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  • 1
    Online Resource
    Online Resource
    Inhibition of PARP Potentiates Immune Checkpoint Therapy through miR-513/PD-L1 Pathway in Hepatocellular Carcinoma
    Hindawi Limited ; 2022
    In:  Journal of Oncology Vol. 2022 ( 2022-4-13), p. 1-16
    Details
    In: Journal of Oncology, Hindawi Limited, Vol. 2022 ( 2022-4-13), p. 1-16
    Abstract: Background. The DNA repair enzyme poly(ADP-ribose) polymerase (PARP) is involved in DNA damage repair and cell death. However, the association between PARP’s biological activities and the immune microenvironment in hepatocellular carcinoma (HCC) is unclear. The present study will explore whether combining a PARP inhibitor with anti-PD1 might improve the anti-HCC impact and explain how it works. Method. The PARP inhibitor olaparib was screened out of 867 drugs through Cell Counting Kit 8 (CCK-8) assay. The expression of PARP was verified through the TCGA and TISIDB databases. The impacts exerted by PARP inhibitor olaparib to HCC cells were assessed via wound healing, Transwell, and proliferation assay. In vivo, experiments were performed in a C57BL/6 mouse model to evaluate the function of PARP inhibitor olaparib combination with anti-PD1 in HCC and mice tumors were further detected by immunohistochemically staining. Result. Olaparib was selected as the research object on the basis of drug screening. The results of the TCGA and Human Protein Atlas databases revealed that PARP was significantly upregulated in carcinoma cell cluster of HCC tissues compared to normal tissues. Higher expression of PARP showed a poorer prognosis based on Kaplan-Meier Plotter. qRT-PCR experiments confirmed that olaparib could increase PD-L1 expression through inhibiting miR-513 in HCC cells. In vivo, experiment confirmed that the combination of olaparib and anti-PD1 could enhance the immunotherapy effect of HCC. Conclusion. The present study reveals that inhibition of PARP potentiates immune checkpoint therapy through the miR-513/PD-L1 pathway in HCC and the combination of PARP inhibitor olaparib and anti-PD1 is beneficial to HCC therapy.
    Type of Medium: Online Resource
    ISSN: 1687-8469 , 1687-8450
    URL: Article
    DOI: 10.1155/2022/6988923
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2461349-6
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  • 2
    Online Resource
    Online Resource
    Diagnostic and clinical utility of next‐generation sequencing in children born with multiple congenital anomalies in the China neonatal genomes project
    Hindawi Limited ; 2021
    In:  Human Mutation Vol. 42, No. 4 ( 2021-04), p. 434-444
    Details
    In: Human Mutation, Hindawi Limited, Vol. 42, No. 4 ( 2021-04), p. 434-444
    Type of Medium: Online Resource
    ISSN: 1059-7794 , 1098-1004
    URL: Issue
    URL: Article
    DOI: 10.1002/humu.v42.4
    DOI: 10.1002/humu.24170
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 1498165-8
    SSG: 12
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  • 3
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    Online Resource
    Preclinical Pharmacokinetics, Biodistribution, and Acute Toxicity Evaluation of Caerin 1.9 Peptide in Sprague Dawley Rats
    Hindawi Limited ; 2022
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2022 ( 2022-8-2), p. 1-13
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2022 ( 2022-8-2), p. 1-13
    Abstract: Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog (Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the efficacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. This paper investigated the pharmaceutical kinetic profile, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. The results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (Cmax) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T1/2 was 4.58 hr, and AUC0-last was 1890 h × ng/mL. In female rats, Cmax was 256 ng/mL, with an average drug retention time of 2.96 hr, T1/2 of 1.33 hr, and AUC0-last of 740 h × ng/mL. The results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T1/2 extended, and Cmax, AUC0-last, and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. The results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts.
