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  • Frontiers Media SA  (14)
  • 1
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-8-23)
    Abstract: Accumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database. Methods We selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002–2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates. Results The incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04–1.19), 28% (95% CI = 1.19–1.37), or 64% (95% CI = 1.41–1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group. Conclusion The present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 2
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2023-1-13)
    Abstract: Natural killer (NK) cells are immune effector cells with outstanding features for adoptive immunotherapy. Immune effector cells with chimeric antigen receptors (CARs) are promising targeted therapeutic agents for various diseases. Because tumor cells exhibit heterogeneous antigen expression and lose cell surface antigen expression during malignant progression, many CARs fixed against only one antigen have limited efficacy and are associated with tumor relapse. To expand the utility of CAR-NK cells, we designed a split and universal cotinine-CAR (Cot-CAR) system, comprising a Cot-conjugator and NK92 cells (α-Cot-NK92 cells) engineered with a CAR containing an anti-Cot-specific single-chain variable fragment and intracellular signaling domain. The efficacy of the Cot-CAR system was assessed in vitro using a cytolysis assay against various tumor cells, and its single- or multiple- utility potential was demonstrated using an in vivo lung metastasis model by injecting A549-Red-Fluc cells. The α-Cot-NK92 cells could switch targets, logically respond to multiple antigens, and tune cytolytic activation through the alteration of conjugators without re-engineering. Therefore the universal Cot-CAR system is useful for enhancing specificity and diversity of antigens, combating relapse, and controlling cytolytic activity. In conclusion, this universal Cot-CAR system reveals that multiple availability and controllability can be generated with a single, integrated system.
    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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  • 3
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 9 ( 2022-9-15)
    Abstract: Sepsis is a systemic inflammatory disease to infections and results in tissue damage and multiple organ failure. Ponciri Fructus Immaturus (PFI) is widely used in traditional medicine for allergic inflammation and gastrointestinal disorders. However, the effect of PFI on sepsis is still unknown. This study investigated the anti-inflammatory and antiseptic effects of PFI ethanol extract (PFIE) in LPS-stimulated J774 macrophages and mice with CLP- or LPS-induced sepsis, respectively. PFIE attenuates the LPS-induced production of the proinflammatory mediator NO by inhibiting the expression of iNOS in J774 cells. Real-time RT-PCR data and ELISA showed that the mRNA and protein levels of TNF-α, IL-1β, and IL-6 increased in LPS-stimulated J774 cells. However, this induction was significantly suppressed in PFIE pre-treated J774 cells. We also found that PFIE administration increased the survival rate of mice with LPS- and CLP-induced sepsis. Decreased serum levels of AST, ALT, and CK were observed after administration of PFIE, which was associated with reduced production of proinflammatory factors, such as NO, TNF-α, IL-1β, and IL-6. Moreover, PFIE suppressed the phosphorylation and nuclear translocation of STAT1 in LPS-stimulated J774 cells, suggesting that PFIE can inhibit LPS- and CLP-induced septic shock by suppressing the STAT1 activation. These findings provide the potential therapeutic relevance of PFIE in treating acute inflammatory disease.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2776676-7
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Microbiology Vol. 11 ( 2020-10-30)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 11 ( 2020-10-30)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587354-4
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  • 5
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 11 ( 2023-4-13)
    Abstract: YME1L1, a mitochondrial metalloproteinase, is an Adenosine triphosphate (ATP)-dependent metalloproteinase and locates in the mitochondrial inner membrane. The protease domain of YME1L1 is oriented towards the mitochondrial intermembrane space, which modulates the mitochondrial GTPase optic atrophy type 1 (OPA1) processing. However, during embryonic development, there is no report yet about the role of YME1L1 on mitochondrial biogenesis and function in pigs. In the current study, the mRNA level of YME1L1 was knocked down by double strand RNA microinjection to the 1-cell stage embryos. The expression patterns of YME1L1 and its related proteins were performed by immunofluorescence and western blotting. To access the biological function of YME1L1, we first counted