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  • Frontiers Media SA  (149)
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  • Frontiers Media SA  (149)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-4-29)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-4-29)
    Abstract: Marsdeniae tenacissimae Caulis is a traditional Chinese medicine, named Tongguanteng (TGT), that is often used for the adjuvant treatment of cancer. In our previous study, we reported that an ethyl acetate extract of TGT had inhibitory effects against adenocarcinoma A549 cells growth. To identify the components of TGT with anti-tumor activity and to elucidate their underlying mechanisms of action, we developed a technique for isolating compounds, which was then followed by cytotoxicity screening, network pharmacology analysis, and cellular and molecular experiments. We isolated a total of 19 compounds from a TGT ethyl acetate extract. Two novel steroidal saponins were assessed using an ultra-performance liquid chromatography-photodiode array coupled with quadrupole time-of-flight mass (UPLC-ESI-Q/TOF-MS). Then, we screened these constituents for anti-cancer activity against non-small cell lung cancer (NSCLC) in vitro and obtained six target compounds. Furthermore, a compound-target-pathway network of these six bioactive ingredients was constructed to elucidate the potential pathways that controlled anticancer effects. Approximately 205 putative targets that were associated with TGT, as well as 270 putative targets that were related to NSCLC, were obtained from online databases and target prediction software. Protein–protein interaction networks for drugs as well as disease putative targets were generated, and 18 candidate targets were detected based on topological features. In addition, pathway enrichment analysis was performed to identify related pathways, including PI3K/AKT, VEGF, and EGFR tyrosine kinase inhibitor resistance, which are all related to metabolic processes and intrinsic apoptotic pathways involving reactive oxygen species (ROS). Then, various cellular experiments were conducted to validate drug-target mechanisms that had been predicted using network pharmacology analysis. The experimental results showed the four C21 steroidal saponins could upregulate Bax and downregulate Bcl-2 expression, thereby changing the mitochondrial membrane potential, producing ROS, and releasing cytochrome C, which finally activated caspase-3, caspase-9, and caspase-8, all of which induced apoptosis in A549 cells. In addition, these components also downregulated the expression of MMP-2 and MMP-9 proteins, further weakening their degradation of extracellular matrix components and type IV collagen, and inhibiting the migration and invasion of A549 cells. Our study elucidated the chemical composition and underlying anti-tumor mechanism of TGT , which may be utilized in the treatment of lung cancer.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-19)
    Abstract: Mesenchymal stem cells (MSCs) have important research value and broad application prospects in liver diseases. This study aims to comprehensively review the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in liver diseases from the perspective of bibliometrics, evaluate the clustering evolution of knowledge structure, and discover hot trends and emerging topics. Methods The articles and reviews related to MSCs in liver diseases were retrieved from the Web of Science Core Collection using Topic Search. A bibliometric study was performed using CiteSpace and VOSviewer. Results A total of 3404 articles and reviews were included over the period 2001-2021. The number of articles regarding MSCs in liver diseases showed an increasing trend. These publications mainly come from 3251 institutions in 113 countries led by China and the USA. Li L published the most papers among the publications, while Pittenger MF had the most co-citations. Analysis of the most productive journals shows that most are specialized in medical research, experimental medicine and cell biology, and cell & amp; tissue engineering. The macroscopical sketch and micro-representation of the whole knowledge field are realized through co-citation analysis. Liver scaffold, MSC therapy, extracellular vesicle, and others are current and developing areas of the study. The keywords “machine perfusion”, “liver transplantation”, and “microRNAs” also may be the focus of new trends and future research. Conclusions In this study, bibliometrics and visual methods were used to review the research of MSCs in liver diseases comprehensively. This paper will help scholars better understand the dynamic evolution of the application of MSCs in liver diseases and point out the direction for future research.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Nutrition Vol. 9 ( 2022-9-7)
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 9 ( 2022-9-7)