    Type of Medium: Online Resource
    ISSN: 1741-4288 , 1741-427X
    URL: Article
    DOI: 10.1155/2022/9869293
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2148302-4
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  • 4
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    Online Resource
    The Relieving Effects of a Polyherb-Based Dietary Supplement ColonVita on Gastrointestinal Quality of Life Index (GIQLI) in Older Adults with Chronic Gastrointestinal Symptoms Are Influenced by Age and Cardiovascular Disease: A 12-Week Randomized Placebo-Controlled Trial
    Hindawi Limited ; 2021
    In:  Evidence-Based Complementary and Alternative Medicine Vol. 2021 ( 2021-9-10), p. 1-13
    Details
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2021 ( 2021-9-10), p. 1-13
    Abstract: Chronic gastrointestinal symptoms (CGS) negatively affect the quality of life in about 15–30% of the population without effective drugs. Recent studies suggest that dietary supplement may improve CGS, but inconsistent results exist. The goal of this study is to evaluate the effect of a polyherbal-based supplement ColonVita on the gastrointestinal quality of life index (GIQLI) in 100 old adults with CGS (63.1 ± 9.6 years) who were randomly assigned to daily ColonVita or placebo tablets (n = 50/group) for 12 weeks in a double-blind, randomized controlled trial design. No significant fibrdifferences were found between ColonVita and placebo in the baseline total GIQLI score (101.12 ± 16.87 vs. 101.80 ± 16.48) ( P 〉 0.05 ) or postintervention total GIQLI score (114.78 ± 9.62 vs. 111.74 ± 13.01) ( P 〉 0.05 ). However, ColonVita significantly improved 16 scores of the 19 core GI symptoms compared with 10 items improved by placebo. The ColonVita group significantly improved the remission rate of 5 core GI symptoms compared to placebo and significantly improved the total GIQLI scores (118.09 ± 7.88 vs. 109.50 ± 16.71) ( P 〈 0.05 ) and core GI symptom scores (64.61 ± 3.99 vs. 60.00 ± 8.65) ( P 〈 0.05 ) in people ≥60 years of age (n = 49) but not in those under 60 y (n = 51). ColonVita significantly improved the total GIQLI scores and core GI symptom scores in people without cardiovascular diseases (CVD) (n = 56) (116.74 ± 9.38 vs. 110.10 ± 14.28) ( P 〈 0.05 ) and (63.11 ± 4.53 vs. 59.93 ± 8.03) ( P = 0.07 ), respectively, but not in those with CVD (n = 44). Thus, ColonVita was beneficial for old adults with CGS, especially those ≥60 years of age and without CVD. Because a heterogenous pathogenesis of CGS-like irritable bowel syndrome (IBS) and inflammatory bowel disease (ISD) is differentially associated with CVD, different comorbidities may have influenced the outcomes of different trials that should be controlled in further studies.
    Type of Medium: Online Resource
    ISSN: 1741-4288 , 1741-427X
    URL: Article
    DOI: 10.1155/2021/6653550
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2148302-4
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  • 5
    Online Resource
    Online Resource
    Luteolin Induces Apoptosis and Autophagy in Mouse Macrophage ANA-1 Cells via the Bcl-2 Pathway
    Hindawi Limited ; 2018
    In:  Journal of Immunology Research Vol. 2018 ( 2018-08-30), p. 1-9
    Details
    In: Journal of Immunology Research, Hindawi Limited, Vol. 2018 ( 2018-08-30), p. 1-9
    Abstract: Plants rich in luteolin have been used as Chinese traditional medicines for inflammatory diseases, hypertension, and cancer. However, little is known about the effect of luteolin on the apoptosis or autophagy of the macrophages. In this study, mouse macrophage ANA-1 cells were incubated with different concentrations of luteolin. The viability of the cells was determined by an MTT assay, apoptosis was determined by flow cytometric analysis, the level of cell autophagy was observed by confocal microscopy, and the expression levels of apoptotic or autophagic and antiapoptotic or antiautophagic proteins were detected by Western blot analysis. The results showed that luteolin decreased the viability of ANA-1 cells and induced apoptosis and autophagy. Luteolin induced apoptosis accompanied by downregulation of the expression of Bcl-2 and upregulation of the expression of caspase 3 and caspase 8. And luteolin increased FITC-LC3 punctate fluorescence accompanied by the increased expression levels of LC3-I, ATG7, and ATG12, while it suppressed the expression level of Beclin-1. Luteolin treatment resulted in obvious activation of the p38, JNK, and Akt signaling pathways, which is important in modulating apoptosis and autophagy. Thus, we concluded that luteolin induced the apoptosis and autophagy of ANA-1 cells most likely by regulating the p38, JNK, and Akt pathways, inhibiting the activity of Bcl-2 and Beclin-1 and upregulating caspase 3 and caspase 8 expression. These results provide novel insights into a therapeutic strategy to prevent and possibly treat macrophage-related diseases through luteolin-induced apoptosis and autophagy.