the preimplantation development rate, diameter, and total cell number of blastocyst on day-7. First, the localization of endogenous YME1L1 was found in the punctate structures of the mitochondria, and the expression level of YME1L1 is highly expressed from the 4-cell stage. Following significant knock-down of YME1L1, blastocyst rate and quality were decreased, and mitochondrial fragmentation was induced. YME1L1 knockdown induced excessive ROS production, lower mitochondrial membrane potential, and lower ATP levels. The OPA1 cleavage induced by YME1L1 knockdown was prevented by double knock-down of YME1L1 and OMA1. Moreover, cytochrome c , a pro-apoptotic signal, was released from the mitochondria after the knock-down of YME1L1. Taken together, these results indicate that YME1L1 is essential for regulating mitochondrial fission, function, and apoptosis during porcine embryo preimplantation development.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2737824-X
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-4-19)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-4-19)
    Abstract: Oocyte (OC), embryo (EC), and ovarian tissue cryopreservation (OTC) are options for fertility preservation (FP) before going through gonadotoxic cancer treatment, or anticipated fertility decline in benign ovarian diseases, or for planned OC. The aim of this study is to report outcomes of FP in a single tertiary hospital in Korea. Methods This is a retrospective study of OC, EC, and OTC cycles. All patients who visited or were referred to the infertility clinic at the Department of Obstetrics and Gynecology for the purpose of FP between 2010 and October 2021 were included. Results A total of 564 controlled ovarian stimulation cycles were conducted in 416 women. Three hundred fifty-seven women underwent 494 OC cycles. Most patients were diagnosed with breast cancer (22.4%), followed by endometriomas (21.9%), and then by planned OC (20.7%). Cases of OC have increased over the years, peaking at 109 cycles in 2019 compared to one in 2010. Fifty-nine women underwent 70 EC cycles, and breast cancer (50.8%) was the most common indication. Repetitive OC and EC cycles were undergone in 92 and 9 women, respectively (mean number of repetition, 1.37 and 1.19 times in OC and EC, respectively), yielding a maximum number of 33 oocytes or 23 embryos being cryopreserved per patient. The utilization rate was 3.1% (11/357) in OC and 16.9% (10/59) in EC. Twenty-six women underwent OTC, and gynecologic cancer was the most common indication (9/26, 34.6%). One woman had the cryopreserved ovarian tissue retransplanted and successfully generated embryos. Conclusion OC, EC, and OTC are possible options for preserving fertility, and these opportunities should be provided for women at risk of fertility decline or those who are eager to protect their future fertility. This is the first report on long-term FP outcomes in a single tertiary center in Korea. We expect that there will be more cases over the years and more women returning to use their gametes or embryos for pregnancy.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 7
    In: Frontiers in Chemistry, Frontiers Media SA, Vol. 10 ( 2022-12-5)
    Abstract: Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8 + T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8 + T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8 + T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1.
    Type of Medium: Online Resource
    ISSN: 2296-2646
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711776-5
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  • 8
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-5-28)
    Abstract: The occurrence of ice crystallization during ovarian tissue (OT) cryopreservation causes unavoidable cryodamage, and ice recrystallization during the warming is more detrimental than ice crystallization. Here, we investigated that antifreeze protein (AFP) treatment during the warming procedure can improve the bovine OT quality after xenotransplantation (XT). Bovine OTs (n=120) were evenly assigned to four groups: fresh, vitrified-warmed, vitrified-warmed with 10 mg/mL Leucosporidium ice-binding protein (LeIBP, a type of AFP) (LeIBP-10), and vitrified-warmed with 20 mg/mL LeIBP (LeiBP-20). LeIBPs were added to the first warming solution. Twenty pieces of OTs were assigned to each category. The remaining 10 OTs from each category were assigned to the XT-Fresh control, XT-Vitrified-warmed control, XT-LeIBP-10, and XT-LeIBP-20 groups, respectively, and xenotransplanted to 9-week-old ovariectomized nude mice for one week. LeIBP treatment during the warming step increased morphological follicle normality and decreased apoptotic follicle ratios after vitrification-warming and XT. The XT-vitrified-warmed control group showed significantly reduced microvessel density and increased fibrosis when compared to that of the XT-fresh group. Microvessel density and fibrosis were recovered in both LeIBP treated groups. There was no significant difference between the LeIBP-10 and LeIBP-20 groups in all outcomes. AFP treatment during the warming procedure can prevent OT damage, and improve ovarian follicle morphology and apoptosis in both the vitrified-warmed bovine OT and its graft. After confirmation in a human study, AFPs can potentially be applied to human OT cryopreservation to reduce cryodamage and improve the OT quality.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2592084-4
