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  • Frontiers Media SA  (1,430)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Cellular and Infection Microbiology Vol. 13 ( 2023-3-13)
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 13 ( 2023-3-13)
    Abstract: The gut microbiome has been considered to play an important role in inflammatory bowel disease (IBD). Our previous study reported that tacrolimus-altered gut microbiota elicited immunoregulatory effects in both colonic mucosa and circulation, contributing to an increased allograft survival rate in mice. Here, we aimed to observe the changes in the tacrolimus-induced microbiome in a dextran sulfate sodium (DSS)-induced colitis mouse model and explore the possibility and efficacy of combination therapy with tacrolimus and the microbiome on colitis. Mice were divided into the control, DSS, tacrolimus monotherapy and tacrolimus plus Lactobacillus plantarum 550 ( Lacto )-treated groups. The body weight, stool consistency, hematochezia and survival of mice were observed daily. Total RNA from colonic mucosa was extracted and subjected to transcriptome sequencing. Cecal contents were collected and the 16S rRNA sequencing was performed to characterize the gut microbiome and the ultrahigh- performance liquid chromatography-MS/MS (UHPLC-MS/MS) was used for targeted quantification of bile acids. The results confirmed that tacrolimus significantly ameliorated DSS-induced colitis in mice. Beneficial alterations of the gut microbiome characterized by a remarkable expansion of the genus Lactobacillus were induced by tacrolimus treatment. Oral supplementation with Lacto further improved the tacrolimus-mediated suppression of body weight loss in colitis, while the survival time of mice was further prolonged and the inflammation of colonic mucosa was obviously relieved. The immune and inflammation-related signaling pathways, including IFN-γ and IFN-α response, allograft rejection, IL2 STAT5 signaling and the inflammatory response pathways, were further downregulated in the tacrolimus plus Lacto cotreatment group. Cotreatment also improved the diversity of the gut microbiome and rescued the concentration of taurochenodeoxycholic acid (TCDCA) in colitis. The latter was positively correlated with the abundance of Lactobacillus but negatively related to the disease activity index score. Overall, our results indicated that Lactobacillus plantarum promoted the therapeutic effect of tacrolimus in experimental colitis, offering a promising strategy to combine tacrolimus and Lactobacillus in the treatment of colitis patients.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2619676-1
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  • 2
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2020-9-11)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2649216-7
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  • 3
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-3-29)
    Abstract: Owing to the emergence of drugs targeting human epidermal growth factor receptor 2 (HER2), remarkable prognostic enhancement has been seen for patients with HER2-positive breast carcinoma. However, anti-HER2 medicines are applicable merely to individuals with HER2-positive tumors, and the benefit for those with low HER2 expression is unclear. The DESTINY-Breast04 phase III and RC48 clinical trial results showed the benefit of antibody-drug couples for low HER2-expressing individuals with breast carcinoma, challenging the traditional dichotomy between HER2-negative and -positive tumors. Hence, the purposes of the present work are to explore the clinicopathological traits and prognostic differences in the HER2-low expression Chinese population with early-stage breast carcinoma. Methods Data from the database of the Breast Center of the Affiliated Hospital of Qingdao University were collected from January 2008 to December 2017. We screened a total of 4,598 patients, of which 2,837 had HER2-0 tumors and 1,761 had HER2-low