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  • Frontiers Media SA  (76)
  • 1
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 15 ( 2021-3-4)
    Abstract: Oxidative stress plays an important role in the pathogenesis of hypertension. Oligomeric proantho cyanidins (OPC) is the main polyphenol presents in grape seed and is known for its potent antioxidant and anti-inflammatory properties. In the present study, we hypothesize that OPC can attenuate oxidative stress in the paraventricular nucleus of hypothalamus (PVN), ameliorate neurotransmitter imbalance, decrease the blood pressure and sympathetic activity in renovascular hypertensive rats. After induction of renovascular hypertension by the two-kidney one-clip (2K-1C) method, male Sprague-Dawley rats received chronic bilateral PVN infusion of OPC (20 μg/h) or vehicle via osmotic minipump for 4 weeks. We found that hypertension induced by 2K-1C was associated with the production of reactive oxygen species (ROS) in the PVN. Infusion of OPC in the PVN significantly reduced the systolic blood pressure and norepinephrine in plasma of 2K-1C rats. In addition, PVN infusion of OPC decreased the level of ROS and the expression of stress-related nicotinamide adenine dinucleotide phosphate (NADPH) oxidases subunit NOX4, increased the levels of nuclear factor E2-related factor 2 (Nrf2) and antioxidant enzyme, balanced the content of cytokines, increased expression of glutamic acid decarboxylase and decreased the expression of tyrosine hydroxylase in the PVN of 2K-1C rats. Our findings provided strong evidence that PVN infusion of OPC inhibited the progression of renovascular hypertension through its potent anti-oxidative and anti-inflammatory function in the PVN.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2411902-7
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2020-12-10)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2020-12-10)
    Abstract: One of the major features of prostate cancer (PCa) is its heterogeneity, which often leads to uncertainty in cancer diagnostics and unnecessary biopsies as well as overtreatment of the disease. Novel non-invasive tests using multiple biomarkers that can identify clinically high-risk cancer patients for immediate treatment and monitor patients with low-risk cancer for active surveillance are urgently needed to improve treatment decision and cancer management. In this study, we identified 14 promising biomarkers associated with PCa and tested the performance of these biomarkers on tissue specimens and pre-biopsy urinary sediments. These biomarkers showed differential gene expression in higher- and lower-risk PCa. The 14-Gene Panel urine test ( PMP22 , GOLM1 , LMTK2 , EZH2 , GSTP1 , PCA3 , VEGFA , CST3 , PTEN , PIP5K1A , CDK1 , TMPRSS2 , ANXA3 , and CCND1 ) was assessed in two independent prospective and retrospective urine study cohorts and showed high diagnostic accuracy to identify higher-risk PCa patients with the need for treatment and lower-risk patients for surveillance. The AUC was 0.897 (95% CI 0.939–0.855) in the prospective cohort ( n = 202), and AUC was 0.899 (95% CI 0.964–0.834) in the retrospective cohort ( n = 97). In contrast, serum PSA and Gleason score had much lower accuracy in the same 202 patient cohorts [AUC was 0.821 (95% CI 0.879–0.763) for PSA and 0.860 (95% CI 0.910–0.810) for Gleason score] . In addition, the 14-Gene Panel was more accurate at risk stratification in a subgroup of patients with Gleason scores 6 and 7 in the prospective cohort ( n = 132) with AUC of 0.923 (95% CI 0.968–0.878) than PSA [AUC of 0.773 (95% CI 0.852–0.794)] and Gleason score [AUC of 0.776 (95% CI 0.854–0.698)] . Furthermore, the 14-Gene Panel was found to be able to accurately distinguish PCa from benign prostate with AUC of 0.854 (95% CI 0.892–0.816) in a prospective urine study cohort ( n = 393), while PSA had lower accuracy with AUC of 0.652 (95% CI 0.706–0.598). Taken together, the 14-Gene Panel urine test represents a promising non-invasive tool for detection of higher-risk PCa to aid treatment decision and lower-risk PCa for active surveillance.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2737824-X
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-3-15)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-15)
    Abstract: The human placenta is a unique temporary organ with a mysterious immune tolerance. The formation of trophoblast organoids has advanced the study of placental development. HLA-G is uniquely expressed in the extravillous trophoblast (EVT) and has been linked to placental disorders. With older experimental methodologies, the role of HLA-G in trophoblast function beyond immunomodulation is still contested, as is its role during trophoblast differentiation. Organoid models incorporating CRISPR/Cas9 technology were used to examine the role of HLA-G in trophoblast function and differentiation. JEG-3 trophoblast organoids (JEG-3-ORGs) were established that highly expressed trophoblast representative markers and had the capacity to differentiate into EVT. CRISPR/Cas9 based on HLA-G knockout (KO) significantly altered the trophoblast immunomodulatory effect on the cytotoxicity of natural killer cells, as well as the trophoblast regulatory effect on HUVEC angiogenesis, but had no effect on the proliferation and invasion of JEG-3 cells and the formation of TB-ORGs. RNA-sequencing analysis further demonstrated that JEG-3 KO cells followed similar biological pathways as their wild-type counterparts during the formation of TB-ORGs. In addition, neither HLA-G KO nor the exogenous addition of HLA-G protein during EVT differentiation from JEG-3-ORGs altered the temporal expression of the known EVT marker genes. Based on the JEG-3 KO (disruption of exons 2 and 3) cell line and the TB-ORGs model, it was determined that HLA-G has a negligible effect on trophoblast invasion and differentiation. Despite this, JEG-3-ORG remains a valuable model for studying trophoblast differentiation.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 4