    Type of Medium: Online Resource
    ISSN: 2314-8861 , 2314-7156
    URL: Article
    DOI: 10.1155/2018/4623919
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2817541-4
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  • 6
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    Online Resource
    MMP2 and MMP10 Polymorphisms Are Related to Steroid-Induced Osteonecrosis of the Femoral Head among Chinese Han Population
    Hindawi Limited ; 2019
    In:  BioMed Research International Vol. 2019 ( 2019-05-05), p. 1-10
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2019 ( 2019-05-05), p. 1-10
    Abstract: Background . Steroid-induced osteonecrosis of the femoral head is a relatively serious condition which seriously reduces patient quality of life. However, the pathogenesis of steroid-induced ONFH is still unclear. In recent years, more scholars have found that the pathogenesis of steroid-induced ONFH is related to susceptibility factors such as MMPs / TIMPs system. The main purpose of this study is to investigate the correlation between MMP2 and MMP10 gene polymorphisms and steroid-induced ONFH in Chinese Han population. Methods . Six SNPs in MMP2 and two SNPs in MMP10 were genotyped using Agena MassARRAY RS1000 system from 286 patients of steroid-induced ONFH and in 309 healthy controls. The association between MMP2 and MMP10 polymorphisms and steroid-induced ONFH risk were estimated by the Chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. The relative risk was estimated by odd ratios (ORs) and 95% confidence intervals (CIs). Result . We found that the minor TG allele of rs470154 in MMP10 was associated with an increased risk of steroid-induced ONFH (OR = 1.45, 95% CI, 1.03 – 2.05, p = 0.032). In the genetic model analysis, we found that rs2241146 in MMP2 gene and rs470154 in MMP10 gene showed a statistically significant association with increased risk of steroid-induced ONFH. The six SNPs (rs470154, rs243866, rs243864, rs865094, rs11646643, and rs2241146) showed a statistically significant association with different clinical phenotypes. Conclusion . Our results verify that genetic polymorphisms of MMP2 and MMP10 contribute to steroid-induced ONFH susceptibility in the population of Chinese Han population, and our study provides new insights into the role that MMP2 and MMP10 plays in the mechanism of ONFH.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2019/8298193
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2019
    detail.hit.zdb_id: 2698540-8
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  • 7
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    Online Resource
    Caerin 1 Peptides, the Potential Jack-of-All-Trades for the Multiple Antibiotic-Resistant Bacterial Infection Treatment and Cancer Immunotherapy
    Hindawi Limited ; 2022
    In:  BioMed Research International Vol. 2022 ( 2022-4-11), p. 1-11
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2022 ( 2022-4-11), p. 1-11
    Abstract: Antibiotic resistance-related bacterial infections and cancers become huge challenges in human health in the 21st century. A number of naturally derived antimicrobial peptides possess multiple functions in host defense, including anti-infective and anticancer activities. One of which is known as the caerin 1 family peptides. The microbicidal properties of these peptides have been long discussed. The recent studies also established the usage of two members in this family, caerin 1.1 and caerin 1.9, in antimultiple antibiotic-resistant bacteria species. It is increasingly evident that caerin 1.1 and caerin 1.9 also contain additional activities in the suppression of tumor. In this review, we briefly outline the therapeutic potentials and possible mechanism of action of caerin 1.1 and 1.9 in the treatment of multiple antibiotic-resistant bacterial infection and cancer immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2314-6141 , 2314-6133
    URL: Article
    DOI: 10.1155/2022/7841219
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2698540-8
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  • 8
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    Online Resource
    Regulation of Long Noncoding RNAs Responsive to Phytoplasma Infection in Paulownia tomentosa
    Hindawi Limited ; 2018
    In:  International Journal of Genomics Vol. 2018 ( 2018), p. 1-16
    Details
    In: International Journal of Genomics, Hindawi Limited, Vol. 2018 ( 2018), p. 1-16
    Abstract: Paulownia witches’ broom caused by phytoplasma infection affects the production of Paulownia trees worldwide. Emerging evidence showed that long noncoding RNAs (lncRNA) play a protagonist role in regulating the expression of genes in plants. So far, the identification of lncRNAs has been limited to a few model plant species, and their roles in mediating responses to Paulownia tomentosa that free of phytoplasma infection are yet to be characterized. Here, whole-genome identification of lncRNAs, based on strand-specific RNA sequencing, from four Paulownia tomentosa samples, was performed and identified 3689 lncRNAs. These lncRNAs showed low conservation among plant species and some of them were miRNA precursors. Further analysis revealed that the 112 identified lncRNAs were related to phytoplasma infection. We predicted the target genes of these phytoplasma-responsive lncRNAs, and our analysis showed that 51 of the predicted target genes were alternatively spliced. Moreover, we found the expression of the lncRNAs plays vital roles in regulating the genes involved in the reactive oxygen species induced hypersensitive response and effector-triggered immunity in phytoplasma-infected Paulownia. This study indicated that diverse sets of lncRNAs were responsive to Paulownia witches’ broom, and the results will provide a starting point to understand the functions and regulatory mechanisms of Paulownia lncRNAs in the future.