    Abstract: This study aimed to investigate anemia treatment and other potential effects of two food-derived bioactive oligopeptide iron complexes on pregnant rats with iron deficiency anemia (IDA) and their offspring. Rats with IDA were established with a low iron diet and then mated. There were one control group and seven randomly assigned groups of pregnant rats with IDA: Control group [Control, 40 ppm ferrous sulfate (FeSO 4 )]; IDA model group (ID, 4 ppm FeSO 4 ), three high-iron groups (H-FeSO 4 , 400 ppm FeSO 4 ; MCOP-Fe, 400 ppm marine fish oligopeptide iron complex; WCOP-Fe, 400 ppm whey protein oligopeptide iron complex) and three low-iron groups (L-FeSO 4 , 40 ppm FeSO 4 ; MOP-Fe, 40 ppm marine fish oligopeptide iron complex; WOP-Fe, 40 ppm whey protein oligopeptide iron complex). Rats in each group were fed the corresponding special diet during pregnancy until the day of delivery. After different doses of iron supplement, serum hemoglobin, iron, and ferritin levels in rats with IDA were significantly increased to normal levels ( P & lt; 0.05). Serum iron levels were significantly lower in two food-derived bioactive oligopeptide low-iron complex groups than in the low FeSO 4 group ( P & lt;0.05). Liver malondialdehyde levels were significantly increased in the three high-iron groups compared with the other five groups ( P & lt; 0.05), and hemosiderin deposition was observed in liver tissue, indicating that the iron dose was overloaded and aggravated the peroxidative damage in pregnant rats. Liver inflammation was reduced in the three low-iron groups. Tumor necrosis factor α secretion was significantly decreased in all groups with supplemented oligopeptide ( P & lt; 0.05), with the concentration of tumor necrosis factor α declining to normal levels in the two whey protein oligopeptide iron complex groups. In the marine fish oligopeptide iron complex groups, body length, tail length, and weight of offspring were significantly increased ( P & lt; 0.05) and reached normal levels. Therefore, food-derived bioactive oligopeptide (derived from marine fish skin and milk) iron complexes may be an effective type of iron supplement for pregnancy to improve anemia, as well as reduce the side effects of iron overload, and improve the growth and nutritional status of offspring.
    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 ; 2018
    In:  Frontiers in Immunology Vol. 9 ( 2018-5-31)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 9 ( 2018-5-31)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2606827-8
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  • 5
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-4-25)
    Abstract: The disruption of intestinal barrier functions and the dysregulation of mucosal immune responses, mediated by aberrant purinergic metabolism, are involved in the pathogenesis of inflammatory bowel diseases (IBD). A novel mesenchymal-like endometrial regenerative cells (ERCs) has demonstrated a significant therapeutic effect on colitis. As a phenotypic marker of ERCs, CD73 has been largely neglected for its immunosuppressive function in regulating purinergic metabolism. Here, we have investigated whether CD73 expression on ERCs is a potential molecular exerting its therapeutic effect against colitis. Methods ERCs either unmodified or with CD73 knockout (CD73 -/- ERCs), were intraperitoneally administered to dextran sulfate sodium (DSS)-induced colitis mice. Histopathological analysis, colon barrier function, the proportion of T cells, and maturation of dendritic cells (DCs) were investigated. The immunomodulatory effect of CD73-expressing ERCs was evaluated by co-culture with bone marrow-derived DCs under LPS stimulation. FACS determined DCs maturation. The function of DCs was detected by ELISA and CD4 + cell proliferation assays. Furthermore, the role of the STAT3 pathway in CD73-expressing ERCs-induced DC inhibition was also elucidated. Results Compared with untreated and CD73 -/- ERCs-treated groups, CD73-expressing ERCs effectively attenuated body weight loss, bloody stool, shortening of colon length, and pathological damage characterized by epithelial hyperplasia, goblet cell depletion, the focal loss of crypts and ulceration, and the infiltration of inflammatory cells. Knockout of CD73 impaired ERCs-mediated colon protection. Surprisingly, CD73-expressing ERCs significantly decreased the populations of Th1 and Th17 cells but increased the proportions of Tregs in mouse mesenteric lymph nodes. Furthermore, CD73-expressing ERCs markedly reduced the levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and increased anti-inflammatory factors (IL-10) levels in the colon. CD73-expressing ERCs inhibited the antigen presentation and stimulatory function of DCs associated with the STAT-3 pathway, which exerted a potent therapeutic effect against colitis. Conclusions The knockout of CD73 dramatically abrogates the therapeutic ability of ERCs for intestinal barrier dysfunctions and the dysregulation of mucosal immune responses. This study highlights the significance of CD73 mediates purinergic metabolism contributing to the therapeutic effects of human ERCs against colitis in mice.