tumors. Additionally, clinicopathological characteristics, survival, and prognostic information were obtained. Difference comparisons were made between HER2-0 and HER2-low groups regarding the clinical traits and outcomes. Results We enrolled 4598 patients, with the HR-positive subjects suffering from HER2-low breast carcinoma higher in proportion than the HR-negative patients. In contrast to HER2-0 tumors, the HER2-low tumors were linked to an older median age at diagnosis, T1 tumors, N1 stage, a higher Ki-67 index, as well as inferior histological grade. Insignificant inter-group difference was noted regarding overall survival (OS), although the HER2–0 group exhibited better disease-free survival (DFS) than the HER2-low group for the entire (P = 0.003), lymph node-negative (P = 0.009) and HR-positive (P = 0.007) populations. According to the multivariate regression finding, low HER2 expression was an inferior DFS prognostic factor in the HER2-negative population with early-stage breast cancer (HR,1.33;95% CI, 1.06-1.66; P = 0.013). Conclusion The clinical traits of the HER2-low carcinomas differed from those of HER2–0 tumors. Despite the insignificant inter-group difference in OS, the differences in DFS were found for the overall, lymph node-negative and HR-positive subjects, suggesting the possibility of HER2-low as an inferior prognostic factor for disease progression in early-stage breast cancer.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 13 ( 2023-1-19)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2023-1-19)
    Abstract: Cyclin-dependent kinases 4 and 6 ( CDK4/6 ) are key regulatory proteins in the cell division and proliferative cycle in humans. They are overactive in many malignant tumors, particularly in triple-negative breast cancer (TNBC). Inhibition of CDK4/6 targets can have anti-tumor effects. Here, we designed and synthesized a novel derivative of Ribociclib that could affect CDK4/6 , named WXJ-202. This study aimed to investigate the effects of compound WXJ-202 on proliferation, apoptosis, and cell cycle arrest in human breast cancer cell lines and their molecular mechanisms. We assayed cell viability with methyl thiazolyl tetrazolium (MTT) assay. Clone formation, migration, and invasion ability were assayed by clone formation assay, wound healing assay, and transwell invasion assay. The effect of compound WXJ-202 on apoptosis and cell cycle was detected by flow cytometry analysis. Western blotting was performed to detect the expression of proteins related to the CDK4/6 - Rb - E2F pathway. The anti-cancer effects were studied in vivo transplantation tumor models. WXJ-202 was shown to inhibit cell proliferation, colony formation, migration, and invasion, as well as induce apoptosis and cycle arrest in breast cancer cells. The levels of proteins related to the CDK4/6 - Rb - E2F pathway, such as CDK4 , CDK6 , and p-Rb , were decreased. Finally, studies had shown that compound WXJ-202 exhibited significant anti-tumor activity in transplantation tumor models. In this research, the compound WXJ-202 was shown to have better anti-tumor cell proliferative effects and could be used as a potential candidate against TNBC tumors.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 5
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-1-26)
    Abstract: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease and has gradually become a public health problem worldwide. DKD is increasingly recognized as a comprehensive inflammatory disease that is largely regulated by T cells. Given the pivotal role of T cells and T cells-producing cytokines in DKD, we summarized recent advances concerning T cells in the progression of type 2 diabetic nephropathy and provided a novel perspective of immune-related factors in diabetes. Specific emphasis is placed on the classification of T cells, process of T cell recruitment, function of T cells in the development of diabetic kidney damage, and potential treatments and therapeutic strategies involving T cells.