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  • 9
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-12-15)
    Abstract: Endometrioma is known to reduce the ovarian reserve and the extent of the decrease is more severe when ovarian surgery is performed. Therefore, to prevent this decline in fertility, patients with endometrioma are considered candidates for preoperative fertility preservation (FP). In this study, we evaluate the efficacy of FP in women with endometrioma before planned ovarian surgery. A total of 95 cycles in 62 patients with endometrioma, undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin-releasing hormone (GnRH) antagonist protocol before an expected ovarian surgery, were enrolled retrospectively. COS outcomes were compared according to endometrioma laterality. Additionally, first COS cycle outcomes in patients with endometrioma were compared with those in infertile patients, or in patients with a benign ovarian cyst using propensity score matching. When multiple COS cycles were performed, the results of cumulative cycles were analyzed. Embryo quality was worse in the bilateral endometrioma group. Compared with the infertile patient group, the patients with endometrioma had significantly lower Anti-Müllerian Hormone (AMH) and fewer numbers of oocytes retrieved (median, 3.3 vs. 1.2, p & lt;0.001; 7.0 vs. 4.0, p=0.009, respectively). Compared with mature oocytes in infertile patients or patients with a benign cyst, mature oocytes were fewer in patients with endometrioma, but this was not statistically significant (median, 4.0 vs. 3.0, p=0.085; 5.5 vs. 3.0, p=0.052, respectively). The median value of the cumulative number of cryopreserved oocytes or embryos was 14.5 up to the fourth cycle compared to 3 up to the first cycle, with cumulative effect. Women with endometrioma should be counseled for FP before planned ovarian cystectomy. The number of cryopreserved oocytes or embryos can be increased by repeated cycles.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2592084-4
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-2-23)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-2-23)
    Abstract: This study aimed to investigate the usability of blood markers for predicting controlled ovarian stimulation (COS) outcomes in patients with breast cancer undergoing fertility preservation (FP). In total, 91 patients with breast cancer who had undergone COS using a letrozole-combined gonadotropin-releasing hormone (GnRH) antagonist protocol before chemotherapy were enrolled retrospectively in a single tertiary hospital. FP outcomes were compared in terms of the mean platelet volume (MPV), MPV/platelet count (PC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The cutoff values for obtaining 10 or more mature oocytes as favorable prognoses were obtained for each parameter, and the COS outcomes were compared based on the cutoff values. The optimal cutoff levels for MPV and MPV/PC were 10.15 [sensitivity: 90.0%; specificity: 45.1%; AUC: 0.687; 95% CI (0.563, 0.810)] and 0.41 [sensitivity: 65.0%; specificity: 67.6%; AUC: 0.682; 95% CI (0.568, 0.796)], respectively. The oocyte numbers did not significantly differ with respect to the cutoff values of NLR, PLR, and LMR (p & gt; 0.05). However, the total number of acquired and mature oocytes were significantly lower in the group with MPV & lt;10.15 than in that with MPV≥10.15 (8.0 ± 5.1 vs. 12.6 ± 9.1, p=0.003; 4.0 ± 3.7 vs. 7.3 ± 6.3, p=0.002, respectively). Similarly, considering the cutoff of MPV/PC as 0.41, the low-MPV/PC group showed a significantly lower total oocyte yield than the high-MPV/PC group (9.5 ± 7.1 vs. 13.1 ± 9.1, p=0.048), whereas the number of mature oocytes showed similar patterns with no statistical significance (5.3 ± 5.4 vs. 7.3 ± 6.1, p=0.092). From logistic regression analysis, age, anti-Müllerian hormone (AMH) level, MPV, and MPV/PC≥0.41 were found to be significant factors for the acquisition of 10 or more MII oocytes (p=0.049, OR: 0.850; p & lt;0.001, OR: 1.622; p=0.018, OR: 3.184; p=0.013, OR: 9.251, respectively). MPV or MPV/PC can be a reliable marker for predicting FP outcome in patients with breast cancer. Protocols to acquire more mature oocytes, such as the dual-trigger approach, could be recommended for patients with breast cancer with MPV & lt;10.15. Furthermore, a higher dose of gonadotropins was considered to obtain more oocytes in patients with MPV/PC & lt;0.41.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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