    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 ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-3-28)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-3-28)
    Abstract: Background: For anaphylaxis, a life-threatening allergic reaction, the incidence rate was presented to have increased from the beginning of the 21st century. Underdiagnosis and undertreatment of anaphylaxis are public health concerns. Objective: This guideline aimed to provide high-quality and evidence-based recommendations for the emergency management of anaphylaxis. Method: The panel of health professionals from fifteen medical areas selected twenty-five clinical questions and formulated the recommendations with the supervision of four methodologists. We collected evidence by conducting systematic literature retrieval and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: This guideline made twenty-five recommendations that covered the diagnosis, preparation, emergency treatment, and post-emergency management of anaphylaxis. We recommended the use of a set of adapted diagnostic criteria from the American National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network (NIAID/FAAN), and developed a severity grading system that classified anaphylaxis into four grades. We recommended epinephrine as the first-line treatment, with specific doses and routes of administration for different severity of anaphylaxis or different conditions. Proper dosage is critical in the administration of epinephrine, and the monitor is important in the IV administration. Though there was only very low or low-quality evidence supported the use of glucocorticoids and H1 antagonists, we still weakly recommended them as second-line medications. We could not make a well-directed recommendation regarding premedication for preventing anaphylaxis since it is difficult to weigh the concerns and potential effects. Conclusion: For the emergency management of anaphylaxis we conclude that: • NIAID/FAAN diagnostic criteria and the four-tier grading system should be used for the diagnosis • Prompt and proper administration of epinephrine is critical.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Microbiology Vol. 12 ( 2021-7-8)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 12 ( 2021-7-8)
    Abstract: The Toll/interleukin-1 receptor (TIR) domain is a structural unit responsible for the assembly of signal protein complexes in Toll-like receptor (TLR) and interleukin-1 receptor signaling pathways. TIR domain homologs are found in a considerable number of bacteria and enhance bacterial infection and survival in host organisms. However, whether TIR domain homologs exist in Aeromonas hydrophila , a ubiquitous waterborne bacterium in aquatic environments, remains poorly understood. In this study, a TIR domain protein (TcpAh) was identified from A . hydrophila JBN2301. TIR domain of TcpAh is highly homologous to the counterpart domains in TLRs and myeloid differentiation factor 88 (MyD88). The zebrafish infected with mutant A . hydrophila with tcpAh deletion had a remarkably lower mortality than those infected with the wild-type strain. This result suggests that TcpAh is a crucial virulence factor for A . hydrophila infection. TcpAh exhibited a strong ability to associate with MyD88, tumor necrosis factor receptor-associated factor 3 (TRAF3) and TRAF-associated NF-κB activator-binding kinase 1 (TBK1) in TIR–TIR, TIR–Death domain (DD), and other alternative interactions. This finding suggests that TcpAh extensively interferes with MyD88 and TIR domain-containing adapter inducing interferon (IFN)-β (TRIF) signaling pathways downstream of TLRs. Consequently, CD80/86 expression was suppressed by TcpAh via attenuating TLR-stimulated NF-κB activation, which ultimately led to the impairment of the major costimulatory signal essential for the initiation of adaptive humoral immunity against A . hydrophila infection. We believe that this study is the first to show a previously unrecognized mechanism underlying A . hydrophila evades from host antibacterial defense by intervening CD80/86 signal, which bridges innate and adaptive immunity. The mechanism will benefit the development of therapeutic interventions for A . hydrophila infection and septicemia by targeting TcpAh homologs.
