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  • 1
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    Online Resource
    Neuroendocrine–Immune Regulatory Network of Eucommia ulmoides Oliver
    MDPI AG ; 2022
    In:  Molecules Vol. 27, No. 12 ( 2022-06-08), p. 3697-
    Details
    In: Molecules, MDPI AG, Vol. 27, No. 12 ( 2022-06-08), p. 3697-
    Abstract: Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine–immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules27123697
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2008644-1
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  • 2
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    Detection of Antibiotic Resistance in Feline-Origin ESBL Escherichia coli from Different Areas of China and the Resistance Elimination of Garlic Oil to Cefquinome on ESBL E. coli
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 11 ( 2023-06-01), p. 9627-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 11 ( 2023-06-01), p. 9627-
    Abstract: The development of drug-resistance in the opportunistic pathogen Escherichia coli has become a global public health concern. Due to the share of similar flora between pets and their owners, the detection of pet-origin antibiotic-resistant E. coli is necessary. This study aimed to detect the prevalence of feline-origin ESBL E. coli in China and to explore the resistance elimination effect of garlic oil to cefquinome on ESBL E. coli. Cat fecal samples were collected from animal hospitals. The E. coli isolates were separated and purified by indicator media and polymerase chain reaction (PCR). ESBL genes were detected by PCR and Sanger sequencing. The MICs were determined. The synergistic effect of garlic oil and cefquinome against ESBL E. coli was investigated by checkerboard assays, time-kill and growth curves, drug-resistance curves, PI and NPN staining, and a scanning electronic microscope. A total of 80 E. coli strains were isolated from 101 fecal samples. The rate of ESBL E. coli was 52.5% (42/80). The prevailing ESBL genotypes in China were CTX-M-1, CTX-M-14, and TEM-116. In ESBL E. coli, garlic oil increased the susceptibility to cefquinome with FICIs from 0.2 to 0.7 and enhanced the killing effect of cefquinome with membrane destruction. Resistance to cefquinome decreased with treatment of garlic oil after 15 generations. Our study indicates that ESBL E. coli has been detected in cats kept as pets. The sensitivity of ESBL E. coli to cefquinome was enhanced by garlic oil, indicating that garlic oil may be a potential antibiotic enhancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24119627
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    Thiopurine S-Methyltransferase Polymorphisms Predict Hepatotoxicity in Azathioprine-Treated Patients with Autoimmune Diseases
    MDPI AG ; 2022
    In:  Journal of Personalized Medicine Vol. 12, No. 9 ( 2022-08-28), p. 1399-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 12, No. 9 ( 2022-08-28), p. 1399-
    Abstract: Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in Azathioprine (AZA) metabolization. Although studies have discussed the association between the TPMT polymorphisms and myelosuppression, the data about the relationship between TPMT genotypes and hepatoxicity in Asian patients remain limited. This study investigated the correlation between TPMT polymorphisms and AZA-related hepatotoxicity. This study enrolled the patients who had prior exposure to AZA from the Taichung Veterans General Hospital (TCVGH)-Taiwan Precision Medicine Initiative (TPMI) cohort. Genetic variants were determined using a single nucleotide polymorphism (SNP) array. Participants were accordingly categorized into normal metabolizer (NM) and non-normal metabolizer (non-NM) groups. From the TCVGH-TPMI cohort, we included 50 TPMT non-NM patients, including 1 poor metabolizer (PM), 49 intermediate metabolizers (IMs), and 1000 NM patients. The non-NM genotype was associated with hepatotoxicity compared with the NM genotype (hazard ratio (HR): 3.85, 95% confidence interval (CI): 1.83–8.10). In the non-NM group, the 3-year cumulative incidence of hepatotoxicity was higher than that in the NM group at 8.5% in the first year and 18.6% in the second and third years (p 〈 0.001). A TPMT non-NM genotype was associated with the occurrence of hepatotoxicity following AZA therapy. Preemptive testing helps individualize AZA therapy by minimizing the risk of hepatotoxicity.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm12091399
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662248-8
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  • 4
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    Genome-Scale Investigation of GARP Family Genes Reveals Their Pivotal Roles in Nutrient Stress Resistance in Allotetraploid Rapeseed
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 22 ( 2022-11-21), p. 14484-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 22 ( 2022-11-21), p. 14484-