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 13 ( 2019-10-24)
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2411902-7
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  • 5
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-1-31)
    Abstract: Chimeric Antigen Receptor T cell(CAR T-cell) therapy has been a great success in relapsed/refractory acute B lymphoblastic leukemia and B-cell lymphoma. At the same time, there are also related adverse reactions, especially cytokine release syndrome(CRS) and immune effector cell associated neurotoxicity syndrome(ICANS). However, Double CRS caused by CRA T cells are very rare. Case report Here, we report a 33-year-male with secondary central diffuse large B-cell lymphoma(CNSL) who develpoed double CRS following sequential infusion of Anti-CD22 and Anti-CD19 CAR T cells after autologous hematopoietic stem cell transplantation(ASCT). On d+5, the patient developed high fever, along with chilly sensation, shivering, headache, blood oxygen desaturation, shock, weakness, severe thirst, and heart rate decline. IL-6 and ferritin increased significantly. The patient was diagnosed with the first CRS (grade 3). On d+36, the patient again had a persistent fever(T & gt;39C) and limbs rash. IL-6 and ferritin again increased significantly on d+38. After exclusion of infection, a diagnosis of double CRS was made. The patient’s symptoms were completely relieved after receiving tocilizumab, glucocorticoids, and other supportive treatments on d+45.On d+90, contrast-enhanced MR angiogram shows that the lesion basically disappeared, indicating the patient had achieved CR. At the end of the follow-up at d+150, the patient was functioning normally without any sequelae. Conclusion This is the first reported case worldwide where the patient with secondary CNSL suffered double CRS after CAR T-cell infusion. Our findings showed that it is important to increase awareness of early detection and diagnosis of double CRS and adopt appropriate treatment strategies.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 6
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-5-23)
    Abstract: Rearrangements of the Mixed Lineage Leukemia ( MLL/KMT2A ) gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome. Driven by the unmet need to develop better therapies for KMT2A-rearranged leukemia, we previously discovered that the novel anti-cancer agent, curaxin CBL0137, induces decondensation of chromatin in cancer cells, delays leukemia progression and potentiates standard of care chemotherapies in preclinical KMT2A-rearranged leukemia models. Based on the promising potential of histone deacetylase (HDAC) inhibitors as targeted anti-cancer agents for KMT2A-rearranged leukemia and the fact that HDAC inhibitors also decondense chromatin via an alternate mechanism, we investigated whether CBL0137 could potentiate the efficacy of the HDAC inhibitor panobinostat in KMT2A-rearranged leukemia models. The combination of CBL0137 and panobinostat rapidly killed KMT2A-rearranged leukemia cells by apoptosis and significantly delayed leukemia progression and extended survival in an aggressive model of MLL-AF9 ( KMT2A:MLLT3 ) driven murine acute myeloid leukemia. The drug combination also exerted a strong anti-leukemia response in a rapidly progressing xenograft model derived from an infant with KMT2A-rearranged acute lymphoblastic leukemia, significantly extending survival compared to either monotherapy. The therapeutic enhancement between CBL0137 and panobinostat in KMT2A-r leukemia cells does not appear to be mediated through cooperative effects of the drugs on KMT2A rearrangement-associated histone modifications. Our data has identified the CBL0137/panobinostat combination as a potential novel targeted therapeutic approach to improve outcome for KMT2A-rearranged leukemia.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2017
    In:  British Journal of Biomedical Science Vol. 74, No. 3 ( 2017-07-03), p. 127-132
    In: British Journal of Biomedical Science, Frontiers Media SA, Vol. 74, No. 3 ( 2017-07-03), p. 127-132
    Type of Medium: Online Resource
    ISSN: 0967-4845
    Language: English
    Publisher: Frontiers Media SA
    Publication Date: 2017
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  • 8
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 14 ( 2023-3-3)