    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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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-11-22)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-11-22)
    Abstract: Background: Tripartite motif containing 46 was initially identified as the oncogene in several human tumors. However, the clinical value and potential functions of tripartite motif containing 46 (TRIM46) in clear cell renal cell carcinoma (ccRCC) remained largely unclear. Methods: The expressing patterns, clinical involvement, and prognostic values of TRIM46 were analyzed using the data obtained from TCGA and GEO databases. A nomogram was constructed to examine the outcome of patients with ccRCC. We estimated the association between TRIM46 with tumor immunity in ccRCC. Results: Tripartite motif containing 46 was highly expressed in ccRCC, and its upregulation revealed an unfavorable prognosis. A nomogram based on TRIM46 expressions and other independent prognostic factors could robustly predict the overall survival of tumor patients. TRIM46 has a strong positive correlation with NUMBL, CACNB1, THBS3, ROBO3, MAP3K12, ANKRD13D, PIF1, PRELID3A, ANKRD13B, and PCNX2. Mechanically, TRIM46 displayed regulatory functions in ccRCC progression via several tumor-associated pathways. Besides, we observed that TRIM46 was distinctly related to tumor immunity in ccRCC. Conclusions: Our findings provide a novel tumor promotive role regarding TRIM46 function in the malignant progression of ccRCC.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Cardiovascular Medicine Vol. 10 ( 2023-3-7)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 10 ( 2023-3-7)
    Abstract: Septic shock patients fundamentally require delicate vasoactive and inotropic agent administration, which could be quantitatively and objectively evaluated by the vasoactive–inotropic score (VIS); however, whether the dynamic trends of high-time-resolution VIS alter the clinical outcomes remains unclear. Thus, this study proposes the term VIS Reduction Rate (VRR) to generalise the tendency of dynamic VIS, to explore the association of VRR and mortality for patients with septic shock. Methods We applied dynamic and static VIS data to predict ICU mortality by two models: the long short-term memory (LSTM) deep learning model, and the extreme gradient boosting (XGBoost), respectively. The specific target cohort was extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database by the sophisticated structured query language (SQL). Enrolled patients were divided into four groups by VRR value: ≥50%, 0 ~ 50%, −50% ~ 0, and & lt; −50%. Statistical approaches included pairwise propensity score matching (PSM), Cox proportional hazards regression, and two doubly robust estimation models to ensure the robustness of the results. The primary and secondary outcomes were ICU mortality and in-hospital mortality, respectively. Results VRR simplifies the dosing trends of vasoactive and inotropic agents represented by dynamic VIS data while requiring fewer data. In total, 8,887 septic shock patients were included. Compared with the VRR ≥50% group, the 0 ~ 50%, −50% ~ 0, and  & lt; −50% groups had significantly higher ICU mortality [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.17–1.50, p   & lt; 0.001; HR 1.79, 95% CI 1.44–2.22, p   & lt; 0.001; HR 2.07, 95% CI 1.61–2.66, p   & lt; 0.001, respectively] and in-hospital mortality [HR 1.43, 95% CI 1.28–1.60, p  & lt; 0.001; HR 1.75, 95% CI 1.45–2.11, p   & lt; 0.001; HR 2.00, 95% CI 1.61–2.49, p   & lt; 0.001, respectively]. Similar findings were observed in two doubly robust estimation models. Conclusion The trends of dynamic VIS in ICU might help intensivists to stratify the prognosis of adult patients with septic shock. A lower decline of VIS was remarkably associated with higher ICU and in-hospital mortality among septic shock patients receiving vasoactive–inotropic therapy for more than 24 h.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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  • 10
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-3-18)
    Abstract: The systemic immune-inflammation index, a new index based on platelets, neutrophils and lymphocytes, has been shown to be associated with outcomes of patients with venous sinus thrombosis and cancer. However, its application in acute ischemic stroke has rarely been reported. Therefore, we examined the relationship between systemic immune-inflammation index levels at hospital admission and the outcomes of patients 3 months after onset, and plotted a nomogram to predict the probability of adverse outcomes in patients with acute ischemic stroke. Methods We retrospectively analyzed a total of 208 patients with acute ischemic stroke who were admitted between January 2020 and December 2020, and recorded the modified Rankin score 3 months later. A modified Rankin score ≥ 3 was defined as an adverse outcome. Age, sex, NIHSS score, SII, hypertension and coronary heart disease were included in the binary logistic regression, and the nomogram was plotted with a regression equation. Results Receiver operating characteristic (ROC) curve analysis indicated that the best cutoff value of the systemic immune-inflammation index was 802.8, with a sensitivity of 70.9% and specificity of 58.2% (area under the curve: 0.657, 95% confidence interval: 0.572–0.742). The nomogram had a C index of 0.802. The average error of the calibration curves of the training set and the validation set was 0.021 and 0.034, respectively. Conclusion The systemic immune-inflammation index is associated with short-term adverse outcomes in patients with acute ischemic stroke, and the nomograms can predict the risk of adverse outcomes in patients with acute ischemic stroke.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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