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  • 11
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 7 ( 2018-04-01), p. 1779-1791
    Abstract: Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here that metformin treatment blocks the suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating the expression and ectoenzymatic activity of CD39 and CD73 on monocytic and polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated protein kinase α and subsequently suppressed hypoxia-inducible factor α, which was critical for induction of CD39/CD73 expression in MDSC. Furthermore, metformin treatment correlated with longer overall survival in diabetic patients with ovarian cancer, which was accompanied by a metformin-induced reduction in the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the antitumor activities of circulating CD8+ T cells. Our results highlight a direct effect of metformin on MDSC and suggest that metformin may yield clinical benefit through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent MDSC immunosuppression in ovarian cancer patients. Significance: The antitumor activity of an antidiabetes drug is attributable to reduced immunosuppressive activity of myeloid-derived tumor suppressor cells. Cancer Res; 78(7); 1779–91. ©2018 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 12
    In: Journal of Viral Hepatitis, Wiley, Vol. 26, No. 2 ( 2019-02), p. 246-257
    Abstract: Myeloid‐derived suppressor cells (MDSCs) have been described as suppressors of T‐cell function in many malignancies. Impaired T‐cell responses have been observed in patients with chronic hepatitis C virus infection (CHC), which is reportedly associated with the establishment of persistent HCV infection. Therefore, we hypothesized that MDSCs also play a role in chronic HCV infection. MDSCs in the peripheral blood of 206 patients with CHC and 20 healthy donors were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) of healthy donors cultured with hepatitis C virus core protein (HCVc) were stimulated with or without interleukin 10 (IL‐10). Compared to healthy donors and certain CHC patients with sustained viral response (SVR), CHC patients without SVR presented with a dramatic elevation of G‐MDSCs with the HLA‐DR −/low CD33 + CD14 − CD11b + phenotype in peripheral blood. The frequency of G‐MDSCs in CHC patients was positively correlated with serum HCVc, and G‐MDSCs were induced from healthy PBMCs by adding exogenous HCVc. Furthermore, we revealed a potential mechanism by which HCVc mediates G‐MDSC polarization; activation of ERK1/2 resulting in IL‐10 production and IL‐10‐activated STAT3 signalling. Finally, we confirmed that HCVc‐induced G‐MDSCs suppress the proliferation and production of IFN‐γ in autologous T‐cells. We also found that the frequency of G‐MDSCs in serum was associated with CHC prognosis. HCVc maintains immunosuppression by promoting IL‐10/STAT3‐dependent differentiation of G‐MDSCs from PBMCs, resulting in the impaired functioning of T‐cells. G‐MDSCs may thus be a promising biomarker for predicting prognosis of CHC patients.
    Type of Medium: Online Resource
    ISSN: 1352-0504 , 1365-2893
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2007924-2
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  • 13
    In: Journal of Evidence-Based Medicine, Wiley, Vol. 14, No. 4 ( 2021-12), p. 313-332
    Abstract: The coronavirus disease 2019 (COVID‐19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID‐19 pandemic. Purpose We aimed to develop a living evidence‐based guideline of integrating Chinese and western medicine for COVID‐19. Study design Living evidence‐based guideline. Methods This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. Results The first version of this living guidance focuses on patients who are mild or moderate COVID‐19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face‐to‐face experts’ consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. Conclusion This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID‐19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID‐19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.
    Type of Medium: Online Resource
    ISSN: 1756-5383 , 1756-5391
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 14
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2021
    In:  Journal of Neuroinflammation Vol. 18, No. 1 ( 2021-12)
    In: Journal of Neuroinflammation, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2021-12)
    Abstract: Innate immunity can facilitate early brain injury (EBI) following subarachnoid hemorrhage (SAH). Numerous studies suggest that pyroptosis could exacerbate extracellular immune responses by promoting secretion of inflammatory cytokines. Transforming growth factor-β-activated kinase 1 (TAK1) is a quintessential kinase that positively regulates inflammation through NF-κB and MAPK signaling cascades. However, the effects of TAK1 on neuroinflammation in EBI following SAH are largely unknown. Methods Two hundred and forty-six male C57BL/6J mice were subjected to the endovascular perforation model of SAH. A selective TAK1 inhibitor, 5Z-7-oxozeaenol (OZ) was administered by intracerebroventricular (i.c.v) injection at 30 min after SAH induction. To genetic knockdown of TAK1, small interfering RNA (siRNA) was i.c.v injected at 48 h before SAH induction. SAH grade, brain water content, BBB permeability, neurological score, western blot, real-time PCR, ELISA, transmission electron microscope, and immunofluorescence staining were performed. Long-term behavioral sequelae were evaluated by the rotarod and Morris water maze tests. Furthermore, OZ was added to the culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. The reactive oxygen species level was detected by DCFH-DA staining. Lysosomal integrity was assessed by Lyso-Tracker Red staining and Acridine Orange staining. Results The neuronal phosphorylated TAK1 expression was upregulated following SAH. Pharmacologic inhibition of TAK1 with OZ could alleviate neurological deficits, brain edema, and brain-blood barrier (BBB) disruption at 24 h after SAH. In addition, OZ administration restored long-term neurobehavioral function. Furthermore, blockade of TAK1 dampened neuronal pyroptosis by downregulating the N-terminal fragment of GSDMD (GSDMD-N) expression and IL-1β/IL-18 production. Mechanistically, both in vivo and in vitro, we demonstrated that TAK1 can induce neuronal pyroptosis through promoting nuclear translocation of NF-κB p65 and activating nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. TAK1 siRNA treatment mitigated SAH-induced neurobehavioral deficits and restrained phosphorylated NF-κB p65 expression and NLRP3 inflammasome activation. TAK1 blockade also ameliorated reactive oxygen species (ROS) production and prevented lysosomal cathepsin B releasing into the cytoplasm. Conclusions Our findings demonstrate that TAK1 modulates NLRP3-mediated neuronal pyroptosis in EBI following SAH. Inhibition of TAK1 may serve as a potential candidate to relieve neuroinflammatory responses triggered by SAH.