    Abstract: The real-time polymerase chain reaction (PCR), commonly known as quantitative PCR (qPCR), is increasingly common in environmental microbiology applications. During the COVID-19 pandemic, qPCR combined with reverse transcription (RT-qPCR) has been used to detect and quantify SARS-CoV-2 in clinical diagnoses and wastewater monitoring of local trends. Estimation of concentrations using qPCR often features a log-linear standard curve model calibrating quantification cycle ( Cq ) values obtained from underlying fluorescence measurements to standard concentrations. This process works well at high concentrations within a linear dynamic range but has diminishing reliability at low concentrations because it cannot explain “non-standard” data such as Cq values reflecting increasing variability at low concentrations or non-detects that do not yield Cq values at all. Here, fundamental probabilistic modeling concepts from classical quantitative microbiology were integrated into standard curve modeling approaches by reflecting well-understood mechanisms for random error in microbial data. This work showed that data diverging from the log-linear regression model at low concentrations as well as non-detects can be seamlessly integrated into enhanced standard curve analysis. The newly developed model provides improved representation of standard curve data at low concentrations while converging asymptotically upon conventional log-linear regression at high concentrations and adding no fitting parameters. Such modeling facilitates exploration of the effects of various random error mechanisms in experiments generating standard curve data, enables quantification of uncertainty in standard curve parameters, and is an important step toward quantifying uncertainty in qPCR-based concentration estimates. Improving understanding of the random error in qPCR data and standard curve modeling is especially important when low concentrations are of particular interest and inappropriate analysis can unduly affect interpretation, conclusions regarding lab performance, reported concentration estimates, and associated decision-making.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587354-4
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  • 9
    In: Frontiers in Virology, Frontiers Media SA, Vol. 2 ( 2022-11-10)
    Abstract: Nipah virus (NiV) is a re-emerging pathogen that causes severe disease in animals and humans. Current treatment measures for NiV infection are insufficient, and there is no approved vaccine against NiV for either humans or animals. Nipah virus is listed as a high-priority pathogen for vaccine and therapeutic research by the World Health Organization (WHO). In the present study, we employed synthetic enhanced DNA technologies developed to design and produce novel consensus NiV Fusion (NiV-F) and Glycoprotein (NiV-G) antigen sequences for inclusion in synthetic DNA vaccines for NiV. The expression of each vaccine antigen was confirmed in vitro using immune-binding assays. Electroporation-enhanced intramuscular injection of each NiV-F and NiV-G into mice induced potent cellular immune responses to multiple epitopes of NiV-G and NiV-F that included antigen-specific CD8 + T cells. Both vaccines elicited high antibody titers in mice, with a single immunization sufficient to seroconvert 100% of immunized animals. Additionally, the NiV-F vaccine also induced antibodies to neutralize NiV-F-pseudotyped virus particles. These data support further study of these novel synthetic enhanced NiV nucleic acid-based antigens as potential components of an effective vaccine against the Nipah virus.
    Type of Medium: Online Resource
    ISSN: 2673-818X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 3100943-8
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Microbiology Vol. 12 ( 2021-7-20)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 12 ( 2021-7-20)
    Abstract: The precious rare edible fungus Morchella conica is popular worldwide for its rich nutrition, savory flavor, and varieties of bioactive components. Due to its high commercial, nutritional, and medicinal value, it has always been a hot spot. However, the molecular mechanism and endophytic bacterial communities in M. conica were poorly understood. In this study, we sequenced, assembled, and analyzed the genome of M. conica SH. Transcriptome analysis reveals significant differences between the mycelia and fruiting body. As shown in this study, 1,329 and 2,796 genes were specifically expressed in the mycelia and fruiting body, respectively. The Gene Ontology (GO) enrichment showed that RNA polymerase II transcription activity-related genes were enriched in the mycelium-specific gene cluster, and nucleotide binding-related genes were enriched in the fruiting body-specific gene cluster. Further analysis of differentially expressed genes in different development stages resulted in finding two groups with distinct expression patterns. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment displays that glycan degradation and ABC transporters were enriched in the group 1 with low expressed level in the mycelia, while taurine and hypotaurine metabolismand tyrosine metabolism-related genes were significantly enriched in the group 2 with high expressed level in mycelia. Moreover, a dynamic shift of bacterial communities in the developing fruiting body was detected by 16S rRNA sequencing, and co-expression analysis suggested that bacterial communities might play an important role in regulating gene expression. Taken together, our study provided a better understanding of the molecular biology of M. conica SH and direction for future research on artificial cultivation.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587354-4
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