    Abstract: The GARP genes are plant-specific transcription factors (TFs) and play key roles in regulating plant development and abiotic stress resistance. However, few systematic analyses of GARPs have been reported in allotetraploid rapeseed (Brassica napus L.) yet. In the present study, a total of 146 BnaGARP members were identified from the rapeseed genome based on the sequence signature. The BnaGARP TFs were divided into five subfamilies: ARR, GLK, NIGT1/HRS1/HHO, KAN, and PHL subfamilies, and the members within the same subfamilies shared similar exon-intron structures and conserved motif configuration. Analyses of the Ka/Ks ratios indicated that the GARP family principally underwent purifying selection. Several cis-acting regulatory elements, essential for plant growth and diverse biotic and abiotic stresses, were identified in the promoter regions of BnaGARPs. Further, 29 putative miRNAs were identified to be targeting BnaGARPs. Differential expression of BnaGARPs under low nitrate, ammonium toxicity, limited phosphate, deficient boron, salt stress, and cadmium toxicity conditions indicated their potential involvement in diverse nutrient stress responses. Notably, BnaA9.HHO1 and BnaA1.HHO5 were simultaneously transcriptionally responsive to these nutrient stresses in both hoots and roots, which indicated that BnaA9.HHO1 and BnaA1.HHO5 might play a core role in regulating rapeseed resistance to nutrient stresses. Therefore, this study would enrich our understanding of molecular characteristics of the rapeseed GARPs and will provide valuable candidate genes for further in-depth study of the GARP-mediated nutrient stress resistance in rapeseed.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms232214484
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 5
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    2, 3, 4′, 5-tetrahydroxystilbene-2-0-β-d Glycoside Attenuates Age- and Diet-Associated Non-Alcoholic Steatohepatitis and Atherosclerosis in LDL Receptor Knockout Mice and Its Possible Mechanisms
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 20, No. 7 ( 2019-04-01), p. 1617-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 20, No. 7 ( 2019-04-01), p. 1617-
    Abstract: The compound, 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (TSG), a primary bioactive polyphenolic component of Polygonum multiflorum exerts numerous pharmacological activities. However, its protective effect against non-alcoholic steatohepatitis (NASH), in the context of metabolic syndrome, remains poorly understood. The aim of the present study is to evaluate the effects of TSG treatment on middle-aged (12-mo-old) male LDLr−/− mice, which were fed a high fat diet for 12 weeks to induce metabolic syndrome and NASH. At the end of the experiment, the blood samples of mice were collected for determination of metabolic parameters. Liver and aorta tissues were collected for analysis, such as histology, immunofluorescence, hepatic lipid content, real-time PCR, and western blot. Our data show that TSG treatment improved the different aspects of NASH (steatosis, inflammation, and fibrosis) and atherosclerosis, as well as some of the metabolic basal characteristics. These modulatory effects of TSG are mediated, at least in part, through regulating key regulators of lipid metabolism (SREBP1c, PPARα and their target genes, ABCG5 and CYP7A1), inflammation (CD68, TNF-α, IL-6 and ICAM), fibrosis (α-SMA and TNFβ) and oxidative stress (NADPH-oxidase 2/4, CYP2E1 and antioxidant enzymes). These results suggest that TSG may be a promising candidate for preventing and treating the progression of NASH.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms20071617
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
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  • 6
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    Comparisons of Anti-dsDNA Antibody Detection Methods by Chemiluminescent Immunoassay and Enzyme-Linked Immunosorbent Assay in Systemic Lupus Erythematosus
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 11 ( 2021-10-20), p. 1940-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 11 ( 2021-10-20), p. 1940-
    Abstract: This study aimed to compare the test results of anti-double-stranded DNA (anti-dsDNA) antibodies obtained using chemiluminescent immunoassay (CIA) and enzyme-linked immunosorbent assay (ELISA), and investigate predictors of inconsistent results. This retrospective study included 502 patients who underwent CIA and ELISA to determine their anti-dsDNA antibody values within a year. We compared the diagnostic power for SLE, disease activity, and predictive power for lupus nephritis (LN). A multivariate analysis was performed to determine the predictors of inconsistencies. CIA and ELISA were moderately correlated in terms of their consistency (Cronbach’s α = 0.571), and yielded comparably favorable results in terms of SLE diagnostic power and SLE disease activity. However, if the patient had LN, CIA displayed higher predictive power than ELISA (0.620 vs. 0.555, p = 0.026). Compared with the CIA/ELISA double-positive group, the inconsistent group had lower anti-C1q circulating immune complexes (CIC) antibody values (OR: 0.42, 95% CI: 0.18–0.94, p = 0.036), and lower SLEDAI scores (≥4) (OR: 0.33, 95% CI: 0.14–0.79, p = 0.013). Anti-dsDNA antibody detection with CIA exhibited higher predictability for diagnosing LN than did ELISA. In the event of inconsistencies between anti-dsDNA methods, SLE disease activity and CIC test values should be considered simultaneously.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11111940
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662336-5
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  • 7
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    Interleukin 26 Skews Macrophage Polarization Towards M1 Phenotype by Activating cJUN and the NF-κB Pathway
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 4 ( 2020-04-10), p. 938-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 4 ( 2020-04-10), p. 938-