    Type of Medium: Online Resource
    ISSN: 2314-436X , 2314-4378
    URL: Article
    DOI: 10.1155/2018/3174352
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2711883-6
    SSG: 12
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  • 9
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    Online Resource
    Cover, Volume 42, Issue 4
    Hindawi Limited ; 2021
    In:  Human Mutation Vol. 42, No. 4 ( 2021-04)
    Details
    In: Human Mutation, Hindawi Limited, Vol. 42, No. 4 ( 2021-04)
    Type of Medium: Online Resource
    ISSN: 1059-7794 , 1098-1004
    URL: Issue
    URL: Article
    DOI: 10.1002/humu.v42.4
    DOI: 10.1002/humu.24202
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 1498165-8
    SSG: 12
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  • 10
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    Online Resource
    Hyperglycemia and Correlated High Levels of Inflammation Have a Positive Relationship with the Severity of Coronavirus Disease 2019
    Hindawi Limited ; 2021
    In:  Mediators of Inflammation Vol. 2021 ( 2021-3-18), p. 1-9
    Details
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2021 ( 2021-3-18), p. 1-9
    Abstract: Objective. Coronavirus disease 2019 (COVID-19) is a considerable global public health threat. This study sought to investigate whether blood glucose (BG) levels or comorbid diabetes are associated with inflammatory status and disease severity in patients with COVID-19. Methods. In this retrospective cohort study, the clinical and biochemical characteristics of COVID-19 patients with or without diabetes were compared. The relationship among severity of COVID-19, inflammatory status, and diabetes or hyperglycemia was analyzed. The severity of COVID-19 in all patients was determined according to the diagnostic and treatment guidelines issued by the Chinese National Health Committee (7th edition). Results. Four hundred and sixty-one patients were enrolled in our study, and 71.58% of patients with diabetes and 13.03% of patients without diabetes had hyperglycemia. Compared with patients without diabetes ( n = 366 ), patients with diabetes ( n = 95 ) had a higher leucocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR). There was no association between severity of COVID-19 and known diabetes adjusted for age, sex, body mass index (BMI), known hypertension, and coronary heart disease. The leucocyte count, NLR, and C-reactive protein (CRP) level increased with increasing BG level. Hyperglycemia was an independent predictor of critical (OR 4.00, 95% CI 1.72-9.30) or severe (OR 3.55, 95% CI 1.47-8.58) COVID-19, and of increased inflammatory levels (high leucocyte count (OR 4.26, 95% CI 1.65-10.97), NLR (OR 2.76, 95% CI 1.24-6.10), and CRP level (OR 2.49, 95% CI 1.19-5.23)), after adjustment for age, sex, BMI, severity of illness, and known diabetes. Conclusion. Hyperglycemia was positively correlated with higher inflammation levels and more severe illness, and it is a risk factor for the increased severity of COVID-19. The initial measurement of plasma glucose levels after hospitalization may help identify a subset of patients who are predisposed to a worse clinical course.
    Type of Medium: Online Resource
    ISSN: 1466-1861 , 0962-9351
    URL: Article
    DOI: 10.1155/2021/8812304
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2008065-7
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