    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
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Medicine Vol. 9 ( 2023-1-9)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2023-1-9)
    Abstract: Weill–Marchesani syndrome 4 (WMS4) is caused by ADAMTS17 gene variant and clinical abnormalities including lenticular myopia, ectopia lentis, glaucoma, microspherophakia, brachydactyly, and short stature. Due to free of heart defects and joint stiffness compared with other WMS forms, WMS4 has an insidious onset and is often misdiagnosed as high myopia. We combined multiple imaging biometry and whole-exome sequencing to diagnose a case of WMS4 with a 3-year follow-up. Case presentation An 8-year-old boy presented to our ophthalmology department with progressive myopia for 1 year. He had high myopia in both eyes with normal funds, intraocular pressure, and axial length. Ocular examination revealed thicker lenses (right 4.38 mm, left 4.31 mm) with a smaller equatorial diameter (right 7.33 mm and left 7.17 mm) compared to normal children of the same age. Finger length measurement indicates brachydactyly. Whole-exome sequencing identified compound heterozygous missense variants c.2984G & gt; A (p.Arg995Gln) and c.2254A & gt; G (p.Ile752Val) in the ADAMTS17 gene. During the 3 years of follow-up, the thickness of lenses increased significantly (right 4.49 mm, left 4.48 mm), but the equatorial diameter of the lenses had no significant change (right 7.32 mm, left 7.21 mm). As the equivalent lens power increased, the patient’s myopia spherical refractive error rose accordingly. Although the anterior chamber angle remained open during follow-up, the intraocular pressure increased to right 20.4 mmHg and left 19.6 mmHg, Iridodonesis and short stature were present. Conclusion This case report highlights the abnormal thickening of the lens in WMS4 compared to the physiological thinning process during childhood. Comprehensive clinical examinations and genetic testing may improve diagnosis, which allows early therapeutic interventions for complications and better visual outcomes for the patient.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2775999-4
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Nutrition Vol. 9 ( 2022-9-2)
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 9 ( 2022-9-2)
    Abstract: There is controversy over the optimal energy delivery in intensive care units (ICUs). In this study, we aimed to evaluate the association between different caloric adequacy assessed by a weight-based equation and short-term clinical outcomes in a cohort of critically ill patients. Methods This is a secondary analysis of a cluster-randomized controlled trial ( N = 2,772). The energy requirement was estimated as 25 kcal/kg of body weight. The study subjects were divided into three groups according to their caloric adequacy as calculated by the mean energy delivered from days 3 to 7 of enrollment divided by the estimated energy requirements: (1) received & lt; 70% of energy requirement (hypocaloric), (2) received 70–100% of energy requirement (normocaloric), and (3) received & gt; 100% of energy requirement (hypercaloric). Cox proportional hazards models were used to analyze the association between caloric adequacy and 28-day mortality and time to discharge alive from the ICU. Results A total of 1,694 patients were included. Compared with normocaloric feeding, hypocaloric feeding significantly increased the risk of 28-day mortality (hazard ratio [ HR ] = 1.590, 95% confidence interval [ CI ]: 1.162–2.176, p = 0.004), while hypercaloric feeding did not. After controlling for potential confounders, the association remained valid (adjusted HR = 1.596, 95% CI : 1.150–2.215, p = 0.005). The caloric adequacy was not associated with time to discharge alive from the ICU in the unadjusted and the adjusted models. Conclusion Energy delivery below 70% of the estimated energy requirement during days 3–7 of critical illness is associated with 28-day mortality. Clinical trial registration [ https://www.isrctn.com/ISRCTN12233792 ], identifier [ISRCTN12233792] .
    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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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2024
    In:  Frontiers in Cell and Developmental Biology Vol. 12 ( 2024-6-25)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 12 ( 2024-6-25)
    Abstract: Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear. Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches. Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound–target–pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collagen-induced arthritis (CIA) mouse models. Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis. Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2737824-X
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Genetics Vol. 11 ( 2020-11-27)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 11 ( 2020-11-27)
    Abstract: Anglerfishes are a highly diverse group of species with unique characteristics. Here, we report the first chromosome-level genome of a species in the order Lophiiformes, the yellow goosefish ( Lophius litulon ), obtained by whole genome shotgun sequencing and high-throughput chromatin conformation capture. Approximately 97.20% of the assembly spanning 709.23 Mb could be anchored to 23 chromosomes with a contig N50 of 164.91 kb. The BUSCO value was 95.4%, suggesting that the quality of the assembly was high. A comparative gene family analysis identified expanded and contracted gene families, and these may be associated with adaptation to the benthic environment and the lack of scales in the species. A majority of positively selected genes were related to metabolic processes, suggesting that digestive and metabolic system evolution expanded the diversity of yellow goosefish prey. Our study provides a valuable genetic resource for understanding the mechanisms underlying the unique features of the yellow goosefish and for investigating anglerfish evolution.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606823-0
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Endocrinology Vol. 10 ( 2019-2-4)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 10 ( 2019-2-4)
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2592084-4
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