    Abstract: Interleukin 26 (IL-26) is a new member of the IL-10 family that is highly expressed in rheumatoid arthritis (RA). However, the functions of IL-26 produced by macrophages in RA have not been elucidated. In the present work, we evaluated the effects and the mechanisms of IL-26 on M1 and M2 macrophage differentiation. Human or mouse macrophage cells were treated with lipopolysaccharides (LPS), interferon gamma (IFNγ), or IL-4 alone or concurrently treated with IL-26 to monitor M1 or M2 macrophage subtypes. The expression level of M1 or M2 macrophage genes was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The molecular mechanisms of downstream signaling activation during differentiation were investigated by immunoblotting assay. Our results found that IL-26 promoted macrophage cells from CD80+ M1 macrophage differentiation, not from the CD206+ M2 phenotype. The messenger RNA of M1-type macrophage markers tumor necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) was up-regulated in the IL-26-treated group. Also, the M1-related proinflammatory cytokines TNFα and IL-6 were induced after IL-26 stimulation. Interestingly, IL-10, a cytokine marker of M2 macrophage, was also elevated after IL-26 stimulation. Moreover, the M1-like macrophage stimulated by IL-26 underwent cJUN, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 1 (STAT1) activation. Our findings suggested the role of IL-26 in synovial macrophages of active rheumatoid arthritis and provided a new insight into IL-26 as a candidate therapeutic target in rheumatoid arthritis.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9040938
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 8
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    Therapeutic Peptide RF16 Derived from CXCL8 Inhibits MDA-MB-231 Cell Invasion and Metastasis
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 18 ( 2023-09-13), p. 14029-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 18 ( 2023-09-13), p. 14029-
    Abstract: Interleukin (IL)-8 plays a vital role in regulating inflammation and breast cancer formation by activating CXCR1/2. We previously designed an antagonist peptide, (RF16), to inhibits the activation of downstream signaling pathways by competing with IL-8 in binding to CXCR1/2, thereby inhibiting IL-8-induced chemoattractant monocyte binding. To evaluate the effect of the RF16 peptide on breast cancer progression, triple-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells were used to investigate whether RF16 can inhibit the IL-8-induced breast cancer metastasis. Using growth, proliferation, and invasiveness assays, the results revealed that RF16 reduced cell proliferation, migration, and invasiveness in MDA-MB-231 cells. The RF16 peptide also regulated the protein and mRNA expressions of epithelial–mesenchymal transition (EMT) markers in IL-8-stimulated MDA-MB-231 cells. It also inhibited downstream IL-8 signaling and the IL-8-induced inflammatory response via the mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) pathways. In the xenograft tumor mouse model, RF16 synergistically reinforces the antitumor efficacy of docetaxel by improving mouse survival and retarding tumor growth. Our results indicate that RF16 significantly inhibited IL-8-stimulated cell growth, migration, and invasion in MDA-MB-231 breast cancer cells by blocking the activation of p38 and AKT cascades. It indicated that the RF16 peptide may serve as a new supplementary drug for breast cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241814029
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Improving the Diagnostic Performance by Adding Methylation Marker to Conventional Visual Examination in Identifying Oral Cancer
    MDPI AG ; 2022
    In:  Diagnostics Vol. 12, No. 7 ( 2022-06-24), p. 1544-
    Details
    In: Diagnostics, MDPI AG, Vol. 12, No. 7 ( 2022-06-24), p. 1544-
    Abstract: Background: Visual oral examination (VOE) is a conventional oral cancer screening method. This study aimed to evaluate the value of methylation marker to assist VOE in identifying oral epithelial dysplasia and oral squamous cell carcinoma (OED/OSCC) from non-cancerous lesions in a real-world situation. Methods: 201 patients with high-risk personal habits who self-perceived oral anomaly were VOE examined, ZNF582 methylation (ZNF582m) tested, and histologically diagnosed. Results: Among them, 132 patients (65.7%) were histologically diagnosed OED/OSCC. Using VOE, 56.1% OED/OSCC patients had possible oral cancer, whereas 37.7% non-OED/OSCC patients had leukoplakia. ZNF582m-positive was detected in 90.2% OED/OSCC patients and 44.9% non-OED/OSCC patients. Various logistic regression models were postulated to evaluate the diagnostic performance of conventional VOE and new strategies using ZNF582m. ROC analysis and its corresponding C-index demonstrated that either triage or co-testing models of VOE and ZNF582m could improve diagnostic performance and discriminative abilities compared with the VOE only approach. Conclusions: In conclusion, methylation marker test shows equivalent performance to an experienced judgment by oral maxillofacial surgeons and plays a significantly supplementary role in increasing the efficacy in identifying oral malignant lesions. ZNF582m may be an especially important tool for family physicians or general dentists to properly diagnose suspicious oral lesions.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics12071544
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662336-5
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  • 10
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    Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis
    MDPI AG ; 2020
    In:  Biomedicines Vol. 8, No. 8 ( 2020-08-05), p. 275-
    Details
    In: Biomedicines, MDPI AG, Vol. 8, No. 8 ( 2020-08-05), p. 275-
    Abstract: Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines8080275
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720867-9
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