    Type of Medium: Online Resource
    ISSN: 1742-2094
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 15
    Online Resource
    Online Resource
    Elsevier BV ; 2015
    In:  Journal of Functional Foods Vol. 17 ( 2015-08), p. 958-968
    In: Journal of Functional Foods, Elsevier BV, Vol. 17 ( 2015-08), p. 958-968
    Type of Medium: Online Resource
    ISSN: 1756-4646
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
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  • 16
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 12 ( 2022-12-20)
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-12-20)
    Abstract: The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious medical problem worldwide. Acquired OXA-48-like carbapenemases encoded by plasmids are important causes of carbapenem resistance in K. pneumoniae . To explore the links between plasmids and bla OXA-48 -like genes in K. pneumoniae , we systematically analyzed the variants of bla OXA-48 -like plasmid replicon types, phylogenetic patterns, geographic distribution, conjugative transfer regions, and the genetic environments surrounding bla OXA-48 -like of 191 bla OXA-48 -like-harboring plasmids, which were identified from 4451 plasmids of K. pneumoniae downloaded from GenBank. Our results showed that seven different variants of bla OXA-48 -like genes were identified from the 191 bla OXA-48 -like-harboring plasmids in K. pneumoniae , with bla OXA-48 , bla OXA-232 , and bla OXA-181 being highly prevalent. In K. pneumoniae , bla OXA-48 was mainly carried by the composite transposon Tn 1999.2 located on IncL/M-type conjugative plasmids, which were mainly geographically distributed in Switzerland, Germany, and China. In K. pneumoniae , the bl a OXA-232 gene was mainly carried by 6.1-kb ColKP3-type mobilizable plasmids, which were mainly isolated in India. In K. pneumoniae , bla OXA-181 was mainly carried by a group of 50-kb ColKP3-IncX3 hybrid conjugative plasmids and a group of small ColKP3-type mobilizable plasmids with lengths of 5.9–9.3 kb, the former was sporadically discovered in China, South Korea, India, and Czech Republic, while the latter was almost all isolated in India. In addition, five bla OXA-245 -harboring 65.9-kb IncL plasmids of K. pneumoniae isolated in Spain were found to have the genetic context of bla OXA-245 more complicated than that of bla OXA-48 -harboring IncL/M-type plasmids, with two copies of IS 1R inserted both upstream and downstream of bla OXA-245 - lysR . These findings enhance our understanding of the genetic diversity of bla OXA-48 -like-harboring plasmids in K. pneumoniae .
    Type of Medium: Online Resource
    ISSN: 2235-2988
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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  • 17
    In: International Journal of Genomics, Hindawi Limited, Vol. 2021 ( 2021-6-16), p. 1-28
    Abstract: Current data is scarce regarding the function of noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in the interferon- (IFN-) mediated immune response. This is a comprehensive study that analyzes the lncRNA and miRNA expression profiles of the type I IFN and type II IFN in porcine alveolar macrophages using RNA sequencing. There was a total of 152 overexpressed differentially expressed (DE) lncRNAs and 21 DE miRNAs across type I IFN and type II IFN in porcine alveolar macrophages. Subsequent lncRNA-miRNA-mRNA network construction revealed the involvement of 36 DE lncRNAs and 12 DE miRNAs. LncRNAs such as the XLOC_211306, XLOC_100516, XLOC_00695, XLOC_149196, and XLOC_014459 were expressed at a higher degree in the type I IFN group, while XLOC_222640, XLOC_047290, XLOC_147777, XLOC_162298, XLOC_220210, and XLOC_165237 were expressed at a higher degree in the type II IFN group. These lncRNAs were found to act as “sponges” for miRNAs such as miR-34a, miR-328, miR-885-3p, miR-149, miR-30c-3p, miR-30b-5p, miR-708-5p, miR-193a-5p, miR-365-5p, and miR-7. Their target genes FADS2, RPS6KA1, PIM1, and NOD1 were found to be associated with several immune-related signaling pathways including the NOD-like receptor, Jak-STAT, mTOR, and PPAR signaling pathways. These experiments provide a comprehensive profile of overexpressed noncoding RNAs in porcine alveolar macrophages, providing new insights regarding the IFN-mediated immune response.
    Type of Medium: Online Resource
    ISSN: 2314-4378 , 2314-436X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2711883-6
    SSG: 12
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  • 18
    In: Oncology Reports, Spandidos Publications, Vol. 33, No. 1 ( 2015-1), p. 425-432
    Type of Medium: Online Resource
    ISSN: 1021-335X , 1791-2431
    Language: English
    Publisher: Spandidos Publications
    Publication Date: 2015
    detail.hit.zdb_id: 1222484-4
    detail.hit.zdb_id: 2120548-6
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  • 19
    Online Resource
    Online Resource
    Walter de Gruyter GmbH ; 2022
    In:  Oncologie Vol. 24, No. 4 ( 2022), p. 679-691
    In: Oncologie, Walter de Gruyter GmbH, Vol. 24, No. 4 ( 2022), p. 679-691
    Type of Medium: Online Resource
    ISSN: 1292-3818
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2022
    detail.hit.zdb_id: 2145843-1
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  • 20
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Vol. 379, No. 6634 ( 2023-02-24), p. 820-825
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6634 ( 2023-02-24), p. 820-825
    Abstract: A group of neurons encodes past sexual experience and has long-lasting effects on mating decisions in both sexes in mice.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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