    In: Metals, MDPI AG, Vol. 12, No. 1 ( 2021-12-25), p. 45-
    Abstract: Exploring efficient methods to enhance leaching efficiency is critical for bioleaching technology to deal with sulfide concentrate. In our study, a novel artificial microbial community was established to augment the bioleaching efficiency and recovery of copper (Cu) and zinc (Zn). The optimum parameters in bioleaching experiments were explored according to compare a series of conditions from gradient experiments: the pH value was 1.2, temperature was 45 °C, and rotation speed was 160 r/min, which were different with pure microorganism growth conditions. Under optimal conditions, the result of recovery for Cu and Zn indicated that the average leaching rate reached to 80% and 100% respectively, which almost increased 1.8 times and 1.2 times more than control (aseptic condition) group. Therefore, this method of Cu and Zn recovery using a new-type artificial microbial community is expected to be an environmentally-friendly and efficient bioleaching technology solution, which has the potential of large-field engineering application in the future.
    Type of Medium: Online Resource
    ISSN: 2075-4701
    URL: Article
    DOI: 10.3390/met12010045
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662252-X
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  • 5
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    Online Resource
    A Novel Prebiotic Blend Product Prevents Irritable Bowel Syndrome in Mice by Improving Gut Microbiota and Modulating Immune Response
    MDPI AG ; 2017
    In:  Nutrients Vol. 9, No. 12 ( 2017-12-09), p. 1341-
    Details
    In: Nutrients, MDPI AG, Vol. 9, No. 12 ( 2017-12-09), p. 1341-
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu9121341
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2518386-2
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  • 6
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    Polymorphism of VRTN Gene g.20311_20312ins291 Was Associated with the Number of Ribs, Carcass Diagonal Length and Cannon Bone Circumference in Suhuai Pigs
    MDPI AG ; 2020
    In:  Animals Vol. 10, No. 3 ( 2020-03-13), p. 484-
    Details
    In: Animals, MDPI AG, Vol. 10, No. 3 ( 2020-03-13), p. 484-
    Abstract: The vertnin (VRTN) gene g.20311_20312ins291 was reported as an important variant related to the number of ribs (RIB), and the ins/ins genotype was advantageous for improving RIB of Western pigs. The purpose of this study was to determine whether the VRTN gene g.20311_20312ins291 influences RIB, carcass traits, and body size traits, including cannon bone circumference (CBC) in Chinese Suhuai pigs. We found that the VRTN gene g.20311_20312ins291 was polymorphic in Suhuai fattening pigs and gilts. The polymorphism of g.20311_20312ins291 was significantly associated with RIB and CDL in Suhuai fattening pigs (p 〈 0.01), whereas this variant had no influence on carcass weight (CWT). There was a tendency of association between this variant and carcass straight length (CSL) in Suhuai fattening pigs (p = 0.06). The polymorphism of g.20311_20312ins291 was also significantly associated with CBC in Suhuai gilts (p = 0.04). Furthermore, CBC was positively genetically correlated with body length (0.22, p 〈 0.01) and body weight (0.15, p 〈 0.01). Our results indicated that the VRTN gene g.20311_20312ins291 could be used as a potential marker for improving RIB, CDL, and CBC in Suhuai pigs.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani10030484
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 7
    Online Resource
    Online Resource
    Applications of Convolutional Neural Networks to Extracting Oracle Bone Inscriptions from Three-Dimensional Models
    MDPI AG ; 2023
    In:  Symmetry Vol. 15, No. 8 ( 2023-08-12), p. 1575-
    Details
    In: Symmetry, MDPI AG, Vol. 15, No. 8 ( 2023-08-12), p. 1575-
    Abstract: In recent years, high-fidelity three-dimensional (3D) oracle bone models (3D-OBMs) have received extensive attention from oracle bone experts due to their unparalleled reducibility to real oracle bone. In the research process of 3D-OBMs, the first procedure is to extract oracle bone inscriptions (OBIs) from the model to form individual oracle bone characters (OBCs). However, the manual extraction of OBIs is a time-consuming and labor-intensive task that relies heavily on oracle bone knowledge. To address these problems, we propose a texture-mapping-based OBI extractor (tm-OBIE), which leverages the symmetrical characteristics of the texture mapping process and is able to extract 3D-OBIs from 3D-OBMs saved as a wavefront file. The OBIs in the texture file were first located using a trained 2D object detector. After that, the 3D mesh area, where the OBIs are located, was obtained using an inverse texture mapping method. Thirdly, a specific 2D plane was fitted using the centroid of triangular faces in the flat regions of the mesh via a singular value decomposition (SVD) method. Finally, by measuring the distances between the triangle meshes and the fitted plane, the meshes of the 3D-OBIs were obtained. This paper verifies the feasibility of this method via experiments and analyzes the possibility of using the algorithm framework for extracting other ancient characters from their corresponding 3D models.
    Type of Medium: Online Resource
    ISSN: 2073-8994
    URL: Article
    DOI: 10.3390/sym15081575
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518382-5
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  • 8
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    Online Resource
    A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier
    MDPI AG ; 2022
    In:  Nutrients Vol. 14, No. 10 ( 2022-05-11), p. 2010-
    Details
    In: Nutrients, MDPI AG, Vol. 14, No. 10 ( 2022-05-11), p. 2010-
    Abstract: Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu14102010
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2518386-2
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